CIPC

Summary

CIPC (CLOCK interacting pacemaker, HGNC:20365) is a protein-coding gene on chromosome 14q24.3, encoding CLOCK-interacting pacemaker (Q9C0C6). Transcriptional repressor which may act as a negative-feedback regulator of CLOCK-BMAL1 transcriptional activity in the circadian-clock mechanism.

Predicted to be involved in negative regulation of DNA-templated transcription and negative regulation of circadian rhythm. Located in cytosol; nucleolus; and nucleoplasm.

Source: NCBI Gene 85457 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 61 total
• MANE Select transcript: NM_033426

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20365
Approved symbol	CIPC
Name	CLOCK interacting pacemaker
Location	14q24.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000198894
Ensembl biotype	protein_coding
OMIM	616995
Entrez	85457

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 21 protein_coding, 1 retained_intron

ENST00000361786, ENST00000554447, ENST00000554658, ENST00000555200, ENST00000555437, ENST00000555611, ENST00000556863, ENST00000557115, ENST00000880022, ENST00000880023, ENST00000880024, ENST00000880025, ENST00000880026, ENST00000880027, ENST00000880028, ENST00000880029, ENST00000930386, ENST00000930387, ENST00000971302, ENST00000971303, ENST00000971304, ENST00000971305

RefSeq mRNA: 1 — MANE Select: NM_033426 NM_033426

CCDS: CCDS9855

Canonical transcript exons

ENST00000361786 — 4 exons

Exon	Start	End
ENSE00000911977	77109812	77109981
ENSE00000941065	77113425	77117287
ENSE00001240307	77098258	77098361
ENSE00003529256	77105657	77105844

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 97.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.0827 / max 215.5820, expressed in 1795 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
140756	16.9088	1794
140757	0.1739	70

Top tissues by expression

256 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.84	gold quality
quadriceps femoris	UBERON:0001377	97.73	gold quality
vastus lateralis	UBERON:0001379	97.69	gold quality
tibialis anterior	UBERON:0001385	97.33	gold quality
deltoid	UBERON:0001476	97.25	gold quality
skeletal muscle tissue	UBERON:0001134	97.19	gold quality
left ventricle myocardium	UBERON:0006566	96.61	gold quality
biceps brachii	UBERON:0001507	96.55	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.44	gold quality
gastrocnemius	UBERON:0001388	96.07	gold quality
muscle tissue	UBERON:0002385	96.05	gold quality
cardiac muscle of right atrium	UBERON:0003379	95.62	gold quality
muscle of leg	UBERON:0001383	95.54	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.36	gold quality
upper arm skin	UBERON:0004263	94.82	gold quality
bronchial epithelial cell	CL:0002328	94.71	gold quality
bronchus	UBERON:0002185	94.09	gold quality
lateral globus pallidus	UBERON:0002476	94.00	gold quality
corpus callosum	UBERON:0002336	93.84	gold quality
globus pallidus	UBERON:0001875	93.78	gold quality
inferior vagus X ganglion	UBERON:0005363	93.75	gold quality
medial globus pallidus	UBERON:0002477	93.74	gold quality
myocardium	UBERON:0002349	93.48	gold quality
lateral nuclear group of thalamus	UBERON:0002736	93.44	gold quality
subthalamic nucleus	UBERON:0001906	93.40	gold quality
mucosa of paranasal sinus	UBERON:0005030	93.38	gold quality
dorsal plus ventral thalamus	UBERON:0001897	93.35	gold quality
superior vestibular nucleus	UBERON:0007227	93.34	gold quality
cerebellum	UBERON:0002037	93.19	gold quality
cerebellar cortex	UBERON:0002129	93.09	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.74

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

171 targeting CIPC, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-590-3P	99.96	74.34	6478

Literature-anchored findings (GeneRIF, showing 1)

• Since CAD and Erk have significant roles in cell proliferation and cell cycle, CIPC may work as a cell cycle regulator by interacting with these binding proteins. (PMID:26657846)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cipca	ENSDARG00000075397
danio_rerio	cipcb	ENSDARG00000078095
mus_musculus	Cipc	ENSMUSG00000034157
rattus_norvegicus	Cipc	ENSRNOG00000011111

Protein

Protein identifiers

CLOCK-interacting pacemaker — Q9C0C6 (reviewed: Q9C0C6)

Alternative names: CLOCK-interacting circadian protein

All UniProt accessions (7): Q9C0C6, G3V310, G3V3Y7, G3V405, G3V4V0, G3V5J4, G3V5Y7

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional repressor which may act as a negative-feedback regulator of CLOCK-BMAL1 transcriptional activity in the circadian-clock mechanism. May stimulate BMAL1-dependent phosphorylation of CLOCK. However, the physiological relevance of these observations is unsure, since experiments in an animal model showed that CIPC is not critially required for basic circadian clock.

Subunit / interactions. Interacts with CLOCK. Forms a ternary complex with the CLOCK-BMAL1 heterodimer. Interacts with CAD and HSPA5.

Subcellular location. Nucleus. Cytoplasm. Cytosol.

RefSeq proteins (1): NP_219494* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR031602	CIPC	Family

Pfam: PF15800

UniProt features (13 total): region of interest 3, sequence variant 2, mutagenesis site 2, compositionally biased region 2, chain 1, coiled-coil region 1, short sequence motif 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9C0C6-F1	58.88	0.16

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 213

Mutagenesis-validated functional residues (2):

Position	Phenotype
186	loss of predominant localization in the nucleus; when associated with a-187. no effect on cad- and hspa5-binding; when a
187	loss of predominant localization in the nucleus; when associated with a-186. no effect on cad- and hspa5-binding; when a

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9931510	Phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) activates expression of core clock genes

MSigDB gene sets: 205 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GOBP_CIRCADIAN_RHYTHM, RNGTGGGC_UNKNOWN, GCM_PTPRD, GOLDRATH_IMMUNE_MEMORY, TGACCTY_ERR1_Q2, SRF_Q5_01, GOBP_REGULATION_OF_CIRCADIAN_RHYTHM, chr14q24, NF1_Q6_01, WCTCNATGGY_UNKNOWN, USF_01, GGCKCATGS_UNKNOWN, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN

GO Biological Process (3): negative regulation of circadian rhythm (GO:0042754), negative regulation of DNA-templated transcription (GO:0045892), rhythmic process (GO:0048511)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Circadian clock	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
nuclear lumen	2
circadian rhythm	1
regulation of circadian rhythm	1
negative regulation of biological process	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
biological_process	1
binding	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

420 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CIPC	CIART	Q8N365	530
CIPC	NR1D2	Q14995	505
CIPC	ITGB1BP1	O14713	439
CIPC	BMAL2	Q8WYA1	432
CIPC	PER3	P56645	411
CIPC	BMAL1	O00327	380
CIPC	MSRA	Q9UJ68	373
CIPC	PER2	O15055	370
CIPC	LIPC	P11150	370
CIPC	E2F6	O75461	347
CIPC	NPAS2	Q99743	345
CIPC	CEBPD	P49716	344
CIPC	RUNDC1	Q96C34	319
CIPC	RPS19	P39019	316
CIPC	CLOCK	O15516	307

IntAct

17 interactions, top by confidence:

A	B	Type	Score
COPS5	COPS2	psi-mi:“MI:0914”(association)	0.910
BMAL2	CLOCK	psi-mi:“MI:0914”(association)	0.670
CIPC	RABGEF1	psi-mi:“MI:0915”(physical association)	0.560
NCK2	CIPC	psi-mi:“MI:0915”(physical association)	0.560
CIPC	CLOCK	psi-mi:“MI:0914”(association)	0.530
COPS5	FBLL1	psi-mi:“MI:0914”(association)	0.350
COPS5	COPS2	psi-mi:“MI:0914”(association)	0.350
NPAS2	FHL2	psi-mi:“MI:0914”(association)	0.350
CIPC	BMAL1	psi-mi:“MI:0914”(association)	0.350
NCK2	CIPC	psi-mi:“MI:0915”(physical association)	0.000
VPS26C	CIPC	psi-mi:“MI:0915”(physical association)	0.000
APPL1	CIPC	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (27): CIPC (Two-hybrid), CIPC (Affinity Capture-RNA), CIPC (Affinity Capture-RNA), CLOCK (Two-hybrid), CSNK2B (Two-hybrid), DEC1 (Two-hybrid), RORC (Two-hybrid), CIPC (Affinity Capture-MS), ZMYM4 (Affinity Capture-MS), CLOCK (Affinity Capture-MS), CIPC (Affinity Capture-MS), CLOCK (Affinity Capture-MS), CIPC (Affinity Capture-MS), ZMYM4 (Affinity Capture-MS), CIPC (Two-hybrid)

ESM2 similar proteins: A0P8Z5, B0KYV5, B1WC58, B2RYR0, F1LR10, F6SNN2, O75128, O75410, P51826, P61590, P61591, P61592, P61593, P61594, Q3USH1, Q501R9, Q5IFK1, Q5PQK4, Q5R8C5, Q5SU73, Q5SWA1, Q5U5Q9, Q6NZF1, Q6P1D7, Q6P7W0, Q6PJW8, Q6Y685, Q6ZSG2, Q6ZVT6, Q7TT79, Q80XI1, Q80XJ2, Q80YR6, Q86T90, Q8BFU3, Q8C9B9, Q8IY92, Q8IYW5, Q8ND24, Q8NEM0

Diamond homologs: Q5R8C5, Q6NRH7, Q8R0W1, Q9C0C6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

61 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	59
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

709 predictions. Top by Δscore:

Variant	Effect	Δscore
14:77105656:GGGCA:G	acceptor_gain	1.0000
14:77105829:G:GT	donor_gain	1.0000
14:77098355:GCCC:G	donor_gain	0.9900
14:77105653:ATAG:A	acceptor_gain	0.9900
14:77105815:C:G	donor_gain	0.9900
14:77105842:CAG:C	donor_loss	0.9900
14:77105843:AG:A	donor_loss	0.9900
14:77105844:G:GC	donor_loss	0.9900
14:77105844:GG:G	donor_loss	0.9900
14:77105845:GTT:G	donor_loss	0.9900
14:77098360:AGGTG:A	donor_loss	0.9800
14:77098361:GGTGA:G	donor_loss	0.9800
14:77098362:GTG:G	donor_loss	0.9800
14:77098363:T:A	donor_loss	0.9800
14:77098363:T:G	donor_loss	0.9800
14:77098371:G:GT	donor_gain	0.9800
14:77098372:G:T	donor_gain	0.9800
14:77105652:CATA:C	acceptor_loss	0.9800
14:77105654:T:G	acceptor_gain	0.9800
14:77105655:A:AC	acceptor_loss	0.9800
14:77105655:A:AG	acceptor_gain	0.9800
14:77105656:G:GG	acceptor_gain	0.9800
14:77105846:T:G	donor_gain	0.9800
14:77106245:ATACT:A	donor_gain	0.9800
14:77105655:AG:A	acceptor_gain	0.9600
14:77105656:GG:G	acceptor_gain	0.9600
14:77105760:G:GG	donor_gain	0.9600
14:77109806:CACCA:C	acceptor_loss	0.9600
14:77109807:ACCAG:A	acceptor_loss	0.9600
14:77109808:CCA:C	acceptor_loss	0.9600

AlphaMissense

2595 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:77114089:T:C	L324P	0.999
14:77114104:T:C	L329S	0.999
14:77114176:T:C	L353P	0.999
14:77114068:T:C	F317S	0.998
14:77114089:T:A	L324Q	0.998
14:77114097:T:C	S327P	0.998
14:77114134:T:C	L339S	0.998
14:77105838:T:C	F44L	0.997
14:77105840:T:A	F44L	0.997
14:77105840:T:G	F44L	0.997
14:77114101:G:T	G328V	0.997
14:77114205:G:C	A363P	0.997
14:77114107:T:C	L330P	0.996
14:77114067:T:C	F317L	0.995
14:77114069:T:A	F317L	0.995
14:77114069:T:G	F317L	0.995
14:77114086:T:A	V323D	0.995
14:77114113:T:C	I332T	0.995
14:77114113:T:G	I332S	0.995
14:77114143:A:C	Q342P	0.995
14:77114167:T:C	L350P	0.995
14:77114074:A:T	N319I	0.994
14:77114080:T:C	L321P	0.994
14:77114089:T:G	L324R	0.993
14:77114104:T:G	L329W	0.992
14:77114242:T:C	L375P	0.992
14:77113609:C:A	A164D	0.991
14:77114068:T:G	F317C	0.991
14:77113585:T:C	I156T	0.990
14:77114064:C:A	R316S	0.990

dbSNP variants (sampled 300 via entrez): RS1000989953 (14:77106778 T>C), RS1001085758 (14:77115608 A>G), RS1001107859 (14:77101766 C>T), RS1001449272 (14:77116738 G>A), RS1001482400 (14:77104941 TCA>T), RS1001506814 (14:77102742 C>A,T), RS1001598403 (14:77105252 C>G), RS1002106176 (14:77096313 C>T), RS1002455357 (14:77115245 T>G), RS1002875250 (14:77115651 A>G), RS1002903036 (14:77100457 G>T), RS1003128160 (14:77103930 C>A,T), RS1003274383 (14:77103799 G>A), RS1003340082 (14:77097751 C>A,T), RS1003396959 (14:77104292 G>A)

Disease associations

OMIM: gene MIM:616995 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST008759_16	Intake of total sugars	4.000000e-06
GCST90011898_25	Alanine aminotransferase levels	3.000000e-08
GCST90011899_24	Aspartate aminotransferase levels	3.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0010158	sugar consumption measurement
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Smoke	increases expression, decreases expression, increases abundance	2
sodium arsenite	decreases expression	1
abrine	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases expression	1
Carbamazepine	affects expression	1
Cisplatin	increases expression	1
Doxorubicin	decreases expression	1
Hydrogen Peroxide	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Quercetin	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	affects expression	1
Cyclosporine	increases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.