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Fusion gene ID: 7453 |
FusionGeneSummary for CLOCK_CLOCK |
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Fusion gene information | Fusion gene name: CLOCK_CLOCK | Fusion gene ID: 7453 | Hgene | Tgene | Gene symbol | CLOCK | CLOCK | Gene ID | 9575 | 9575 |
Gene name | clock circadian regulator | clock circadian regulator | |
Synonyms | KAT13D|bHLHe8 | KAT13D|bHLHe8 | |
Cytomap | 4q12 | 4q12 | |
Type of gene | protein-coding | protein-coding | |
Description | circadian locomoter output cycles protein kaputcircadian locomoter output cycles kaput proteinclass E basic helix-loop-helix protein 8clock homolog | circadian locomoter output cycles protein kaputcircadian locomoter output cycles kaput proteinclass E basic helix-loop-helix protein 8clock homolog | |
Modification date | 20180519 | 20180519 | |
UniProtAcc | O15516 | O15516 | |
Ensembl transtripts involved in fusion gene | ENST00000309964, ENST00000381322, ENST00000513440, ENST00000506923, | ENST00000309964, ENST00000381322, ENST00000513440, ENST00000506923, | |
Fusion gene scores | * DoF score | 6 X 8 X 5=240 | 3 X 4 X 1=12 |
# samples | 8 | 4 | |
** MAII score | log2(8/240*10)=-1.58496250072116 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(4/12*10)=1.73696559416621 effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs). DoF>8 and MAII>0 | |
Context | PubMed: CLOCK [Title/Abstract] AND CLOCK [Title/Abstract] AND fusion [Title/Abstract] | ||
Functional or gene categories assigned by FusionGDB annotation |
* DoF score (Degree of Frequency) = # partners X # break points X # cancer types ** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10) |
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Partner | Gene | GO ID | GO term | PubMed ID |
Hgene | CLOCK | GO:0006473 | protein acetylation | 28985504 |
Hgene | CLOCK | GO:0032922 | circadian regulation of gene expression | 24005054 |
Hgene | CLOCK | GO:0045893 | positive regulation of transcription, DNA-templated | 23785138 |
Hgene | CLOCK | GO:0051775 | response to redox state | 11441146 |
Hgene | CLOCK | GO:0071479 | cellular response to ionizing radiation | 21659603 |
Tgene | CLOCK | GO:0006473 | protein acetylation | 28985504 |
Tgene | CLOCK | GO:0032922 | circadian regulation of gene expression | 24005054 |
Tgene | CLOCK | GO:0045893 | positive regulation of transcription, DNA-templated | 23785138 |
Tgene | CLOCK | GO:0051775 | response to redox state | 11441146 |
Tgene | CLOCK | GO:0071479 | cellular response to ionizing radiation | 21659603 |
![]() (ChiTars (NAR, 2018), tumorfusions (NAR, 2018), Gao et al. (Cell, 2018)) * All genome coordinats were lifted-over on hg19. * Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser. |
Data type | Source | Cancer type | Sample | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand |
ChiTaRS3.1 | BE883242 | CLOCK | chr4 | 56299645 | + | CLOCK | chr4 | 56299610 | - | ||
ChiTaRS3.1 | AA484855 | CLOCK | chr4 | 56294355 | - | CLOCK | chr4 | 56294265 | + |
* LD: Li Ding group's fusion gene list RV: Roel Verhaak group's fusion gene list ChiTaRs fusion database |
![]() * Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser. |
ORF | Henst | Tenst | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand |
intron-3UTR | ENST00000309964 | ENST00000309964 | CLOCK | chr4 | 56299645 | + | CLOCK | chr4 | 56299610 | - |
intron-intron | ENST00000309964 | ENST00000381322 | CLOCK | chr4 | 56299645 | + | CLOCK | chr4 | 56299610 | - |
intron-intron | ENST00000309964 | ENST00000513440 | CLOCK | chr4 | 56299645 | + | CLOCK | chr4 | 56299610 | - |
intron-intron | ENST00000309964 | ENST00000506923 | CLOCK | chr4 | 56299645 | + | CLOCK | chr4 | 56299610 | - |
intron-3UTR | ENST00000381322 | ENST00000309964 | CLOCK | chr4 | 56299645 | + | CLOCK | chr4 | 56299610 | - |
intron-intron | ENST00000381322 | ENST00000381322 | CLOCK | chr4 | 56299645 | + | CLOCK | chr4 | 56299610 | - |
intron-intron | ENST00000381322 | ENST00000513440 | CLOCK | chr4 | 56299645 | + | CLOCK | chr4 | 56299610 | - |
intron-intron | ENST00000381322 | ENST00000506923 | CLOCK | chr4 | 56299645 | + | CLOCK | chr4 | 56299610 | - |
intron-3UTR | ENST00000513440 | ENST00000309964 | CLOCK | chr4 | 56299645 | + | CLOCK | chr4 | 56299610 | - |
intron-intron | ENST00000513440 | ENST00000381322 | CLOCK | chr4 | 56299645 | + | CLOCK | chr4 | 56299610 | - |
intron-intron | ENST00000513440 | ENST00000513440 | CLOCK | chr4 | 56299645 | + | CLOCK | chr4 | 56299610 | - |
intron-intron | ENST00000513440 | ENST00000506923 | CLOCK | chr4 | 56299645 | + | CLOCK | chr4 | 56299610 | - |
intron-3UTR | ENST00000506923 | ENST00000309964 | CLOCK | chr4 | 56299645 | + | CLOCK | chr4 | 56299610 | - |
intron-intron | ENST00000506923 | ENST00000381322 | CLOCK | chr4 | 56299645 | + | CLOCK | chr4 | 56299610 | - |
intron-intron | ENST00000506923 | ENST00000513440 | CLOCK | chr4 | 56299645 | + | CLOCK | chr4 | 56299610 | - |
intron-intron | ENST00000506923 | ENST00000506923 | CLOCK | chr4 | 56299645 | + | CLOCK | chr4 | 56299610 | - |
intron-3UTR | ENST00000309964 | ENST00000309964 | CLOCK | chr4 | 56294355 | - | CLOCK | chr4 | 56294265 | + |
intron-intron | ENST00000309964 | ENST00000381322 | CLOCK | chr4 | 56294355 | - | CLOCK | chr4 | 56294265 | + |
intron-intron | ENST00000309964 | ENST00000513440 | CLOCK | chr4 | 56294355 | - | CLOCK | chr4 | 56294265 | + |
intron-intron | ENST00000309964 | ENST00000506923 | CLOCK | chr4 | 56294355 | - | CLOCK | chr4 | 56294265 | + |
intron-3UTR | ENST00000381322 | ENST00000309964 | CLOCK | chr4 | 56294355 | - | CLOCK | chr4 | 56294265 | + |
intron-intron | ENST00000381322 | ENST00000381322 | CLOCK | chr4 | 56294355 | - | CLOCK | chr4 | 56294265 | + |
intron-intron | ENST00000381322 | ENST00000513440 | CLOCK | chr4 | 56294355 | - | CLOCK | chr4 | 56294265 | + |
intron-intron | ENST00000381322 | ENST00000506923 | CLOCK | chr4 | 56294355 | - | CLOCK | chr4 | 56294265 | + |
intron-3UTR | ENST00000513440 | ENST00000309964 | CLOCK | chr4 | 56294355 | - | CLOCK | chr4 | 56294265 | + |
intron-intron | ENST00000513440 | ENST00000381322 | CLOCK | chr4 | 56294355 | - | CLOCK | chr4 | 56294265 | + |
intron-intron | ENST00000513440 | ENST00000513440 | CLOCK | chr4 | 56294355 | - | CLOCK | chr4 | 56294265 | + |
intron-intron | ENST00000513440 | ENST00000506923 | CLOCK | chr4 | 56294355 | - | CLOCK | chr4 | 56294265 | + |
intron-3UTR | ENST00000506923 | ENST00000309964 | CLOCK | chr4 | 56294355 | - | CLOCK | chr4 | 56294265 | + |
intron-intron | ENST00000506923 | ENST00000381322 | CLOCK | chr4 | 56294355 | - | CLOCK | chr4 | 56294265 | + |
intron-intron | ENST00000506923 | ENST00000513440 | CLOCK | chr4 | 56294355 | - | CLOCK | chr4 | 56294265 | + |
intron-intron | ENST00000506923 | ENST00000506923 | CLOCK | chr4 | 56294355 | - | CLOCK | chr4 | 56294265 | + |
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FusionProtFeatures for CLOCK_CLOCK |
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Hgene | Tgene |
CLOCK | CLOCK |
Transcriptional activator which forms a core componentof the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes throughthe generation of approximately 24 hour circadian rhythms in geneexpression, which are translated into rhythms in metabolism andbehavior. It is derived from the Latin roots 'circa' (about) and'diem' (day) and acts as an important regulator of a wide array ofphysiological functions including metabolism, sleep, bodytemperature, blood pressure, endocrine, immune, cardiovascular,and renal function. Consists of two major components: the centralclock, residing in the suprachiasmatic nucleus (SCN) of the brain,and the peripheral clocks that are present in nearly every tissueand organ system. Both the central and peripheral clocks can bereset by environmental cues, also known as Zeitgebers (German for'timegivers'). The predominant Zeitgeber for the central clock islight, which is sensed by retina and signals directly to the SCN.The central clock entrains the peripheral clocks through neuronaland hormonal signals, body temperature and feeding-related cues,aligning all clocks with the external light/dark cycle. Circadianrhythms allow an organism to achieve temporal homeostasis with itsenvironment at the molecular level by regulating gene expressionto create a peak of protein expression once every 24 hours tocontrol when a particular physiological process is most activewith respect to the solar day. Transcription and translation ofcore clock components (CLOCK, NPAS2, ARNTL/BMAL1, ARNTL2/BMAL2,PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythmgeneration, whereas delays imposed by post-translationalmodifications (PTMs) are important for determining the period(tau) of the rhythms (tau refers to the period of a rhythm and isthe length, in time, of one complete cycle). A diurnal rhythm issynchronized with the day/night cycle, while the ultradian andinfradian rhythms have a period shorter and longer than 24 hours,respectively. Disruptions in the circadian rhythms contribute tothe pathology of cardiovascular diseases, cancer, metabolicsyndromes and aging. A transcription/translation feedback loop(TTFL) forms the core of the molecular circadian clock mechanism.Transcription factors, CLOCK or NPAS2 and ARNTL/BMAL1 orARNTL2/BMAL2, form the positive limb of the feedback loop, act inthe form of a heterodimer and activate the transcription of coreclock genes and clock-controlled genes (involved in key metabolicprocesses), harboring E-box elements (5'-CACGTG-3') within theirpromoters. The core clock genes: PER1/2/3 and CRY1/2 which aretranscriptional repressors form the negative limb of the feedbackloop and interact with the CLOCK|NPAS2-ARNTL/BMAL1|ARNTL2/BMAL2heterodimer inhibiting its activity and thereby negativelyregulating their own expression. This heterodimer also activatesnuclear receptors NR1D1/2 and RORA/B/G, which form a secondfeedback loop and which activate and repress ARNTL/BMAL1transcription, respectively. Regulates the circadian expression ofICAM1, VCAM1, CCL2, THPO and MPL and also acts as an enhancer ofthe transactivation potential of NF-kappaB. Plays an importantrole in the homeostatic regulation of sleep. The CLOCK-ARNTL/BMAL1heterodimer regulates the circadian expression of SERPINE1/PAI1,VWF, B3, CCRN4L/NOC, NAMPT, DBP, MYOD1, PPARGC1A, PPARGC1B, SIRT1,GYS2, F7, NGFR, GNRHR, BHLHE40/DEC1, ATF4, MTA1, KLF10 and alsogenes implicated in glucose and lipid metabolism. Promotesrhythmic chromatin opening, regulating the DNA accessibility ofother transcription factors. The CLOCK-ARNTL2/BMAL2 heterodimeractivates the transcription of SERPINE1/PAI1 and BHLHE40/DEC1. Thepreferred binding motif for the CLOCK-ARNTL/BMAL1 heterodimer is5'-CACGTGA-3', which contains a flanking Ala residue in additionto the canonical 6-nucleotide E-box sequence (PubMed:23229515).CLOCK specifically binds to the half-site 5'-CAC-3', while ARNTLbinds to the half-site 5'-GTGA-3' (PubMed:23229515). The CLOCK-ARNTL/BMAL1 heterodimer also recognizes the non-canonical E-boxmotifs 5'-AACGTGA-3' and 5'-CATGTGA-3' (PubMed:23229515). CLOCKhas an intrinsic acetyltransferase activity, which enablescircadian chromatin remodeling by acetylating histones andnonhistone proteins, including its own partner ARNTL/BMAL1.Represses glucocorticoid receptor NR3C1/GR-induced transcriptionalactivity by reducing the association of NR3C1/GR to glucocorticoidresponse elements (GREs) via the acetylation of multiple lysineresidues located in its hinge region (PubMed:21980503). Theacetyltransferase activity of CLOCK is as important as itstranscription activity in circadian control. Acetylates metabolicenzymes IMPDH2 and NDUFA9 in a circadian manner. Facilitated byBMAL1, rhythmically interacts and acetylates argininosuccinatesynthase 1 (ASS1) leading to enzymatic inhibition of ASS1 as wellas the circadian oscillation of arginine biosynthesis andsubsequent ureagenesis (PubMed:28985504).{ECO:0000269|PubMed:14645221, ECO:0000269|PubMed:18587630,ECO:0000269|PubMed:21659603, ECO:0000269|PubMed:21980503,ECO:0000269|PubMed:22284746, ECO:0000269|PubMed:23229515,ECO:0000269|PubMed:23785138, ECO:0000269|PubMed:24005054,ECO:0000269|PubMed:28985504}. | Transcriptional activator which forms a core componentof the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes throughthe generation of approximately 24 hour circadian rhythms in geneexpression, which are translated into rhythms in metabolism andbehavior. It is derived from the Latin roots 'circa' (about) and'diem' (day) and acts as an important regulator of a wide array ofphysiological functions including metabolism, sleep, bodytemperature, blood pressure, endocrine, immune, cardiovascular,and renal function. Consists of two major components: the centralclock, residing in the suprachiasmatic nucleus (SCN) of the brain,and the peripheral clocks that are present in nearly every tissueand organ system. Both the central and peripheral clocks can bereset by environmental cues, also known as Zeitgebers (German for'timegivers'). The predominant Zeitgeber for the central clock islight, which is sensed by retina and signals directly to the SCN.The central clock entrains the peripheral clocks through neuronaland hormonal signals, body temperature and feeding-related cues,aligning all clocks with the external light/dark cycle. Circadianrhythms allow an organism to achieve temporal homeostasis with itsenvironment at the molecular level by regulating gene expressionto create a peak of protein expression once every 24 hours tocontrol when a particular physiological process is most activewith respect to the solar day. Transcription and translation ofcore clock components (CLOCK, NPAS2, ARNTL/BMAL1, ARNTL2/BMAL2,PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythmgeneration, whereas delays imposed by post-translationalmodifications (PTMs) are important for determining the period(tau) of the rhythms (tau refers to the period of a rhythm and isthe length, in time, of one complete cycle). A diurnal rhythm issynchronized with the day/night cycle, while the ultradian andinfradian rhythms have a period shorter and longer than 24 hours,respectively. Disruptions in the circadian rhythms contribute tothe pathology of cardiovascular diseases, cancer, metabolicsyndromes and aging. A transcription/translation feedback loop(TTFL) forms the core of the molecular circadian clock mechanism.Transcription factors, CLOCK or NPAS2 and ARNTL/BMAL1 orARNTL2/BMAL2, form the positive limb of the feedback loop, act inthe form of a heterodimer and activate the transcription of coreclock genes and clock-controlled genes (involved in key metabolicprocesses), harboring E-box elements (5'-CACGTG-3') within theirpromoters. The core clock genes: PER1/2/3 and CRY1/2 which aretranscriptional repressors form the negative limb of the feedbackloop and interact with the CLOCK|NPAS2-ARNTL/BMAL1|ARNTL2/BMAL2heterodimer inhibiting its activity and thereby negativelyregulating their own expression. This heterodimer also activatesnuclear receptors NR1D1/2 and RORA/B/G, which form a secondfeedback loop and which activate and repress ARNTL/BMAL1transcription, respectively. Regulates the circadian expression ofICAM1, VCAM1, CCL2, THPO and MPL and also acts as an enhancer ofthe transactivation potential of NF-kappaB. Plays an importantrole in the homeostatic regulation of sleep. The CLOCK-ARNTL/BMAL1heterodimer regulates the circadian expression of SERPINE1/PAI1,VWF, B3, CCRN4L/NOC, NAMPT, DBP, MYOD1, PPARGC1A, PPARGC1B, SIRT1,GYS2, F7, NGFR, GNRHR, BHLHE40/DEC1, ATF4, MTA1, KLF10 and alsogenes implicated in glucose and lipid metabolism. Promotesrhythmic chromatin opening, regulating the DNA accessibility ofother transcription factors. The CLOCK-ARNTL2/BMAL2 heterodimeractivates the transcription of SERPINE1/PAI1 and BHLHE40/DEC1. Thepreferred binding motif for the CLOCK-ARNTL/BMAL1 heterodimer is5'-CACGTGA-3', which contains a flanking Ala residue in additionto the canonical 6-nucleotide E-box sequence (PubMed:23229515).CLOCK specifically binds to the half-site 5'-CAC-3', while ARNTLbinds to the half-site 5'-GTGA-3' (PubMed:23229515). The CLOCK-ARNTL/BMAL1 heterodimer also recognizes the non-canonical E-boxmotifs 5'-AACGTGA-3' and 5'-CATGTGA-3' (PubMed:23229515). CLOCKhas an intrinsic acetyltransferase activity, which enablescircadian chromatin remodeling by acetylating histones andnonhistone proteins, including its own partner ARNTL/BMAL1.Represses glucocorticoid receptor NR3C1/GR-induced transcriptionalactivity by reducing the association of NR3C1/GR to glucocorticoidresponse elements (GREs) via the acetylation of multiple lysineresidues located in its hinge region (PubMed:21980503). Theacetyltransferase activity of CLOCK is as important as itstranscription activity in circadian control. Acetylates metabolicenzymes IMPDH2 and NDUFA9 in a circadian manner. Facilitated byBMAL1, rhythmically interacts and acetylates argininosuccinatesynthase 1 (ASS1) leading to enzymatic inhibition of ASS1 as wellas the circadian oscillation of arginine biosynthesis andsubsequent ureagenesis (PubMed:28985504).{ECO:0000269|PubMed:14645221, ECO:0000269|PubMed:18587630,ECO:0000269|PubMed:21659603, ECO:0000269|PubMed:21980503,ECO:0000269|PubMed:22284746, ECO:0000269|PubMed:23229515,ECO:0000269|PubMed:23785138, ECO:0000269|PubMed:24005054,ECO:0000269|PubMed:28985504}. |
![]() * Minus value of BPloci means that the break pointn is located before the CDS. |
- In-frame and retained protein feature among the 13 regional features. |
Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
- In-frame and not-retained protein feature among the 13 regional features. |
Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
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FusionGeneSequence for CLOCK_CLOCK |
![]() (nt: nucleotides, aa: amino acids) |
* Fusion amino acid sequences. |
* Fusion transcript sequences (only coding sequence (CDS) region). |
* Fusion transcript sequences (Full-length transcript). |
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FusionGenePPI for CLOCK_CLOCK |
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Hgene | Hgene's interactors | Tgene | Tgene's interactors |
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Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Still interaction with |
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Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Interaction lost with |
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Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Interaction lost with |
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RelatedDrugs for CLOCK_CLOCK |
![]() (DrugBank Version 5.1.0 2018-04-02) |
Partner | Gene | UniProtAcc | DrugBank ID | Drug name | Drug activity | Drug type | Drug status |
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RelatedDiseases for CLOCK_CLOCK |
![]() (DisGeNet 4.0) |
Partner | Gene | Disease ID | Disease name | # pubmeds | Source |
Hgene | CLOCK | C0005586 | Bipolar Disorder | 5 | PSYGENET |
Hgene | CLOCK | C0011570 | Mental Depression | 5 | PSYGENET |
Hgene | CLOCK | C0011581 | Depressive disorder | 5 | PSYGENET |
Hgene | CLOCK | C0041696 | Unipolar Depression | 5 | PSYGENET |
Hgene | CLOCK | C0525045 | Mood Disorders | 5 | PSYGENET |
Hgene | CLOCK | C1269683 | Major Depressive Disorder | 5 | PSYGENET |
Hgene | CLOCK | C0085159 | Seasonal Affective Disorder | 3 | PSYGENET |
Hgene | CLOCK | C3496069 | cocaine use | 2 | PSYGENET |
Hgene | CLOCK | C0001957 | Alcohol Withdrawal Delirium | 1 | PSYGENET |
Hgene | CLOCK | C0001973 | Alcoholic Intoxication, Chronic | 1 | PSYGENET |
Hgene | CLOCK | C0036341 | Schizophrenia | 1 | PSYGENET |
Hgene | CLOCK | C0600427 | Cocaine Dependence | 1 | PSYGENET |
Tgene | CLOCK | C0005586 | Bipolar Disorder | 5 | PSYGENET |
Tgene | CLOCK | C0011570 | Mental Depression | 5 | PSYGENET |
Tgene | CLOCK | C0011581 | Depressive disorder | 5 | PSYGENET |
Tgene | CLOCK | C0041696 | Unipolar Depression | 5 | PSYGENET |
Tgene | CLOCK | C0525045 | Mood Disorders | 5 | PSYGENET |
Tgene | CLOCK | C1269683 | Major Depressive Disorder | 5 | PSYGENET |
Tgene | CLOCK | C0085159 | Seasonal Affective Disorder | 3 | PSYGENET |
Tgene | CLOCK | C3496069 | cocaine use | 2 | PSYGENET |
Tgene | CLOCK | C0001957 | Alcohol Withdrawal Delirium | 1 | PSYGENET |
Tgene | CLOCK | C0001973 | Alcoholic Intoxication, Chronic | 1 | PSYGENET |
Tgene | CLOCK | C0036341 | Schizophrenia | 1 | PSYGENET |
Tgene | CLOCK | C0600427 | Cocaine Dependence | 1 | PSYGENET |