ExonSkipAD: functional annotation of exon skipping event in human

Gene summary for MLH1

Gene summary

Gene information	Gene symbol	MLH1
	Gene ID	4292
	Gene name	mutL homolog 1
	Synonyms	COCA2\|FCC2\|HNPCC\|HNPCC2\|hMLH1
	Cytomap	3p22.2
	Type of gene	protein-coding
	Description	DNA mismatch repair protein Mlh1mutL homolog 1, colon cancer, nonpolyposis type 2
	Modification date	20200327
	UniProtAcc	A0A024R2S9, A0A087WX20, A1YR10, A5JTV0, A5JTV1, A8W2I7, A8W2J0, A8W2J3, A8W2J6, A8W2J9, A8W2K2, A8W2K5, A8W2K8, A8W2L2, A8W2L5, A8W2L8, A8W2M1, C4PFY8, C9JZ54, E7EUC9, E9PF25, F2Z298, H0Y4N0, H0Y5L7, H0Y5U4, H0Y793, H0Y806, H0Y818, L8E8C0, P40692, Q0ZAJ3, Q0ZAJ4, Q0ZAJ5, Q0ZAJ6, Q0ZAJ7, Q0ZAJ8, Q64FK0, Q6VBB8,
	Context

Gene ontology of each this gene with evidence of Inferred from Direct Assay (IDA) from Entrez

Gene

GO ID

GO term

PubMed ID

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Gene structures and expression levels for MLH1

Skipped exons in the ROSMAP, MSBB, and Mayo based on Ensembl gene isoform structure.
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

ENSG00000076242

Differentially expressed gene analysis across multiple brain tissues between AD and control.

Tissue type

DEG direction

Base mean exp.

log2FC(AD/control)

P-value

Adj. p-value

Differentially expressed isoform analysis across multiple brain tissues between AD and control.

Tissue type	DEG direction	ENST	Transcript info.	Base mean exp.	log2FC(AD/control)	P-value	Adjc. p-value
CB	DOWN	ENST00000435176.5	MLH1-206:protein_coding:MLH1	2.306838e+02	-9.511319e-01	1.178406e-06	1.723236e-05

Landscape of isoform expressions across multiple brain tissues between AD and control.

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Exon skipping events with PSIs in ROSMAP, MSBB, and Mayo for MLH1

Landscape of individual exon skipping event across AD tissues and controls (PSI heatmap).

All exon skipping events in AD cohorts.

Exon skip ID	chr	Exons involved in exon skipping	Skipped exon
exon_skip_111773	chr3	36993573:36993663:36996619:36996709:37000955:37001048	36996619:36996709
exon_skip_116836	chr3	37014432:37014544:37017506:37017599:37020310:37020463	37017506:37017599
exon_skip_128177	chr3	37004401:37004474:37006991:37007063:37008814:37008882	37006991:37007063
exon_skip_13651	chr3	37000955:37001053:37004401:37004474:37006991:37007063	37004401:37004474
exon_skip_152286	chr3	37042268:37042331:37047519:37047683:37048517:37048609	37047519:37047683
exon_skip_15448	chr3	36996624:36996709:37000955:37001048:37004401:37004474	37000955:37001048
exon_skip_154665	chr3	37040186:37040294:37042268:37042331:37047519:37047683	37042268:37042331
exon_skip_212802	chr3	37020310:37020463:37025637:37026007:37028784:37028847	37025637:37026007
exon_skip_21826	chr3	36993533:36993663:36996619:36996709:37000955:37001053	36996619:36996709
exon_skip_222060	chr3	37014432:37014544:37020310:37020463:37025637:37025919	37020310:37020463
exon_skip_225811	chr3	36996624:36996709:36997156:36997300:37000955:37001053	36997156:36997300
exon_skip_233995	chr3	37012082:37012099:37014432:37014544:37020310:37020463	37014432:37014544
exon_skip_240160	chr3	36993848:36993890:36994830:36994903:36996619:36996709	36994830:36994903
exon_skip_2546	chr3	37006991:37007063:37008814:37008905:37011820:37011836	37008814:37008905
exon_skip_257062	chr3	37014432:37014544:37017506:37017599:37025637:37026007	37017506:37017599
exon_skip_261889	chr3	36993533:36993663:36996624:36996709:37000955:37001053	36996624:36996709
exon_skip_276751	chr3	37020315:37020463:37025637:37026007:37028784:37028847	37025637:37026007
exon_skip_278434	chr3	36996624:36996709:37000955:37001053:37004401:37004474	37000955:37001053
exon_skip_27940	chr3	36993848:36993890:36994830:36994953:36996619:36996709	36994830:36994953
exon_skip_285564	chr3	37004401:37004474:37005861:37005966:37006991:37007063	37005861:37005966
exon_skip_38692	chr3	37012082:37012099:37014432:37014544:37017506:37017599	37014432:37014544
exon_skip_42741	chr3	37014432:37014544:37017506:37017599:37020310:37020341	37017506:37017599
exon_skip_52060	chr3	37047519:37047683:37048517:37048609:37048904:37049017	37048517:37048609
exon_skip_63005	chr3	37017506:37017599:37020310:37020463:37025637:37026007	37020310:37020463
exon_skip_6587	chr3	36996619:36996709:36997156:36997300:37000955:37001053	36997156:36997300
exon_skip_81769	chr3	36996624:36996709:36997156:36997300:37000955:37001048	36997156:36997300
exon_skip_84295	chr3	36993777:36993890:36994830:36994953:36996619:36996709	36994830:36994953
exon_skip_84458	chr3	36993573:36993663:36996624:36996709:37000955:37001048	36996624:36996709
exon_skip_93862	chr3	37006993:37007063:37008814:37008905:37011820:37011836	37008814:37008905

Differentially expressed PSI values of individual exon skipping events in multiple brain tissues between AD and control.

Exon skipping information

Tissue type

Avg(PSIs) in AD

Avg(PSIs) in control

Difference (PSI)

Adj. p-value

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Open reading frame (ORF) annotation in the exon skipping event for MLH1

Open reading frame (ORF) of individual exon skipping events in ROSMAP based on the Ensembl gene structure combined from isoforms.

ENST	Start of skipped exon	End of skipped exon	ORF
ENST00000231790	37008814	37008905	Frame-shift
ENST00000231790	37014432	37014544	Frame-shift
ENST00000231790	37017506	37017599	Frame-shift
ENST00000231790	37020310	37020463	Frame-shift
ENST00000231790	37025637	37026007	Frame-shift
ENST00000231790	37042268	37042331	Frame-shift
ENST00000231790	37000955	37001053	In-frame
ENST00000231790	37047519	37047683	In-frame
ENST00000231790	37048517	37048609	In-frame

Open reading frame (ORF) of individual exon skipping events in MSBB based on the Ensembl gene structure combined from isoforms.

ENST	Start of skipped exon	End of skipped exon	ORF
ENST00000231790	37008814	37008905	Frame-shift
ENST00000231790	37017506	37017599	Frame-shift
ENST00000231790	37025637	37026007	Frame-shift
ENST00000231790	37042268	37042331	Frame-shift
ENST00000231790	37000955	37001053	In-frame
ENST00000231790	37048517	37048609	In-frame

Open reading frame (ORF) of individual exon skipping events in Mayo based on the Ensembl gene structure combined from isoforms.

ENST	Start of skipped exon	End of skipped exon	ORF
ENST00000231790	37004401	37004474	Frame-shift
ENST00000231790	37006991	37007063	Frame-shift
ENST00000231790	37008814	37008905	Frame-shift
ENST00000231790	37017506	37017599	Frame-shift
ENST00000231790	37025637	37026007	Frame-shift
ENST00000231790	37042268	37042331	Frame-shift
ENST00000231790	37000955	37001053	In-frame
ENST00000231790	37047519	37047683	In-frame
ENST00000231790	37048517	37048609	In-frame

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Infer the effects of exon skipping event on protein functional features for MLH1

p-ENSG00000076242_img4.png
boxplot

Loci of skipped exons in ROSMAP across genomic, transcript, and protein sequence levels of In-frame cases.

ENST	Length of mRNA	Length of AA seq.	Genomic start	Genomic end	mRNA start	mRNA end	AA start	AA end
ENST00000231790	2769	756	37000955	37001053	425	522	69	102
ENST00000231790	2769	756	37047519	37047683	1949	2112	577	632
ENST00000231790	2769	756	37048517	37048609	2114	2205	632	663

Loci of skipped exons in MSBB across genomic, transcript, and protein sequence levels of In-frame cases.

ENST	Length of mRNA	Length of AA seq.	Genomic start	Genomic end	mRNA start	mRNA end	AA start	AA end
ENST00000231790	2769	756	37000955	37001053	425	522	69	102
ENST00000231790	2769	756	37048517	37048609	2114	2205	632	663

Loci of skipped exons in Mayo across genomic, transcript, and protein sequence levels of In-frame cases.

ENST	Length of mRNA	Length of AA seq.	Genomic start	Genomic end	mRNA start	mRNA end	AA start	AA end
ENST00000231790	2769	756	37000955	37001053	425	522	69	102
ENST00000231790	2769	756	37047519	37047683	1949	2112	577	632
ENST00000231790	2769	756	37048517	37048609	2114	2205	632	663

Lost protein functional features of individual exon skipping events in ROSMAP.

UniProt acc.	Start of exon skipping (AA)	End of exon skipping (AA)	Protein feature start (AA)	Protein feature end (AA)	Category of protein feature	Description of feature
P40692	69	102	1	241	Alternative sequence	ID=VSP_045201;Note=In isoform 2. Missing;Ontology_term=ECO:0000303;evidence=ECO:0000303\|PubMed:14702039;Dbxref=PMID:14702039
P40692	69	102	1	101	Alternative sequence	ID=VSP_047023;Note=In isoform 3. MSFVAGVIRRLDETVVNRIAAGEVIQRPANAIKEMIENCLDAKSTSIQVIVKEGGLKLIQIQDNGTGIRKEDLDIVCERFTTSKLQSFEDLASISTYGFRG->MAF;Ontology_term=ECO:0000303;evidence=ECO:0000303\|PubMed:14702039;Dbxref=PMID:14702039
P40692	69	102	2	756	Chain	ID=PRO_0000178000;Note=DNA mismatch repair protein Mlh1
P40692	69	102	70	72	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:4P7A
P40692	69	102	69	69	Natural variant	ID=VAR_004441;Note=In HNPCC2%3B decreased mismatch repair activity. R->K;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:10627141;Dbxref=dbSNP:rs63751661,PMID:10627141
P40692	69	102	71	71	Natural variant	ID=VAR_043393;Note=In HNPCC2%3B decreased mismatch repair activity%3B loss of protein expression. Missing;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:16083711,ECO:0000269\|PubMed:21120944;Dbxref=PMID:16083711,PMID:21120944
P40692	69	102	77	77	Natural variant	ID=VAR_004442;Note=In HNPCC2%3B decreased mismatch repair activity%3B loss of nuclear localization%3B normal interaction with PMS2. C->R;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:10660333,ECO:000
P40692	69	102	77	77	Natural variant	ID=VAR_012904;Note=In CRC%3B sporadic%3B early onset. C->Y;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:9032648;Dbxref=dbSNP:rs63750437,PMID:9032648
P40692	69	102	80	80	Natural variant	ID=VAR_012905;Note=In HNPCC2%3B decreased mismatch repair activity. F->V;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:11726306,ECO:0000269\|PubMed:16083711,ECO:0000269\|PubMed:21120944;Dbxref=dbSNP:rs63749990,PMID:11726306,P
P40692	69	102	84	84	Natural variant	ID=VAR_012906;Note=In HNPCC2%3B decreased mismatch repair activity. K->E;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:10323887,ECO:0000269\|PubMed:16083711,ECO:0000269\|PubMed:21120944;Dbxref=dbSNP:rs63750641,PMID:10323887,P
P40692	69	102	93	93	Natural variant	ID=VAR_004443;Note=Common polymorphism%3B normal interaction with PMS2%3B no decrease in mismatch repair activity%3B no effect on nuclear localization. S->G;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269;
P40692	69	102	98	98	Natural variant	ID=VAR_054523;Note=Associated with HNPCC2%3B no effect on MLH1 splicing. G->S;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:18561205;Dbxref=dbSNP:rs267607725,PMID:18561205
P40692	69	102	101	101	Natural variant	ID=VAR_022664;Note=In HNPCC2%3B no effect on MLH1 splicing. G->D;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:14635101,ECO:0000269\|PubMed:18561205;Dbxref=dbSNP:rs267607727,PMID:14635101,PMID:18561205
P40692	69	102	101	101	Natural variant	ID=VAR_054524;Note=Associated with HNPCC2%3B no effect on MLH1 splicing. G->S;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:18561205;Dbxref=dbSNP:rs267607726,PMID:18561205
P40692	69	102	102	102	Natural variant	ID=VAR_043394;Note=In HNPCC2%3B unknown pathological significance. E->K;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:17510385;Dbxref=dbSNP:rs63750453,PMID:17510385
P40692	69	102	82	84	Nucleotide binding	Note=ATP;Ontology_term=ECO:0000244,ECO:0000305;evidence=ECO:0000244\|PDB:4P7A,ECO:0000305\|PubMed:26249686;Dbxref=PMID:26249686
P40692	69	102	100	104	Nucleotide binding	Note=ATP;Ontology_term=ECO:0000244,ECO:0000305;evidence=ECO:0000244\|PDB:4P7A,ECO:0000305\|PubMed:26249686;Dbxref=PMID:26249686
P40692	69	102	73	77	Turn	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:4P7A
P40692	577	632	572	581	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3RBN
P40692	577	632	2	756	Chain	ID=PRO_0000178000;Note=DNA mismatch repair protein Mlh1
P40692	577	632	582	590	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3RBN
P40692	577	632	593	595	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3RBN
P40692	577	632	604	626	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3RBN
P40692	577	632	578	632	Natural variant	ID=VAR_076348;Note=In HNPCC2%3B decreased mismatch repair activity%3B defective in interaction with PMS2. Missing;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:21120944;Dbxref=PMID:21120944
P40692	577	632	578	578	Natural variant	ID=VAR_004459;Note=In HNPCC2 and CRC%3B unknown pathological significance%3B no decrease in mismatch repair activity%3B no effect on nuclear localization. E->G;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:10598809,ECO:0000
P40692	577	632	582	582	Natural variant	ID=VAR_076349;Note=In HNPCC2%3B decreased mismatch repair activity%3B no effect on nuclear localization. L->F;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:20020535,ECO:0000269\|PubMed:22753075;Dbxref=dbSNP:rs63751713,PMID:20020535,PMID
P40692	577	632	582	582	Natural variant	ID=VAR_004460;Note=In HNPCC2%3B type II. L->V;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:7757073;Dbxref=dbSNP:rs63751713,PMID:7757073
P40692	577	632	585	585	Natural variant	ID=VAR_054534;Note=Associated with HNPCC2%3B no effect on MLH1 splicing. L->R;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:18561205;Dbxref=dbSNP:rs267607865,PMID:18561205
P40692	577	632	586	586	Natural variant	ID=VAR_015689;Note=In HNPCC2. A->P;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:12655562;Dbxref=dbSNP:rs63751176,PMID:12655562
P40692	577	632	588	588	Natural variant	ID=VAR_012924;Note=In HNPCC2. L->P;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:10777691;Dbxref=dbSNP:rs63750575,PMID:10777691
P40692	577	632	589	589	Natural variant	ID=VAR_043419;Note=In HNPCC2%3B decreased mismatch repair activity%3B loss of interaction with PMS2 and EXO1%3B loss of protein expression%3B may lose nuclear localization. A->D;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:00
P40692	577	632	596	596	Natural variant	ID=VAR_043420;Note=In HNPCC2. Missing
P40692	577	632	601	601	Natural variant	ID=VAR_043421;Note=In CRC%3B unknown pathological significance. D->G;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:12655564;Dbxref=dbSNP:rs63750718,PMID:12655564
P40692	577	632	603	603	Natural variant	ID=VAR_012925;Note=In HNPCC2%3B unknown pathological significance%3B no effect on MLH1 splicing. P->R;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:11726306,ECO:0000269\|PubMed:12095971,ECO:0000269\|PubMed:18561205;Dbxref=dbS
P40692	577	632	607	607	Natural variant	ID=VAR_012926;Note=In HNPCC2%3B unknown pathological significance%3B also found in lobular carcinoma in situ of the breast%3B no effect on MLH1 splicing. L->H;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269\|P
P40692	577	632	612	612	Natural variant	ID=VAR_043422;Note=In HNPCC2%3B loss of protein expression%3B loss of nuclear localization. Missing;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:16083711,ECO:0000269\|PubMed:21120944;Dbxref=PMID:16083711,PMID:21120944
P40692	577	632	616	616	Natural variant	ID=VAR_004461;Note=In HNPCC2 and MMRCS%3B abrogates interaction with EXO1%3B loss of protein expression%3B loss of nuclear localization%3B no effect on MLH1 splicing. Missing;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:00
P40692	577	632	618	618	Natural variant	ID=VAR_004462;Note=In HNPCC2%3B unknown pathological significance%3B requires 2 nucleotide substitutions%3B interacts weakly with PMS2%3B no decrease in mismatch repair activity%3B no effect on nuclear localization. K->A;Ontology_term=ECO:0000269,ECO:0000
P40692	577	632	618	618	Natural variant	ID=VAR_043424;Note=In CRC. K->R;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:14504054;Dbxref=dbSNP:rs63750449,PMID:14504054
P40692	577	632	618	618	Natural variant	ID=VAR_004463;Note=In HNPCC2%3B type II%3B loss of nuclear localization. K->T;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:10573010,ECO:0000269\|PubMed:11839723,ECO:0000269\|Pu
P40692	577	632	618	618	Natural variant	ID=VAR_043423;Note=In HNPCC2. Missing;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:16451135;Dbxref=PMID:16451135
P40692	577	632	619	619	Natural variant	ID=VAR_054535;Note=Associated with HNPCC2%3B no effect on MLH1 splicing. A->P;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:18561205;Dbxref=dbSNP:rs267607866,PMID:18561205
P40692	577	632	622	622	Natural variant	ID=VAR_012927;Note=In HNPCC2. L->H;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:11748856;Dbxref=dbSNP:rs63750693,PMID:11748856
P40692	577	632	623	623	Natural variant	ID=VAR_043425;Note=In HNPCC2%3B unknown pathological significance. A->P;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:16451135;Dbxref=PMID:16451135
P40692	577	632	626	627	Natural variant	ID=VAR_004464;Note=In HNPCC2. FS->ST
P40692	577	632	631	631	Natural variant	ID=VAR_043426;Note=In HNPCC2%3B unknown pathological significance. D->A;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:12132870;Dbxref=dbSNP:rs63750240,PMID:12132870
P40692	577	632	410	650	Region	Note=Interaction with EXO1;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:11427529,ECO:0000269\|PubMed:11429708,ECO:0000269\|PubMed:12414623,ECO:0000269\|PubMed:14676842,ECO:0000269\|PubMed:22753075;Dbxre
P40692	632	663	634	641	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3RBN
P40692	632	663	2	756	Chain	ID=PRO_0000178000;Note=DNA mismatch repair protein Mlh1
P40692	632	663	650	652	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3RBN
P40692	632	663	653	662	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3RBN
P40692	632	663	578	632	Natural variant	ID=VAR_076348;Note=In HNPCC2%3B decreased mismatch repair activity%3B defective in interaction with PMS2. Missing;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:21120944;Dbxref=PMID:21120944
P40692	632	663	633	663	Natural variant	ID=VAR_076350;Note=In HNPCC2%3B decreased mismatch repair activity%3B defective in interaction with PMS2%3B loss of protein expression%3B loss of nuclear localization. Missing;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:21120944;Dbxref=PMID:2112
P40692	632	663	635	635	Natural variant	ID=VAR_043427;Note=In gastric cancer%3B unknown pathological significance. N->K;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:12132870;Dbxref=dbSNP:rs63751047,PMID:12132870
P40692	632	663	636	636	Natural variant	ID=VAR_043428;Note=In HNPCC2. L->P;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:15365995;Dbxref=dbSNP:rs63750825,PMID:15365995
P40692	632	663	640	640	Natural variant	ID=VAR_054536;Note=Associated with HNPCC2%3B no effect on MLH1 splicing. P->L;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:18561205;Dbxref=dbSNP:rs267607875,PMID:18561205
P40692	632	663	640	640	Natural variant	ID=VAR_043429;Note=In HNPCC2%3B no effect on MLH1 splicing. P->S;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:15365995,ECO:0000269\|PubMed:18561205;Dbxref=dbSNP:rs63749792,PMID:15365995,PMID:18561205
P40692	632	663	646	646	Natural variant	ID=VAR_043430;Note=In HNPCC2%3B defective in interaction with PMS2 and EXO1%3B no decrease in mismatch repair activity. Y->C;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:11870161,ECO:0000269\|PubMed:
P40692	632	663	648	648	Natural variant	ID=VAR_012928;Note=In HNPCC2%3B unknown pathological significance%3B defective in interaction with PMS2 and EXO1%3B may lose nuclear localization%3B loss of protein expression%3B no decrease in mismatch repair activity. P->L;Ontology_term=ECO:0000269,ECO:
P40692	632	663	648	648	Natural variant	ID=VAR_022669;Note=In HNPCC2%3B the protein is unstable%3B loss of nuclear localization%3B loss of protein expression%3B no decrease in mismatch repair activity. P->S;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMe
P40692	632	663	654	654	Natural variant	ID=VAR_043431;Note=In HNPCC2%3B decreased mismatch repair activity%3B defective in interaction with PMS2 and EXO1%3B loss of protein expression%3B may lose nuclear localization. P->L;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269;evidence=E
P40692	632	663	655	655	Natural variant	ID=VAR_043432;Note=In HNPCC2%3B also found in an endometrial cancer sample%3B no effect on MLH1 splicing. I->V;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:12115348,ECO:0000269\|PubMed:18561205;Dbxref=dbSNP:rs55907433,PMID:12115348,PMI
P40692	632	663	656	656	Natural variant	ID=VAR_054537;Note=In HNPCC2%3B no effect on MLH1 splicing. F->S;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:18561205;Dbxref=dbSNP:rs267607876,PMID:18561205
P40692	632	663	657	657	Natural variant	ID=VAR_043433;Note=In HNPCC2%3B unknown pathological significance. Missing;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:16451135;Dbxref=PMID:16451135
P40692	632	663	659	659	Natural variant	ID=VAR_012929;Note=In HNPCC2. R->L;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:10713887,ECO:0000269\|PubMed:11427529;Dbxref=dbSNP:rs63749900,PMID:10713887,PMID:11427529
P40692	632	663	659	659	Natural variant	ID=VAR_004465;Note=In HNPCC2%3B interacts only very weakly with PMS2%3B abrogates interaction with EXO1%3B decreased mismatch repair activity%3B may lose nuclear localization. R->P;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,
P40692	632	663	659	659	Natural variant	ID=VAR_043434;Note=In HNPCC2%3B unknown pathological significance. R->Q;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:16083711,ECO:0000269\|PubMed:21120944;Dbxref=dbSNP:rs63749900,PMID:16083711,PMID:21120944
P40692	632	663	662	662	Natural variant	ID=VAR_012930;Note=In HNPCC2%3B unknown pathological significance. T->P;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:11726306,ECO:0000269\|PubMed:11754112;Dbxref=dbSNP:rs587778964,PMID:11726306,PMID:11754112
P40692	632	663	410	650	Region	Note=Interaction with EXO1;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:11427529,ECO:0000269\|PubMed:11429708,ECO:0000269\|PubMed:12414623,ECO:0000269\|PubMed:14676842,ECO:0000269\|PubMed:22753075;Dbxre

Lost protein functional features of individual exon skipping events in MSBB.

UniProt acc.	Start of exon skipping (AA)	End of exon skipping (AA)	Protein feature start (AA)	Protein feature end (AA)	Category of protein feature	Description of feature
P40692	69	102	1	241	Alternative sequence	ID=VSP_045201;Note=In isoform 2. Missing;Ontology_term=ECO:0000303;evidence=ECO:0000303\|PubMed:14702039;Dbxref=PMID:14702039
P40692	69	102	1	101	Alternative sequence	ID=VSP_047023;Note=In isoform 3. MSFVAGVIRRLDETVVNRIAAGEVIQRPANAIKEMIENCLDAKSTSIQVIVKEGGLKLIQIQDNGTGIRKEDLDIVCERFTTSKLQSFEDLASISTYGFRG->MAF;Ontology_term=ECO:0000303;evidence=ECO:0000303\|PubMed:14702039;Dbxref=PMID:14702039
P40692	69	102	2	756	Chain	ID=PRO_0000178000;Note=DNA mismatch repair protein Mlh1
P40692	69	102	70	72	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:4P7A
P40692	69	102	69	69	Natural variant	ID=VAR_004441;Note=In HNPCC2%3B decreased mismatch repair activity. R->K;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:10627141;Dbxref=dbSNP:rs63751661,PMID:10627141
P40692	69	102	71	71	Natural variant	ID=VAR_043393;Note=In HNPCC2%3B decreased mismatch repair activity%3B loss of protein expression. Missing;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:16083711,ECO:0000269\|PubMed:21120944;Dbxref=PMID:16083711,PMID:21120944
P40692	69	102	77	77	Natural variant	ID=VAR_004442;Note=In HNPCC2%3B decreased mismatch repair activity%3B loss of nuclear localization%3B normal interaction with PMS2. C->R;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:10660333,ECO:000
P40692	69	102	77	77	Natural variant	ID=VAR_012904;Note=In CRC%3B sporadic%3B early onset. C->Y;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:9032648;Dbxref=dbSNP:rs63750437,PMID:9032648
P40692	69	102	80	80	Natural variant	ID=VAR_012905;Note=In HNPCC2%3B decreased mismatch repair activity. F->V;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:11726306,ECO:0000269\|PubMed:16083711,ECO:0000269\|PubMed:21120944;Dbxref=dbSNP:rs63749990,PMID:11726306,P
P40692	69	102	84	84	Natural variant	ID=VAR_012906;Note=In HNPCC2%3B decreased mismatch repair activity. K->E;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:10323887,ECO:0000269\|PubMed:16083711,ECO:0000269\|PubMed:21120944;Dbxref=dbSNP:rs63750641,PMID:10323887,P
P40692	69	102	93	93	Natural variant	ID=VAR_004443;Note=Common polymorphism%3B normal interaction with PMS2%3B no decrease in mismatch repair activity%3B no effect on nuclear localization. S->G;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269;
P40692	69	102	98	98	Natural variant	ID=VAR_054523;Note=Associated with HNPCC2%3B no effect on MLH1 splicing. G->S;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:18561205;Dbxref=dbSNP:rs267607725,PMID:18561205
P40692	69	102	101	101	Natural variant	ID=VAR_022664;Note=In HNPCC2%3B no effect on MLH1 splicing. G->D;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:14635101,ECO:0000269\|PubMed:18561205;Dbxref=dbSNP:rs267607727,PMID:14635101,PMID:18561205
P40692	69	102	101	101	Natural variant	ID=VAR_054524;Note=Associated with HNPCC2%3B no effect on MLH1 splicing. G->S;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:18561205;Dbxref=dbSNP:rs267607726,PMID:18561205
P40692	69	102	102	102	Natural variant	ID=VAR_043394;Note=In HNPCC2%3B unknown pathological significance. E->K;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:17510385;Dbxref=dbSNP:rs63750453,PMID:17510385
P40692	69	102	82	84	Nucleotide binding	Note=ATP;Ontology_term=ECO:0000244,ECO:0000305;evidence=ECO:0000244\|PDB:4P7A,ECO:0000305\|PubMed:26249686;Dbxref=PMID:26249686
P40692	69	102	100	104	Nucleotide binding	Note=ATP;Ontology_term=ECO:0000244,ECO:0000305;evidence=ECO:0000244\|PDB:4P7A,ECO:0000305\|PubMed:26249686;Dbxref=PMID:26249686
P40692	69	102	73	77	Turn	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:4P7A
P40692	632	663	634	641	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3RBN
P40692	632	663	2	756	Chain	ID=PRO_0000178000;Note=DNA mismatch repair protein Mlh1
P40692	632	663	650	652	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3RBN
P40692	632	663	653	662	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3RBN
P40692	632	663	578	632	Natural variant	ID=VAR_076348;Note=In HNPCC2%3B decreased mismatch repair activity%3B defective in interaction with PMS2. Missing;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:21120944;Dbxref=PMID:21120944
P40692	632	663	633	663	Natural variant	ID=VAR_076350;Note=In HNPCC2%3B decreased mismatch repair activity%3B defective in interaction with PMS2%3B loss of protein expression%3B loss of nuclear localization. Missing;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:21120944;Dbxref=PMID:2112
P40692	632	663	635	635	Natural variant	ID=VAR_043427;Note=In gastric cancer%3B unknown pathological significance. N->K;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:12132870;Dbxref=dbSNP:rs63751047,PMID:12132870
P40692	632	663	636	636	Natural variant	ID=VAR_043428;Note=In HNPCC2. L->P;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:15365995;Dbxref=dbSNP:rs63750825,PMID:15365995
P40692	632	663	640	640	Natural variant	ID=VAR_054536;Note=Associated with HNPCC2%3B no effect on MLH1 splicing. P->L;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:18561205;Dbxref=dbSNP:rs267607875,PMID:18561205
P40692	632	663	640	640	Natural variant	ID=VAR_043429;Note=In HNPCC2%3B no effect on MLH1 splicing. P->S;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:15365995,ECO:0000269\|PubMed:18561205;Dbxref=dbSNP:rs63749792,PMID:15365995,PMID:18561205
P40692	632	663	646	646	Natural variant	ID=VAR_043430;Note=In HNPCC2%3B defective in interaction with PMS2 and EXO1%3B no decrease in mismatch repair activity. Y->C;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:11870161,ECO:0000269\|PubMed:
P40692	632	663	648	648	Natural variant	ID=VAR_012928;Note=In HNPCC2%3B unknown pathological significance%3B defective in interaction with PMS2 and EXO1%3B may lose nuclear localization%3B loss of protein expression%3B no decrease in mismatch repair activity. P->L;Ontology_term=ECO:0000269,ECO:
P40692	632	663	648	648	Natural variant	ID=VAR_022669;Note=In HNPCC2%3B the protein is unstable%3B loss of nuclear localization%3B loss of protein expression%3B no decrease in mismatch repair activity. P->S;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMe
P40692	632	663	654	654	Natural variant	ID=VAR_043431;Note=In HNPCC2%3B decreased mismatch repair activity%3B defective in interaction with PMS2 and EXO1%3B loss of protein expression%3B may lose nuclear localization. P->L;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269;evidence=E
P40692	632	663	655	655	Natural variant	ID=VAR_043432;Note=In HNPCC2%3B also found in an endometrial cancer sample%3B no effect on MLH1 splicing. I->V;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:12115348,ECO:0000269\|PubMed:18561205;Dbxref=dbSNP:rs55907433,PMID:12115348,PMI
P40692	632	663	656	656	Natural variant	ID=VAR_054537;Note=In HNPCC2%3B no effect on MLH1 splicing. F->S;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:18561205;Dbxref=dbSNP:rs267607876,PMID:18561205
P40692	632	663	657	657	Natural variant	ID=VAR_043433;Note=In HNPCC2%3B unknown pathological significance. Missing;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:16451135;Dbxref=PMID:16451135
P40692	632	663	659	659	Natural variant	ID=VAR_012929;Note=In HNPCC2. R->L;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:10713887,ECO:0000269\|PubMed:11427529;Dbxref=dbSNP:rs63749900,PMID:10713887,PMID:11427529
P40692	632	663	659	659	Natural variant	ID=VAR_004465;Note=In HNPCC2%3B interacts only very weakly with PMS2%3B abrogates interaction with EXO1%3B decreased mismatch repair activity%3B may lose nuclear localization. R->P;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,
P40692	632	663	659	659	Natural variant	ID=VAR_043434;Note=In HNPCC2%3B unknown pathological significance. R->Q;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:16083711,ECO:0000269\|PubMed:21120944;Dbxref=dbSNP:rs63749900,PMID:16083711,PMID:21120944
P40692	632	663	662	662	Natural variant	ID=VAR_012930;Note=In HNPCC2%3B unknown pathological significance. T->P;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:11726306,ECO:0000269\|PubMed:11754112;Dbxref=dbSNP:rs587778964,PMID:11726306,PMID:11754112
P40692	632	663	410	650	Region	Note=Interaction with EXO1;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:11427529,ECO:0000269\|PubMed:11429708,ECO:0000269\|PubMed:12414623,ECO:0000269\|PubMed:14676842,ECO:0000269\|PubMed:22753075;Dbxre

Lost protein functional features of individual exon skipping events in Mayo.

UniProt acc.	Start of exon skipping (AA)	End of exon skipping (AA)	Protein feature start (AA)	Protein feature end (AA)	Category of protein feature	Description of feature
P40692	69	102	1	241	Alternative sequence	ID=VSP_045201;Note=In isoform 2. Missing;Ontology_term=ECO:0000303;evidence=ECO:0000303\|PubMed:14702039;Dbxref=PMID:14702039
P40692	69	102	1	101	Alternative sequence	ID=VSP_047023;Note=In isoform 3. MSFVAGVIRRLDETVVNRIAAGEVIQRPANAIKEMIENCLDAKSTSIQVIVKEGGLKLIQIQDNGTGIRKEDLDIVCERFTTSKLQSFEDLASISTYGFRG->MAF;Ontology_term=ECO:0000303;evidence=ECO:0000303\|PubMed:14702039;Dbxref=PMID:14702039
P40692	69	102	2	756	Chain	ID=PRO_0000178000;Note=DNA mismatch repair protein Mlh1
P40692	69	102	70	72	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:4P7A
P40692	69	102	69	69	Natural variant	ID=VAR_004441;Note=In HNPCC2%3B decreased mismatch repair activity. R->K;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:10627141;Dbxref=dbSNP:rs63751661,PMID:10627141
P40692	69	102	71	71	Natural variant	ID=VAR_043393;Note=In HNPCC2%3B decreased mismatch repair activity%3B loss of protein expression. Missing;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:16083711,ECO:0000269\|PubMed:21120944;Dbxref=PMID:16083711,PMID:21120944
P40692	69	102	77	77	Natural variant	ID=VAR_004442;Note=In HNPCC2%3B decreased mismatch repair activity%3B loss of nuclear localization%3B normal interaction with PMS2. C->R;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:10660333,ECO:000
P40692	69	102	77	77	Natural variant	ID=VAR_012904;Note=In CRC%3B sporadic%3B early onset. C->Y;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:9032648;Dbxref=dbSNP:rs63750437,PMID:9032648
P40692	69	102	80	80	Natural variant	ID=VAR_012905;Note=In HNPCC2%3B decreased mismatch repair activity. F->V;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:11726306,ECO:0000269\|PubMed:16083711,ECO:0000269\|PubMed:21120944;Dbxref=dbSNP:rs63749990,PMID:11726306,P
P40692	69	102	84	84	Natural variant	ID=VAR_012906;Note=In HNPCC2%3B decreased mismatch repair activity. K->E;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:10323887,ECO:0000269\|PubMed:16083711,ECO:0000269\|PubMed:21120944;Dbxref=dbSNP:rs63750641,PMID:10323887,P
P40692	69	102	93	93	Natural variant	ID=VAR_004443;Note=Common polymorphism%3B normal interaction with PMS2%3B no decrease in mismatch repair activity%3B no effect on nuclear localization. S->G;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269;
P40692	69	102	98	98	Natural variant	ID=VAR_054523;Note=Associated with HNPCC2%3B no effect on MLH1 splicing. G->S;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:18561205;Dbxref=dbSNP:rs267607725,PMID:18561205
P40692	69	102	101	101	Natural variant	ID=VAR_022664;Note=In HNPCC2%3B no effect on MLH1 splicing. G->D;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:14635101,ECO:0000269\|PubMed:18561205;Dbxref=dbSNP:rs267607727,PMID:14635101,PMID:18561205
P40692	69	102	101	101	Natural variant	ID=VAR_054524;Note=Associated with HNPCC2%3B no effect on MLH1 splicing. G->S;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:18561205;Dbxref=dbSNP:rs267607726,PMID:18561205
P40692	69	102	102	102	Natural variant	ID=VAR_043394;Note=In HNPCC2%3B unknown pathological significance. E->K;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:17510385;Dbxref=dbSNP:rs63750453,PMID:17510385
P40692	69	102	82	84	Nucleotide binding	Note=ATP;Ontology_term=ECO:0000244,ECO:0000305;evidence=ECO:0000244\|PDB:4P7A,ECO:0000305\|PubMed:26249686;Dbxref=PMID:26249686
P40692	69	102	100	104	Nucleotide binding	Note=ATP;Ontology_term=ECO:0000244,ECO:0000305;evidence=ECO:0000244\|PDB:4P7A,ECO:0000305\|PubMed:26249686;Dbxref=PMID:26249686
P40692	69	102	73	77	Turn	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:4P7A
P40692	577	632	572	581	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3RBN
P40692	577	632	2	756	Chain	ID=PRO_0000178000;Note=DNA mismatch repair protein Mlh1
P40692	577	632	582	590	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3RBN
P40692	577	632	593	595	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3RBN
P40692	577	632	604	626	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3RBN
P40692	577	632	578	632	Natural variant	ID=VAR_076348;Note=In HNPCC2%3B decreased mismatch repair activity%3B defective in interaction with PMS2. Missing;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:21120944;Dbxref=PMID:21120944
P40692	577	632	578	578	Natural variant	ID=VAR_004459;Note=In HNPCC2 and CRC%3B unknown pathological significance%3B no decrease in mismatch repair activity%3B no effect on nuclear localization. E->G;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:10598809,ECO:0000
P40692	577	632	582	582	Natural variant	ID=VAR_076349;Note=In HNPCC2%3B decreased mismatch repair activity%3B no effect on nuclear localization. L->F;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:20020535,ECO:0000269\|PubMed:22753075;Dbxref=dbSNP:rs63751713,PMID:20020535,PMID
P40692	577	632	582	582	Natural variant	ID=VAR_004460;Note=In HNPCC2%3B type II. L->V;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:7757073;Dbxref=dbSNP:rs63751713,PMID:7757073
P40692	577	632	585	585	Natural variant	ID=VAR_054534;Note=Associated with HNPCC2%3B no effect on MLH1 splicing. L->R;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:18561205;Dbxref=dbSNP:rs267607865,PMID:18561205
P40692	577	632	586	586	Natural variant	ID=VAR_015689;Note=In HNPCC2. A->P;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:12655562;Dbxref=dbSNP:rs63751176,PMID:12655562
P40692	577	632	588	588	Natural variant	ID=VAR_012924;Note=In HNPCC2. L->P;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:10777691;Dbxref=dbSNP:rs63750575,PMID:10777691
P40692	577	632	589	589	Natural variant	ID=VAR_043419;Note=In HNPCC2%3B decreased mismatch repair activity%3B loss of interaction with PMS2 and EXO1%3B loss of protein expression%3B may lose nuclear localization. A->D;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:00
P40692	577	632	596	596	Natural variant	ID=VAR_043420;Note=In HNPCC2. Missing
P40692	577	632	601	601	Natural variant	ID=VAR_043421;Note=In CRC%3B unknown pathological significance. D->G;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:12655564;Dbxref=dbSNP:rs63750718,PMID:12655564
P40692	577	632	603	603	Natural variant	ID=VAR_012925;Note=In HNPCC2%3B unknown pathological significance%3B no effect on MLH1 splicing. P->R;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:11726306,ECO:0000269\|PubMed:12095971,ECO:0000269\|PubMed:18561205;Dbxref=dbS
P40692	577	632	607	607	Natural variant	ID=VAR_012926;Note=In HNPCC2%3B unknown pathological significance%3B also found in lobular carcinoma in situ of the breast%3B no effect on MLH1 splicing. L->H;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269\|P
P40692	577	632	612	612	Natural variant	ID=VAR_043422;Note=In HNPCC2%3B loss of protein expression%3B loss of nuclear localization. Missing;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:16083711,ECO:0000269\|PubMed:21120944;Dbxref=PMID:16083711,PMID:21120944
P40692	577	632	616	616	Natural variant	ID=VAR_004461;Note=In HNPCC2 and MMRCS%3B abrogates interaction with EXO1%3B loss of protein expression%3B loss of nuclear localization%3B no effect on MLH1 splicing. Missing;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:00
P40692	577	632	618	618	Natural variant	ID=VAR_004462;Note=In HNPCC2%3B unknown pathological significance%3B requires 2 nucleotide substitutions%3B interacts weakly with PMS2%3B no decrease in mismatch repair activity%3B no effect on nuclear localization. K->A;Ontology_term=ECO:0000269,ECO:0000
P40692	577	632	618	618	Natural variant	ID=VAR_043424;Note=In CRC. K->R;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:14504054;Dbxref=dbSNP:rs63750449,PMID:14504054
P40692	577	632	618	618	Natural variant	ID=VAR_004463;Note=In HNPCC2%3B type II%3B loss of nuclear localization. K->T;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:10573010,ECO:0000269\|PubMed:11839723,ECO:0000269\|Pu
P40692	577	632	618	618	Natural variant	ID=VAR_043423;Note=In HNPCC2. Missing;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:16451135;Dbxref=PMID:16451135
P40692	577	632	619	619	Natural variant	ID=VAR_054535;Note=Associated with HNPCC2%3B no effect on MLH1 splicing. A->P;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:18561205;Dbxref=dbSNP:rs267607866,PMID:18561205
P40692	577	632	622	622	Natural variant	ID=VAR_012927;Note=In HNPCC2. L->H;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:11748856;Dbxref=dbSNP:rs63750693,PMID:11748856
P40692	577	632	623	623	Natural variant	ID=VAR_043425;Note=In HNPCC2%3B unknown pathological significance. A->P;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:16451135;Dbxref=PMID:16451135
P40692	577	632	626	627	Natural variant	ID=VAR_004464;Note=In HNPCC2. FS->ST
P40692	577	632	631	631	Natural variant	ID=VAR_043426;Note=In HNPCC2%3B unknown pathological significance. D->A;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:12132870;Dbxref=dbSNP:rs63750240,PMID:12132870
P40692	577	632	410	650	Region	Note=Interaction with EXO1;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:11427529,ECO:0000269\|PubMed:11429708,ECO:0000269\|PubMed:12414623,ECO:0000269\|PubMed:14676842,ECO:0000269\|PubMed:22753075;Dbxre
P40692	632	663	634	641	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3RBN
P40692	632	663	2	756	Chain	ID=PRO_0000178000;Note=DNA mismatch repair protein Mlh1
P40692	632	663	650	652	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3RBN
P40692	632	663	653	662	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:3RBN
P40692	632	663	578	632	Natural variant	ID=VAR_076348;Note=In HNPCC2%3B decreased mismatch repair activity%3B defective in interaction with PMS2. Missing;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:21120944;Dbxref=PMID:21120944
P40692	632	663	633	663	Natural variant	ID=VAR_076350;Note=In HNPCC2%3B decreased mismatch repair activity%3B defective in interaction with PMS2%3B loss of protein expression%3B loss of nuclear localization. Missing;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:21120944;Dbxref=PMID:2112
P40692	632	663	635	635	Natural variant	ID=VAR_043427;Note=In gastric cancer%3B unknown pathological significance. N->K;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:12132870;Dbxref=dbSNP:rs63751047,PMID:12132870
P40692	632	663	636	636	Natural variant	ID=VAR_043428;Note=In HNPCC2. L->P;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:15365995;Dbxref=dbSNP:rs63750825,PMID:15365995
P40692	632	663	640	640	Natural variant	ID=VAR_054536;Note=Associated with HNPCC2%3B no effect on MLH1 splicing. P->L;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:18561205;Dbxref=dbSNP:rs267607875,PMID:18561205
P40692	632	663	640	640	Natural variant	ID=VAR_043429;Note=In HNPCC2%3B no effect on MLH1 splicing. P->S;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:15365995,ECO:0000269\|PubMed:18561205;Dbxref=dbSNP:rs63749792,PMID:15365995,PMID:18561205
P40692	632	663	646	646	Natural variant	ID=VAR_043430;Note=In HNPCC2%3B defective in interaction with PMS2 and EXO1%3B no decrease in mismatch repair activity. Y->C;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:11870161,ECO:0000269\|PubMed:
P40692	632	663	648	648	Natural variant	ID=VAR_012928;Note=In HNPCC2%3B unknown pathological significance%3B defective in interaction with PMS2 and EXO1%3B may lose nuclear localization%3B loss of protein expression%3B no decrease in mismatch repair activity. P->L;Ontology_term=ECO:0000269,ECO:
P40692	632	663	648	648	Natural variant	ID=VAR_022669;Note=In HNPCC2%3B the protein is unstable%3B loss of nuclear localization%3B loss of protein expression%3B no decrease in mismatch repair activity. P->S;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMe
P40692	632	663	654	654	Natural variant	ID=VAR_043431;Note=In HNPCC2%3B decreased mismatch repair activity%3B defective in interaction with PMS2 and EXO1%3B loss of protein expression%3B may lose nuclear localization. P->L;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269;evidence=E
P40692	632	663	655	655	Natural variant	ID=VAR_043432;Note=In HNPCC2%3B also found in an endometrial cancer sample%3B no effect on MLH1 splicing. I->V;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:12115348,ECO:0000269\|PubMed:18561205;Dbxref=dbSNP:rs55907433,PMID:12115348,PMI
P40692	632	663	656	656	Natural variant	ID=VAR_054537;Note=In HNPCC2%3B no effect on MLH1 splicing. F->S;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:18561205;Dbxref=dbSNP:rs267607876,PMID:18561205
P40692	632	663	657	657	Natural variant	ID=VAR_043433;Note=In HNPCC2%3B unknown pathological significance. Missing;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:16451135;Dbxref=PMID:16451135
P40692	632	663	659	659	Natural variant	ID=VAR_012929;Note=In HNPCC2. R->L;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:10713887,ECO:0000269\|PubMed:11427529;Dbxref=dbSNP:rs63749900,PMID:10713887,PMID:11427529
P40692	632	663	659	659	Natural variant	ID=VAR_004465;Note=In HNPCC2%3B interacts only very weakly with PMS2%3B abrogates interaction with EXO1%3B decreased mismatch repair activity%3B may lose nuclear localization. R->P;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,
P40692	632	663	659	659	Natural variant	ID=VAR_043434;Note=In HNPCC2%3B unknown pathological significance. R->Q;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:16083711,ECO:0000269\|PubMed:21120944;Dbxref=dbSNP:rs63749900,PMID:16083711,PMID:21120944
P40692	632	663	662	662	Natural variant	ID=VAR_012930;Note=In HNPCC2%3B unknown pathological significance. T->P;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:11726306,ECO:0000269\|PubMed:11754112;Dbxref=dbSNP:rs587778964,PMID:11726306,PMID:11754112
P40692	632	663	410	650	Region	Note=Interaction with EXO1;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:11427529,ECO:0000269\|PubMed:11429708,ECO:0000269\|PubMed:12414623,ECO:0000269\|PubMed:14676842,ECO:0000269\|PubMed:22753075;Dbxre

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3'-UTR located exon skipping events that lost miRNA binding sites in MLH1

3'-UTR exon skipping evnets lost miRNA binding.

Tissue type

ENST

Exon skip start

Exon skip end

microRNA

Binding site by TargetScan

Binding type by TargetScan

Bdinding site by miRanda

Score of miRanda

Energy by miRanda

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SNVs in the skipped exons for MLH1

- Differential PSIs between mutated versus non-mutated samples.

- Depth of Coverage in the skipped exon of the mutated samples.

- Sashimi plot in the skipped exon of the mutated samples.

- Non-synonymous mutations located in the skipped exons.

Cancer type

Sample

ESID

Skipped exon start

Skipped exon end

Mutation start

Mutation end

Mutation type

Reference seq

Mutation seq

AAchange

- Non-synonymous mutations located in the skipped exons in CCLE.

Sample

Skipped exon start

Skipped exon end

Mutation start

Mutation end

Mutation type

Reference seq

Mutation seq

AAchange

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AD stage-associated exon skippint events for MLH1

Associated exon skipping events with Braak staging or Clinical Dementia Rating (CDR).

AD stage info

Cohort

Tissue

SE id

Coefficient

P-value

Chromosome

Strand

E1 start

E1 end

Skipped start

Skipped end

E2 start

E2 end

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Splicing Quantitative Trait Loci (sQTL) in the exon skipping event for MLH1

sQTL information located at the skipped exons.

Tissue type

Exon skip ID

SNP id

Location

P-value

FDR

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Correlation with RNA binding proteins (RBPs) for MLH1

Correlated RBP and related information.

Tissue type	RBP name	Exon skip ID	Correlation coeifficient	P-value
CB	ELAVL1	exon_skip_93862	-4.589173e-01	3.098280e-09
CB	RBM6	exon_skip_93862	-4.246706e-01	5.493588e-08
CB	TRA2A	exon_skip_93862	-4.730335e-01	8.608631e-10
CB	SNRPA	exon_skip_93862	-4.991283e-01	6.882439e-11
CB	FUBP1	exon_skip_93862	-4.275175e-01	4.377546e-08
CB	HNRNPC	exon_skip_93862	-4.645081e-01	1.878699e-09
CB	PTBP1	exon_skip_93862	-4.963137e-01	9.132341e-11
CB	TARDBP	exon_skip_233995	-4.564064e-01	2.616336e-07
CB	RBM6	exon_skip_233995	-4.985982e-01	1.226783e-08
CB	TRA2A	exon_skip_233995	-4.717201e-01	9.034643e-08
CB	NUP42	exon_skip_233995	5.127428e-01	3.995114e-09
CB	TARDBP	exon_skip_168995	-4.830026e-01	2.934644e-10
CB	PABPN1	exon_skip_168995	-4.993289e-01	5.824677e-11
CB	CNOT4	exon_skip_168995	-4.452487e-01	9.052257e-09
CB	PCBP1	exon_skip_168995	-4.134511e-01	1.195960e-07
CB	TRA2A	exon_skip_168995	-4.391627e-01	1.514663e-08
CB	SNRPA	exon_skip_168995	-4.309376e-01	2.989212e-08
CB	HNRNPA2B1	exon_skip_168995	-4.115534e-01	1.383660e-07
CB	RBM45	exon_skip_168995	5.066931e-01	2.729972e-11
CB	HNRNPL	exon_skip_168995	-4.273058e-01	4.012768e-08
CB	HNRNPF	exon_skip_168995	-4.137904e-01	1.165074e-07
CB	RBM4	exon_skip_168995	-5.173035e-01	8.869907e-12
CB	FUBP1	exon_skip_154665	-4.090318e-01	8.648299e-08

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RelatedDrugs for MLH1

Approved drugs targeting this gene.
(DrugBank Version 5.1.0 2018-04-02)

UniProtAcc

DrugBank ID

Drug name

Drug activity

Drug type

Drug status

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RelatedDiseases for MLH1

Diseases associated with this gene.
(DisGeNet 4.0)

Gene

Disease ID

Disease name

# pubmeds

Source

	Gene summary
	Gene structures and expression levels
	Exon skipping events with PSIs in RPSMAP, MSBB, and Mayo
	Open reading frame (ORF) annotation in the exon skipping event
	Exon skipping events in the canonical protein sequence
	3'-UTR located exon skipping events lost miRNA binding sites
	SNVs in the skipped exons with depth of coverage
	AD stage-associated exon skipping events
	Splicing Quantitative Trait Loci (sQTLs) in the skipped exons
	Correlation with RNA binding proteins (RBPs)
	Related drugs with this gene
	Related diseases with this gene

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Gene summary for MLH1

Gene structures and expression levels for MLH1

Exon skipping events with PSIs in ROSMAP, MSBB, and Mayo for MLH1

Open reading frame (ORF) annotation in the exon skipping event for MLH1

Infer the effects of exon skipping event on protein functional features for MLH1

3'-UTR located exon skipping events that lost miRNA binding sites in MLH1

SNVs in the skipped exons for MLH1

AD stage-associated exon skippint events for MLH1

Splicing Quantitative Trait Loci (sQTL) in the exon skipping event for MLH1

Correlation with RNA binding proteins (RBPs) for MLH1

RelatedDrugs for MLH1

RelatedDiseases for MLH1