CLOCK clock circadian regulator [Homo sapiens (human)] - Gene

Summary

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Official Symbol: CLOCKprovided by HGNC
Official Full Name: clock circadian regulatorprovided by HGNC
Primary source: HGNC:HGNC:2082
See related: Ensembl:ENSG00000134852 MIM:601851
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: KAT13D; bHLHe8
Summary: The protein encoded by this gene plays a central role in the regulation of circadian rhythms. The protein encodes a transcription factor of the basic helix-loop-helix (bHLH) family and contains DNA binding histone acetyltransferase activity. The encoded protein forms a heterodimer with ARNTL (BMAL1) that binds E-box enhancer elements upstream of Period (PER1, PER2, PER3) and Cryptochrome (CRY1, CRY2) genes and activates transcription of these genes. PER and CRY proteins heterodimerize and repress their own transcription by interacting in a feedback loop with CLOCK/ARNTL complexes. Polymorphisms in this gene may be associated with behavioral changes in certain populations and with obesity and metabolic syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]
Expression: Ubiquitous expression in testis (RPKM 7.8), thyroid (RPKM 6.2) and 24 other tissues See more
Orthologs: mouse all
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Annotation release	Status	Assembly	Chr	Location
109.20210514	current	GRCh38.p13 (GCF_000001405.39)	4	NC_000004.12 (55427903..55547138, complement)
105.20201022	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (56294070..56413076, complement)

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Clock gene polygenic risk score and seasonality in major depressive disorder and bipolar disorder.
Title: Clock gene polygenic risk score and seasonality in major depressive disorder and bipolar disorder.
For whom the circadian clock ticks? Investigation of PERIOD and CLOCK gene variants in bipolar disorder.
Title: For whom the circadian clock ticks? Investigation of PERIOD and CLOCK gene variants in bipolar disorder.
Rhythm and blues: Influence of CLOCK T3111C on peripheral electrophysiological indicators of negative affective processing.
Title: Rhythm and blues: Influence of CLOCK T3111C on peripheral electrophysiological indicators of negative affective processing.
Daily Changes in the Expression of Clock Genes in Sepsis and Their Relation with Sepsis Outcome and Urinary Excretion of 6-Sulfatoximelatonin.
Title: Daily Changes in the Expression of Clock Genes in Sepsis and Their Relation with Sepsis Outcome and Urinary Excretion of 6-Sulfatoximelatonin.
Circadian Regulator CLOCK Recruits Immune-Suppressive Microglia into the GBM Tumor Microenvironment.
Title: Circadian Regulator CLOCK Recruits Immune-Suppressive Microglia into the GBM Tumor Microenvironment.
Effects of Occupational Stress and Circadian CLOCK Gene Polymorphism on Sleep Quality of Oil Workers in Xinjiang, China.
Title: Effects of Occupational Stress and Circadian CLOCK Gene Polymorphism on Sleep Quality of Oil Workers in Xinjiang, China.
Elevated CLOCK and BMAL1 Contribute to the Impairment of Aerobic Glycolysis from Astrocytes in Alzheimer's Disease.
Title: Elevated CLOCK and BMAL1 Contribute to the Impairment of Aerobic Glycolysis from Astrocytes in Alzheimer's Disease.
Polymorphic Appetite Effects on Waist Circumference Depend on rs3749474 CLOCK Gene Variant.
Title: Polymorphic Appetite Effects on Waist Circumference Depend on rs3749474 CLOCK Gene Variant.
Clock knockdown attenuated reactive oxygen species-mediated senescence of chondrocytes through restoring autophagic flux.
Title: Clock knockdown attenuated reactive oxygen species-mediated senescence of chondrocytes through restoring autophagic flux.
Polymorphism of CLOCK Gene rs3749474 as a Modulator of the Circadian Evening Carbohydrate Intake Impact on Nutritional Status in an Adult Sample.
Title: Polymorphism of CLOCK Gene rs3749474 as a Modulator of the Circadian Evening Carbohydrate Intake Impact on Nutritional Status in an Adult Sample.

Submit: New GeneRIF Correction See all GeneRIFs (205)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Genome-wide association scan for five major dimensions of personality. GeneReviews: Not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of clock homolog (mouse, CLOCK) by siRNA inhibits the early stages of HIV-1 replication in 293T cells infected with VSV-G pseudotyped HIV-1	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

STS-R80639 (e-PCR)
- UniSTS:75273

SHGC-50712 (e-PCR)
- UniSTS:37

G54151 (e-PCR)
- UniSTS:109388

SHGC-59220 (e-PCR)
- UniSTS:25995

SHGC-67841 (e-PCR)
- UniSTS:49806

SHGC-106039 (e-PCR)
- UniSTS:169617

G16718 (e-PCR)
- UniSTS:75424

PMC55343P8 (e-PCR)
- UniSTS:273331

RH121148 (e-PCR)
- UniSTS:134143

Homology

Homologs of the CLOCK gene: The CLOCK gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 399 organisms have orthologs with human gene CLOCK
Orthologs

Clone Names

FLJ39000, FLJ42446, KIAA0334, DKFZp686I23208

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription activator activity, RNA polymerase II-specific	ISS Inferred from Sequence or Structural Similarity more info
enables DNA-binding transcription factor activity	ISS Inferred from Sequence or Structural Similarity more info
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IBA Inferred from Biological aspect of Ancestor more info	PubMed
enables DNA-binding transcription factor activity, RNA polymerase II-specific	ISA Inferred from Sequence Alignment more info
enables DNA-binding transcription factor activity, RNA polymerase II-specific	ISS Inferred from Sequence or Structural Similarity more info
enables E-box binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
enables E-box binding	IDA Inferred from Direct Assay more info	PubMed
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	ISS Inferred from Sequence or Structural Similarity more info
enables chromatin DNA binding	ISS Inferred from Sequence or Structural Similarity more info
enables histone acetyltransferase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein dimerization activity	IEA Inferred from Electronic Annotation more info
enables sequence-specific DNA binding	ISS Inferred from Sequence or Structural Similarity more info
enables sequence-specific double-stranded DNA binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA damage checkpoint signaling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to ionizing radiation	IDA Inferred from Direct Assay more info	PubMed
involved_in circadian regulation of gene expression	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in circadian regulation of gene expression	IDA Inferred from Direct Assay more info	PubMed
involved_in circadian regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in circadian regulation of gene expression	ISS Inferred from Sequence or Structural Similarity more info
involved_in circadian rhythm	TAS Traceable Author Statement more info	PubMed
involved_in histone acetylation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of glucocorticoid receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of transcription, DNA-templated	ISS Inferred from Sequence or Structural Similarity more info
involved_in photoperiodism	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of NF-kappaB transcription factor activity	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of inflammatory response	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within positive regulation of transcription by RNA polymerase II	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of transcription, DNA-templated	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of transcription, DNA-templated	ISS Inferred from Sequence or Structural Similarity more info
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein acetylation	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of circadian rhythm	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of hair cycle	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of insulin secretion	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in regulation of transcription, DNA-templated	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of type B pancreatic cell development	ISS Inferred from Sequence or Structural Similarity more info
involved_in response to redox state	IDA Inferred from Direct Assay more info	PubMed
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in spermatogenesis	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
part_of CLOCK-BMAL transcription complex	IBA Inferred from Biological aspect of Ancestor more info	PubMed
located_in chromatin	ISA Inferred from Sequence Alignment more info
located_in chromatoid body	ISS Inferred from Sequence or Structural Similarity more info
located_in chromosome	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
part_of transcription regulator complex	IPI Inferred from Physical Interaction more info	PubMed

General protein information

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Preferred Names: circadian locomoter output cycles protein kaput

Names: circadian locomoter output cycles kaput protein; class E basic helix-loop-helix protein 8; clock homolog

NP_001254772.1

EC 2.3.1.48

NP_004889.1

EC 2.3.1.48

XP_005265844.1

EC 2.3.1.48

XP_011532711.1

EC 2.3.1.48

XP_011532712.1

EC 2.3.1.48

XP_011532713.1

EC 2.3.1.48

XP_016864343.1

EC 2.3.1.48

XP_016864344.1

EC 2.3.1.48

XP_024310052.1

EC 2.3.1.48

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001267843.2 → NP_001254772.1 circadian locomoter output cycles protein kaput

See identical proteins and their annotated locations for NP_001254772.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript. Both variants 1 and 2 encode the same protein.

Source sequence(s)

AC069200, BC041878

Consensus CDS

CCDS3500.1

UniProtKB/Swiss-Prot

O15516

UniProtKB/TrEMBL

Q3ZCT4

Related

ENSP00000370723.1, ENST00000381322.5

Conserved Domains (4) summary

cd00083
Location:32 → 86

HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...

pfam00989
Location:109 → 175

PAS; PAS fold

pfam09606
Location:496 → 686

Med15; ARC105 or Med15 subunit of Mediator complex non-fungal

cl25986
Location:274 → 377

PAS_3; PAS fold
NM_004898.4 → NP_004889.1 circadian locomoter output cycles protein kaput

See identical proteins and their annotated locations for NP_004889.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Both variants 1 and 2 encode the same protein.

Source sequence(s)

AC069200, AK223549, DA658950

Consensus CDS

CCDS3500.1

UniProtKB/Swiss-Prot

O15516

UniProtKB/TrEMBL

Q53EU0

Related

ENSP00000426983.1, ENST00000513440.6

Conserved Domains (4) summary

cd00083
Location:32 → 86

HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...

pfam00989
Location:109 → 175

PAS; PAS fold

pfam09606
Location:496 → 686

Med15; ARC105 or Med15 subunit of Mediator complex non-fungal

cl25986
Location:274 → 377

PAS_3; PAS fold

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20210514

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000004.12 Reference GRCh38.p13 Primary Assembly

Range

55427903..55547138 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017008854.1 → XP_016864343.1 circadian locomoter output cycles protein kaput isoform X1

UniProtKB/Swiss-Prot

O15516

Conserved Domains (4) summary

cd00083
Location:32 → 86

HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...

pfam00989
Location:109 → 175

PAS; PAS fold

pfam09606
Location:496 → 686

Med15; ARC105 or Med15 subunit of Mediator complex non-fungal

cl25986
Location:274 → 377

PAS_3; PAS fold
XM_011534410.2 → XP_011532712.1 circadian locomoter output cycles protein kaput isoform X1

See identical proteins and their annotated locations for XP_011532712.1

UniProtKB/Swiss-Prot

O15516

Conserved Domains (4) summary

cd00083
Location:32 → 86

HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...

pfam00989
Location:109 → 175

PAS; PAS fold

pfam09606
Location:496 → 686

Med15; ARC105 or Med15 subunit of Mediator complex non-fungal

cl25986
Location:274 → 377

PAS_3; PAS fold
XM_005265787.2 → XP_005265844.1 circadian locomoter output cycles protein kaput isoform X1

See identical proteins and their annotated locations for XP_005265844.1

UniProtKB/Swiss-Prot

O15516

Conserved Domains (4) summary

cd00083
Location:32 → 86

HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...

pfam00989
Location:109 → 175

PAS; PAS fold

pfam09606
Location:496 → 686

Med15; ARC105 or Med15 subunit of Mediator complex non-fungal

cl25986
Location:274 → 377

PAS_3; PAS fold
XM_011534411.2 → XP_011532713.1 circadian locomoter output cycles protein kaput isoform X1

See identical proteins and their annotated locations for XP_011532713.1

UniProtKB/Swiss-Prot

O15516

Conserved Domains (4) summary

cd00083
Location:32 → 86

HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...

pfam00989
Location:109 → 175

PAS; PAS fold

pfam09606
Location:496 → 686

Med15; ARC105 or Med15 subunit of Mediator complex non-fungal

cl25986
Location:274 → 377

PAS_3; PAS fold
XM_024454284.1 → XP_024310052.1 circadian locomoter output cycles protein kaput isoform X1

Conserved Domains (4) summary

cd00083
Location:32 → 86

HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...

pfam00989
Location:109 → 175

PAS; PAS fold

pfam09606
Location:496 → 686

Med15; ARC105 or Med15 subunit of Mediator complex non-fungal

cl25986
Location:274 → 377

PAS_3; PAS fold
XM_011534409.2 → XP_011532711.1 circadian locomoter output cycles protein kaput isoform X1

See identical proteins and their annotated locations for XP_011532711.1

UniProtKB/Swiss-Prot

O15516

Conserved Domains (4) summary

cd00083
Location:32 → 86

HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...

pfam00989
Location:109 → 175

PAS; PAS fold

pfam09606
Location:496 → 686

Med15; ARC105 or Med15 subunit of Mediator complex non-fungal

cl25986
Location:274 → 377

PAS_3; PAS fold
XM_017008855.1 → XP_016864344.1 circadian locomoter output cycles protein kaput isoform X2