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; AllianceGenome:HGNC:2082
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
RS_2023_03	current	GRCh38.p14 (GCF_000001405.40)	4	NC_000004.12 (55427903..55546909, complement)
RS_2023_03	current	T2T-CHM13v2.0 (GCF_009914755.1)	4	NC_060928.1 (58916047..59035037, complement)
105.20220307	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?

Association of rotating night shift work, CLOCK, MTNR1A, MTNR1B genes polymorphisms and their interactions with type 2 diabetes among steelworkers: a case-control study.
Title: Association of rotating night shift work, CLOCK, MTNR1A, MTNR1B genes polymorphisms and their interactions with type 2 diabetes among steelworkers: a case-control study.
Nucleus-exported CLOCK acetylates PRPS to promote de novo nucleotide synthesis and liver tumour growth.
Title: Nucleus-exported CLOCK acetylates PRPS to promote de novo nucleotide synthesis and liver tumour growth.
Circadian regulator BMAL1::CLOCK promotes cell proliferation in hepatocellular carcinoma by controlling apoptosis and cell cycle.
Title: Circadian regulator BMAL1::CLOCK promotes cell proliferation in hepatocellular carcinoma by controlling apoptosis and cell cycle.
[Correlation analysis of clock genes and MEN2 medullary thyroid carcinoma].
Title: [Correlation analysis of clock genes and MEN2 medullary thyroid carcinoma].
Influence of CLOCK Gene Variants on Weight Response after Bariatric Surgery.
Title: Influence of CLOCK Gene Variants on Weight Response after Bariatric Surgery.
CLOCK Genetic Variations Are Associated With Age-Related Changes in Sleep Duration and Brain Volume.
Title: CLOCK Genetic Variations Are Associated With Age-Related Changes in Sleep Duration and Brain Volume.
Circadian protein CLOCK modulates regulatory B cell functions of nurses engaging day-night shift rotation.
Title: Circadian protein CLOCK modulates regulatory B cell functions of nurses engaging day-night shift rotation.
No significant association between SNPs in the CLOCK and ADH4 genes and susceptibility to cluster headaches: A systematic review and meta-analysis.
Title: No significant association between SNPs in the CLOCK and ADH4 genes and susceptibility to cluster headaches: A systematic review and meta-analysis.
Association between CLOCK 3111 T/C polymorphism with ghrelin, GLP-1, food timing, sleep and chronotype in overweight and obese Iranian adults.
Title: Association between CLOCK 3111 T/C polymorphism with ghrelin, GLP-1, food timing, sleep and chronotype in overweight and obese Iranian adults.
Circadian Regulator CLOCK Drives Immunosuppression in Glioblastoma.
Title: Circadian Regulator CLOCK Drives Immunosuppression in Glioblastoma.

Submit: New GeneRIF Correction See all GeneRIFs (223)

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

EBI GWAS Catalog

Description
Genome-wide association scan for five major dimensions of personality. EBI GWAS Catalog EBI GWAS CatalogPubMed

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

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	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 chromatin remodeling	IEA Inferred from Electronic Annotation more info
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 negative regulation of DNA-templated transcription	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of glucocorticoid receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in photoperiodism	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of DNA-templated transcription	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of NF-kappaB transcription factor activity	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of circadian rhythm	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of inflammatory response	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of transcription by RNA polymerase II	IEA Inferred from Electronic Annotation 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 DNA-templated transcription	ISS Inferred from Sequence or Structural Similarity more info
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 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
part_of CLOCK-BMAL transcription complex	IPI Inferred from Physical Interaction more info	PubMed
part_of 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

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_011532712.1

EC 2.3.1.48

XP_011532713.1

EC 2.3.1.48

XP_016864343.1

EC 2.3.1.48

XP_024310052.1

EC 2.3.1.48

XP_047272387.1

EC 2.3.1.48

XP_047272388.1

EC 2.3.1.48

XP_047272389.1

EC 2.3.1.48

XP_047272390.1

EC 2.3.1.48

XP_047272391.1

EC 2.3.1.48

XP_047272392.1

EC 2.3.1.48

XP_047272393.1

EC 2.3.1.48

XP_047272394.1

EC 2.3.1.48

XP_047272395.1

EC 2.3.1.48

XP_047272396.1

EC 2.3.1.48

XP_054207263.1

EC 2.3.1.48

XP_054207264.1

EC 2.3.1.48

XP_054207265.1

EC 2.3.1.48

XP_054207266.1

EC 2.3.1.48

XP_054207267.1

EC 2.3.1.48

XP_054207268.1

EC 2.3.1.48

XP_054207269.1

EC 2.3.1.48

XP_054207270.1

EC 2.3.1.48

XP_054207271.1

EC 2.3.1.48

XP_054207272.1

EC 2.3.1.48

XP_054207273.1

EC 2.3.1.48

XP_054207274.1

EC 2.3.1.48

XP_054207275.1

EC 2.3.1.48

XP_054207276.1

EC 2.3.1.48

XP_054207277.1

EC 2.3.1.48

XP_054207278.1

EC 2.3.1.48

NCBI Reference Sequences (RefSeq)

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NEW Try the new Transcript table

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, Q9UIT8

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, Q9UIT8

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: GCF_000001405.40-RS_2023_03

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000004.12 Reference GRCh38.p14 Primary Assembly

Range

55427903..55546909 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011534410.3 → 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, Q9UIT8

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_047416432.1 → XP_047272388.1 circadian locomoter output cycles protein kaput isoform X1

UniProtKB/Swiss-Prot

Q9UIT8
XM_047416436.1 → XP_047272392.1 circadian locomoter output cycles protein kaput isoform X1

UniProtKB/Swiss-Prot

Q9UIT8
XM_017008854.2 → XP_016864343.1 circadian locomoter output cycles protein kaput isoform X1

UniProtKB/Swiss-Prot

O15516, Q9UIT8

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_047416433.1 → XP_047272389.1 circadian locomoter output cycles protein kaput isoform X1

UniProtKB/Swiss-Prot

Q9UIT8
XM_011534411.3 → 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, Q9UIT8

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_047416439.1 → XP_047272395.1 circadian locomoter output cycles protein kaput isoform X1

UniProtKB/Swiss-Prot

Q9UIT8
XM_047416437.1 → XP_047272393.1 circadian locomoter output cycles protein kaput isoform X1

UniProtKB/Swiss-Prot

Q9UIT8
XM_005265787.3 → 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, Q9UIT8

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_047416431.1 → XP_047272387.1 circadian locomoter output cycles protein kaput isoform X1

UniProtKB/Swiss-Prot

Q9UIT8
XM_047416434.1 → XP_047272390.1 circadian locomoter output cycles protein kaput isoform X1

UniProtKB/Swiss-Prot

Q9UIT8
XM_047416435.1 → XP_047272391.1 circadian locomoter output cycles protein kaput isoform X1

UniProtKB/Swiss-Prot

Q9UIT8
XM_024454284.2 → XP_024310052.1 circadian locomoter output cycles protein kaput isoform X1

UniProtKB/Swiss-Prot

Q9UIT8

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_047416438.1 → XP_047272394.1 circadian locomoter output cycles protein kaput isoform X1

UniProtKB/Swiss-Prot

Q9UIT8
XM_047416440.1 → XP_047272396.1 circadian locomoter output cycles protein kaput isoform X1

UniProtKB/Swiss-Prot

Q9UIT8

Alternate T2T-CHM13v2.0

Genomic

NC_060928.1 Alternate T2T-CHM13v2.0

Range

58916047..59035037 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054351289.1 → XP_054207264.1 circadian locomoter output cycles protein kaput isoform X1

UniProtKB/Swiss-Prot

Q9UIT8
XM_054351290.1 → XP_054207265.1 circadian locomoter output cycles protein kaput isoform X1

UniProtKB/Swiss-Prot

Q9UIT8
XM_054351294.1 → XP_054207269.1 circadian locomoter output cycles protein kaput isoform X1

UniProtKB/Swiss-Prot

Q9UIT8
XM_054351288.1 → XP_054207263.1 circadian locomoter output cycles protein kaput isoform X1

UniProtKB/Swiss-Prot

Q9UIT8
XM_054351292.1 → XP_054207267.1 circadian locomoter output cycles protein kaput isoform X1

UniProtKB/Swiss-Prot

Q9UIT8
XM_054351297.1 → XP_054207272.1 circadian locomoter output cycles protein kaput isoform X1

UniProtKB/Swiss-Prot

Q9UIT8
XM_054351301.1 → XP_054207276.1 circadian locomoter output cycles protein kaput isoform X1

UniProtKB/Swiss-Prot

Q9UIT8
XM_054351296.1 → XP_054207271.1 circadian locomoter output cycles protein kaput isoform X1

UniProtKB/Swiss-Prot

Q9UIT8
XM_054351293.1 → XP_054207268.1 circadian locomoter output cycles protein kaput isoform X1

UniProtKB/Swiss-Prot

Q9UIT8
XM_054351295.1 → XP_054207270.1 circadian locomoter output cycles protein kaput isoform X1

UniProtKB/Swiss-Prot

Q9UIT8
XM_054351300.1 → XP_054207275.1 circadian locomoter output cycles protein kaput isoform X1

UniProtKB/Swiss-Prot

Q9UIT8
XM_054351302.1 → XP_054207277.1 circadian locomoter output cycles protein kaput isoform X1

UniProtKB/Swiss-Prot

Q9UIT8
XM_054351291.1 → XP_054207266.1 circadian locomoter output cycles protein kaput isoform X1

UniProtKB/Swiss-Prot

Q9UIT8
XM_054351299.1 → XP_054207274.1 circadian locomoter output cycles protein kaput isoform X1

UniProtKB/Swiss-Prot

Q9UIT8
XM_054351298.1 → XP_054207273.1 circadian locomoter output cycles protein kaput isoform X1

UniProtKB/Swiss-Prot

Q9UIT8
XM_054351303.1 → XP_054207278.1 circadian locomoter output cycles protein kaput isoform X1

UniProtKB/Swiss-Prot

Q9UIT8