CCK

Summary

CCK (cholecystokinin, HGNC:1569) is a protein-coding gene on chromosome 3p22.1, encoding Cholecystokinin (P06307). This peptide hormone induces gall bladder contraction and the release of pancreatic enzymes in the gut.

This gene encodes a member of the gastrin/cholecystokinin family of proteins. The encoded preproprotein is proteolytically processed to generate multiple protein products, including the peptide hormones cholecystokinin-8, -12, -33, and others. The encoded peptides have been shown to regulate gastric acid secretion and food intake. A sulfated form of cholecystokinin-8 may modulate neuronal activity in the brain. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 885 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 16 total
• Druggable target: yes
• MANE Select transcript: NM_000729

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1569
Approved symbol	CCK
Name	cholecystokinin
Location	3p22.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000187094
Ensembl biotype	protein_coding
OMIM	118440
Entrez	885

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 retained_intron

ENST00000334681, ENST00000396169, ENST00000434608, ENST00000484359, ENST00000869269, ENST00000951001, ENST00000951002

RefSeq mRNA: 2 — MANE Select: NM_000729 NM_000729, NM_001174138

CCDS: CCDS2696

Canonical transcript exons

ENST00000396169 — 5 exons

Exon	Start	End
ENSE00001331522	42263417	42263632
ENSE00001524127	42264697	42264907
ENSE00001524128	42265269	42265437
ENSE00001524129	42265684	42266185
ENSE00001715035	42257826	42258231

Expression profiles

Bgee: expression breadth ubiquitous, 171 present calls, max score 99.75.

FANTOM5 (CAGE): breadth broad, TPM avg 10.3414 / max 788.3912, expressed in 349 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
41781	10.2572	345
202735	0.0645	38
41782	0.0197	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
frontal pole	UBERON:0002795	99.75	gold quality
Brodmann (1909) area 10	UBERON:0013541	99.40	gold quality
prefrontal cortex	UBERON:0000451	99.03	gold quality
orbitofrontal cortex	UBERON:0004167	98.93	gold quality
middle temporal gyrus	UBERON:0002771	98.67	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	98.63	gold quality
cingulate cortex	UBERON:0003027	98.42	gold quality
anterior cingulate cortex	UBERON:0009835	98.40	gold quality
amygdala	UBERON:0001876	98.04	gold quality
frontal cortex	UBERON:0001870	97.92	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.65	gold quality
superior frontal gyrus	UBERON:0002661	97.26	gold quality
Brodmann (1909) area 46	UBERON:0006483	97.15	gold quality
right frontal lobe	UBERON:0002810	96.70	gold quality
neocortex	UBERON:0001950	96.69	gold quality
temporal lobe	UBERON:0001871	96.63	gold quality
cerebral cortex	UBERON:0000956	96.22	gold quality
parietal lobe	UBERON:0001872	95.93	gold quality
occipital lobe	UBERON:0002021	95.79	gold quality
primary visual cortex	UBERON:0002436	95.63	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.60	gold quality
postcentral gyrus	UBERON:0002581	95.55	gold quality
adult organism	UBERON:0007023	95.46	gold quality
Ammon’s horn	UBERON:0001954	94.95	gold quality
entorhinal cortex	UBERON:0002728	94.11	gold quality
duodenum	UBERON:0002114	93.75	gold quality
jejunal mucosa	UBERON:0000399	91.99	gold quality
CA1 field of hippocampus	UBERON:0003881	91.76	gold quality
endothelial cell	CL:0000115	91.29	gold quality
telencephalon	UBERON:0001893	91.26	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-HCAD-30	no	1424.11
E-ANND-3	no	0.96

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, CLOCK, CREB1, CREBBP, CREM, EN1, EWSR1, FLI1, FOS, FOSB, JUN, KMT2A, NFKB1, NFKB, PITX3, RELA, RREB1, SP1, SPI1, TFAP2A, USF1

miRNA regulators (miRDB)

35 targeting CCK, 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-574-5P	100.00	66.01	989
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-589-5P	98.72	66.96	927
HSA-MIR-34B-3P	98.70	67.40	1171
HSA-MIR-4710	98.61	65.96	1048
HSA-MIR-633	98.35	69.45	1167
HSA-MIR-4299	98.28	66.96	850
HSA-MIR-1245B-3P	98.01	68.91	1387
HSA-MIR-4638-3P	97.90	65.75	905
HSA-MIR-6791-3P	97.45	64.31	1123
HSA-MIR-6829-3P	97.45	64.31	1137

Literature-anchored findings (GeneRIF, showing 40)

• This article reviews the corpus of work supporting the role of CCK in anxiety and suggests three research approaches which can further enhance our understanding of the CCK-2 system in panic disorder. (PMID:11713976)
• This review describes the signaling pathways and transcription factors involved in neuronal CCK gene transcription. (PMID:11713982)
• Endoproteolytic processing events of heterologously expressed cholecystokinin are studied in Saccharomyces cerevisiae. (PMID:11713985)
• mapping of the CCK1R binding site by identifying residues that interact with the methionine and phenylalanine residues of the C-terminal moiety of CCK (PMID:11724786)
• Deteriorating gallbladder contractions, possibly induced by alterations in the CCK-AR gene, as well as CCK-AR gene polymorphism, promoted gallstone formation. (PMID:12572876)
• Results suggest that the L-(-188G) haplotype may act as a protective factor against panic by reducing the expression of anxiogenic cholecystokinin (CCK). (PMID:12627463)
• in Chinese, visual hallucinations in Parkinson’s disease are associated with cholecystokinin -45C>T polymorphism, and this association was still observed in the presence of the cholecystokinin-A receptor TC/CC genotype (PMID:12777967)
• reduced basal hunger, rather than increased meal-induced satiety, contributes to the anorexia of aging and that changes in cholecystokinin are unlikely to be responsible (PMID:12915664)
• CCK’s suppression of food intake is enhanced when the stomach is distended. (PMID:12920059)
• Ingestion of a CCK-releasing fatty acid reduces the tolerated volume of liquid delivered into the stomach, primarily via a CCK(1) receptor-mediated delay in gastric emptying. (PMID:14764444)
• Review summarizes the physiological role of CCK not only in the stimulation of pancreatic and biliary secretions but also in the regulation of gastrointestinal motility. (PMID:15100163)
• Study based on a small, well-characterized matched case-control group of patients with Parkinson disease (PD) suggests that the cholecystokinin system may influence the development of hallucinations in PD subjects. (PMID:15313848)
• Ewing sarcomas synthesize and secrete proCCK that can be identified in plasma as circulating tumor marker. (PMID:15328192)
• CCK regulates pancreatic enzyme secretion and growth, intestinal motility, satiety signalling and the inhibition of gastric acid secretion–REVIEW (PMID:15533776)
• conclude that women with polycystic ovary syndrome (PCOS) have reduced postprandial cholecystokinin(CCK) secretion and deranged appetite regulation associated with increased levels of testosterone (PMID:15624269)
• Gastrin and CCK exert a trophic action on some of the biliary tract cancers. (PMID:15682471)
• The mu-opiate receptor agonist loperamide inhibits bethanechol-induced gallbladder contraction, which is not mediated by inhibition of CCK release. (PMID:16185316)
• Allelic variants are specifically associated with distinctly different eating patterns, namely extreme snacking behavior or excessive portion size. (PMID:17192493)
• Differences in summer and winter and in diurnal blood levels correlated with external temperature. (PMID:17208296)
• Acid stable fat emulsions increased postprandial CCK levels. (PMID:17332474)
• results fail to support prior evidence of an association of the CCK C-45T polymorphism with the ability to quit smoking (PMID:17365745)
• CCK acts as an autocrine growth factor stimulating the proliferation of Ewing cells. suggesting that therapies targeting CCK could be promising in the treatment of Ewing tumors. (PMID:17438102)
• Cholecystokinin concentrations followed a pattern that predicted the subjective satiety in women, but not in men. (PMID:17964616)
• No change in absorption spectrum was observed on addition of ferric ions indicating that the binding of procholecystokinin(57-95) to ferric ions was very weak. (PMID:18066654)
• In critical illness plasma cholecystokinin levels correlate moderately with impaired gastric emptying, in a complex interaction with peptide YY. (PMID:18154642)
• There are notable differences in leptin, serum lipid, and CCK between patients with gallstone and those with hepatolithiasis (PMID:18234641)
• There is regional variation in CCK in the upper small intestine. (PMID:18396340)
• CCK peptide is abundant in human gliomas and acts to stimulate cell growth (PMID:18423848)
• CCK elicits cytosolic Ca(2+) signaling, activates mitochondrial function, and stimulates enzyme secretion in isolated human pancreatic acinar cells. Conclude that CCK acts directly on acinar cells in the human pancreas. (PMID:18555802)
• Advanced age determines a reduced CCK postprandial response. (PMID:19339394)
• Our data indicate that CCK, acting via CCK(B) receptors, produces a long-lasting excitation of layer 6b neocortical neurons, and this action may play a critical role in modulation of corticothalamic circuit activity. (PMID:19497313)
• Three classes of depolarization-induced suppression of inhibition-expressing, cholecystokinin (CCK)-containing, transgenic hippocampal interneurons show highly asynchronous release in response to trains of action potentials. (PMID:19741117)
• Our data suggest that the 779 T carriers of CCK-1 intron 1 is associated with an increased risk of PDS in Japanese male subjects. (PMID:19760980)
• Cefaclor, when given before a meal in the form of a capsule, does not stimulate CCK release or slow gastric emptying in healthy humans. (PMID:19914303)
• results suggest that the CCK system may play a role in the pathogenesis of panic disorder, with susceptibility alleles both protecting and contributing to the disease (PMID:20023595)
• REVIEW: role in thermoregulation and other aspects of energetics (PMID:20036221)
• Study compared CCK-like immunoreactivity (CCK-LI) in plasma from 25 subjects in the late luteal phase (LLP) and the follicular phase (FP) and found that there was no difference during the menstrual cycle (PMID:20457200)
• Cholecystokinin gene polymorphisms are not associated with antipsychotic induced weight gain in schizophrenia patients. (PMID:20732371)
• These results point to a potential route of action by which components of Hoodia might influence appetite control; the natural taste receptor antagonist was identified for further studies as an appetite suppressant. (PMID:20930049)
• CCK modulates intrinsic neuronal excitability and synaptic transmission in a surprisingly cell-type specific manner, acting as a key molecular switch to regulate the functional output of neuronal circuits. (PMID:21154912)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccka	ENSDARG00000070810
		ENSDARG00000100052
mus_musculus	Cck	ENSMUSG00000032532
rattus_norvegicus	Cck	ENSRNOG00000019321

Protein

Protein identifiers

Cholecystokinin — P06307 (reviewed: P06307)

All UniProt accessions (2): P06307, Q6FG82

UniProt curated annotations — full annotation on UniProt →

Function. This peptide hormone induces gall bladder contraction and the release of pancreatic enzymes in the gut. Its function in the brain is not clear. Binding to CCK-A receptors stimulates amylase release from the pancreas, binding to CCK-B receptors stimulates gastric acid secretion.

Subunit / interactions. Binds to CCK-A receptors in the pancreas and CCK-B receptors in the brain.

Subcellular location. Secreted.

Tissue specificity. Detected in cerebrospinal fluid and urine (at protein level).

Post-translational modifications. The precursor is cleaved by proteases to produce a number of active cholecystokinins. The precursor is cleaved by ACE, which removes the Gly-Arg-Arg peptide at the C-terminus, leading to mature hormone.

Similarity. Belongs to the gastrin/cholecystokinin family.

RefSeq proteins (2): NP_000720, NP_001167609 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001651	Gastrin/CCK	Domain
IPR013152	Gastrin/cholecystokinin_CS	Conserved_site
IPR015499	CCK-like	Family

Pfam: PF00918

UniProt features (23 total): peptide 10, modified residue 4, propeptide 2, sequence variant 2, signal peptide 1, chain 1, region of interest 1, glycosylation site 1, mutagenesis site 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
7MBX	ELECTRON MICROSCOPY	1.95
7MBY	ELECTRON MICROSCOPY	2.44
9BKK	ELECTRON MICROSCOPY	2.51
9BKJ	ELECTRON MICROSCOPY	2.59
7EZM	ELECTRON MICROSCOPY	2.9
7EZK	ELECTRON MICROSCOPY	3.1
8IA7	ELECTRON MICROSCOPY	3.1
7EZH	ELECTRON MICROSCOPY	3.2
7XOU	ELECTRON MICROSCOPY	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P06307-F1	64.72	0.05

Antibody-complex structures (SAbDab): 5 — 7EZH, 7EZM, 7MBX, 7XOU, 8IA7

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 (4): 97, 103, 111, 113

Glycosylation sites (1): 31

Mutagenesis-validated functional residues (1):

Position	Phenotype
97	reduces the quantity of secreted cck8 by 50%.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-416476	G alpha (q) signalling events
R-HSA-162582	Signal Transduction
R-HSA-372790	Signaling by GPCR
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-388396	GPCR downstream signalling
R-HSA-500792	GPCR ligand binding

MSigDB gene sets: 134 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, GOBP_DIGESTION, MODY_HIPPOCAMPUS_POSTNATAL, GOBP_BEHAVIOR, STAEGE_EWING_FAMILY_TUMOR, ENK_UV_RESPONSE_KERATINOCYTE_UP, MODULE_64, GOBP_NEUROGENESIS, BROWNE_HCMV_INFECTION_12HR_UP, MODULE_66, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, GOBP_EATING_BEHAVIOR, MODULE_379, chr3p22, GOBP_NEURON_MIGRATION

GO Biological Process (6): neuron migration (GO:0001764), signal transduction (GO:0007165), axonogenesis (GO:0007409), digestion (GO:0007586), cholecystokinin signaling pathway (GO:0038188), eating behavior (GO:0042755)

GO Molecular Function (5): hormone activity (GO:0005179), neuropeptide hormone activity (GO:0005184), peptide hormone receptor binding (GO:0051428), protein binding (GO:0005515), receptor ligand activity (GO:0048018)

GO Cellular Component (3): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), axon (GO:0030424)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Signaling by GPCR	2
Class A/1 (Rhodopsin-like receptors)	1
GPCR downstream signalling	1
Signal Transduction	1
GPCR ligand binding	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell migration	1
generation of neurons	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
axon development	1
multicellular organismal process	1
G protein-coupled receptor signaling pathway	1
feeding behavior	1
receptor ligand activity	1
hormone activity	1
neuropeptide activity	1
hormone receptor binding	1
binding	1
signaling receptor binding	1
signal transduction	1
signaling receptor activator activity	1
cellular anatomical structure	1
neuron projection	1

Protein interactions and networks

STRING

5154 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCK	CCKAR	P32238	999
CCK	CCKBR	P32239	999
CCK	CCL28	Q9NRJ3	995
CCK	GAST	P01350	989
CCK	GRP	P07491	952
CCK	GHRL	Q9UBU3	933
CCK	PTK7	Q13308	923
CCK	SST	P01166	922
CCK	NPY	P01303	907
CCK	PYY	P10082	903
CCK	ANXA5	P08758	891
CCK	NTS	P30990	886
CCK	LEP	P41159	883
CCK	GAPDH	P00354	882
CCK	SCT	P09683	876

IntAct

176 interactions, top by confidence:

A	B	Type	Score
CCK	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
CCK	FYN	psi-mi:“MI:0915”(physical association)	0.560
GABPB1	CCK	psi-mi:“MI:0915”(physical association)	0.560
CCK	HCCS	psi-mi:“MI:0915”(physical association)	0.560
HELLS	CCK	psi-mi:“MI:0915”(physical association)	0.560
CCK	CITED1	psi-mi:“MI:0915”(physical association)	0.560
CCK	MYC	psi-mi:“MI:0915”(physical association)	0.560
CCK	NFYB	psi-mi:“MI:0915”(physical association)	0.560
PPARA	CCK	psi-mi:“MI:0915”(physical association)	0.560
CCK	PPBP	psi-mi:“MI:0915”(physical association)	0.560
PTPN4	CCK	psi-mi:“MI:0915”(physical association)	0.560
CCK	PRPH2	psi-mi:“MI:0915”(physical association)	0.560
CCK	RELA	psi-mi:“MI:0915”(physical association)	0.560
CCK	RGR	psi-mi:“MI:0915”(physical association)	0.560
RHEB	CCK	psi-mi:“MI:0915”(physical association)	0.560
RPS4X	CCK	psi-mi:“MI:0915”(physical association)	0.560
UBE2G1	CCK	psi-mi:“MI:0915”(physical association)	0.560
CCK	EPM2A	psi-mi:“MI:0915”(physical association)	0.560
CCK	SYMPK	psi-mi:“MI:0915”(physical association)	0.560
CCK	CBX4	psi-mi:“MI:0915”(physical association)	0.560
CCK	ATG12	psi-mi:“MI:0915”(physical association)	0.560
CCK	H2AP	psi-mi:“MI:0915”(physical association)	0.560
CCK	JPT1	psi-mi:“MI:0915”(physical association)	0.560
CCK	ARL6IP4	psi-mi:“MI:0915”(physical association)	0.560
CCK	VPS54	psi-mi:“MI:0915”(physical association)	0.560
CIAO2B	CCK	psi-mi:“MI:0915”(physical association)	0.560
CCK	NUP54	psi-mi:“MI:0915”(physical association)	0.560
BRWD1	CCK	psi-mi:“MI:0915”(physical association)	0.560
CCK	ADAMTSL4	psi-mi:“MI:0915”(physical association)	0.560
CCK	WBP1L	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (6): CCKBR (Reconstituted Complex), CCKBR (Reconstituted Complex), CCKBR (Reconstituted Complex), UBQLN2 (Two-hybrid), CCK (Protein-peptide), TRIM68 (Affinity Capture-MS)

ESM2 similar proteins: B2RZ42, D4A6L0, E1BBQ2, J3QPP8, O02695, O62827, P01346, P01356, P06307, P06881, P09535, P12755, P12843, P15473, P16611, P17936, P20959, P22444, P22692, P24854, P47878, P49002, P49192, P49705, P53366, P55107, P55108, P56388, P80560, P97737, Q05716, Q08DX6, Q16568, Q26492, Q4RU86, Q58CS8, Q5T848, Q63475, Q68RJ9, Q6DVA0

Diamond homologs: E2E4E4, O57312, O93464, P01355, P01356, P06307, P09240, P23362, P41520, P50144, P50145, P80344, P80345, Q8JHB9, Q9PU29, Q9PU41, Q9TS44, P80111, P16240, P05226, C0HKM5, C0HKM6, C0HKM7, C0HKM8, C0HKM9, C0HKN1, C0HKN2, P01357, P05222, P05223, P05224, P05225, P07198, P11006, P13684, O02686, P01353, P04563, P09859, P55885

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
CCK	up-regulates	CCKBR	binding
CCK	up-regulates	CCKAR	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	13
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

201 predictions. Top by Δscore:

Variant	Effect	Δscore
3:42263411:TCTTA:T	donor_loss	1.0000
3:42263412:CTTA:C	donor_loss	1.0000
3:42263413:TTACC:T	donor_loss	1.0000
3:42263414:TA:T	donor_loss	1.0000
3:42263415:A:AC	donor_gain	1.0000
3:42263415:ACCTT:A	donor_loss	1.0000
3:42263416:C:CC	donor_gain	1.0000
3:42263416:C:CT	donor_loss	1.0000
3:42263416:CCTTT:C	donor_gain	1.0000
3:42263630:TGG:T	acceptor_gain	1.0000
3:42263633:C:CC	acceptor_gain	1.0000
3:42264693:CTACC:C	donor_loss	1.0000
3:42264694:TACCT:T	donor_loss	1.0000
3:42264696:C:CG	donor_loss	1.0000
3:42258242:C:CT	acceptor_gain	0.9900
3:42258243:A:T	acceptor_gain	0.9900
3:42263415:AC:A	donor_gain	0.9900
3:42263416:CC:C	donor_gain	0.9900
3:42263416:CCT:C	donor_gain	0.9900
3:42263628:CATGG:C	acceptor_gain	0.9900
3:42263629:ATGG:A	acceptor_gain	0.9900
3:42263631:GG:G	acceptor_gain	0.9900
3:42263631:GGC:G	acceptor_loss	0.9900
3:42263632:GC:G	acceptor_loss	0.9900
3:42264695:A:AC	donor_gain	0.9900
3:42264696:C:CC	donor_gain	0.9900
3:42258232:C:CC	acceptor_gain	0.9800
3:42263635:G:C	acceptor_gain	0.9800
3:42263635:G:GC	acceptor_gain	0.9800
3:42263639:C:CT	acceptor_gain	0.9800

AlphaMissense

732 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:42258137:A:C	F103L	0.999
3:42258137:A:T	F103L	0.999
3:42258139:A:G	F103L	0.999
3:42258146:C:A	W100C	0.999
3:42258146:C:G	W100C	0.999
3:42258148:A:G	W100R	0.999
3:42258148:A:T	W100R	0.999
3:42258138:A:C	F103C	0.997
3:42258141:T:A	D102V	0.995
3:42258151:C:G	G99R	0.995
3:42258130:G:T	R106S	0.994
3:42258135:C:T	G104D	0.994
3:42258138:A:G	F103S	0.994
3:42258133:G:T	R105S	0.993
3:42258135:C:A	G104V	0.993
3:42258140:A:C	D102E	0.993
3:42258140:A:T	D102E	0.993
3:42258141:T:G	D102A	0.993
3:42258142:C:G	D102H	0.993
3:42258144:A:G	M101T	0.993
3:42258141:T:C	D102G	0.992
3:42258147:C:G	W100S	0.992
3:42258159:T:A	D96V	0.992
3:42258125:A:C	S107R	0.991
3:42258125:A:T	S107R	0.991
3:42258127:T:G	S107R	0.991
3:42258136:C:G	G104R	0.991
3:42258151:C:A	G99C	0.991
3:42258139:A:T	F103I	0.990
3:42258143:C:A	M101I	0.990

dbSNP variants (sampled 300 via entrez): RS1000102664 (3:42260943 T>C), RS1000116399 (3:42266000 C>T), RS1000275274 (3:42265792 A>C), RS1000537790 (3:42258847 T>C), RS1000549312 (3:42259075 C>T), RS1000640715 (3:42263556 G>A,C), RS1001150915 (3:42257330 A>G), RS1001347581 (3:42266470 G>A), RS1001522326 (3:42260096 A>G), RS1001639344 (3:42257961 C>A), RS1001763525 (3:42257697 C>T), RS1002545314 (3:42261640 A>G), RS1002619912 (3:42263408 C>T), RS1002721027 (3:42262566 C>T), RS1002944239 (3:42261356 G>A)

Disease associations

OMIM: gene MIM:118440 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST001416_8	Body mass index (SNP x SNP interaction)	2.000000e-07
GCST002301_2	Body mass index	1.000000e-06
GCST003542_74	Night sleep phenotypes	2.000000e-06
GCST004557_179	Body mass index	4.000000e-08
GCST004557_42	Body mass index	1.000000e-08
GCST004558_127	Body mass index (joint analysis main effects and physical activity interaction)	6.000000e-07
GCST004558_226	Body mass index (joint analysis main effects and physical activity interaction)	3.000000e-07
GCST004904_156	Body mass index	3.000000e-11
GCST004904_227	Body mass index	4.000000e-09
GCST010988_136	Adult body size	4.000000e-13
GCST010989_216	Body size at age 10	6.000000e-13

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0007827	nighttime rest measurement
EFO:0008002	physical activity measurement
EFO:0009819	comparative body size at age 10, self-reported

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1649050 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

50 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Octreotide	decreases response to substance, decreases secretion	5
Valproic Acid	increases expression, increases methylation, affects cotreatment, decreases expression, affects expression	4
Olive Oil	increases expression, increases secretion, decreases reaction	3
Orlistat	decreases reaction, increases secretion, decreases abundance, decreases secretion	3
Aflatoxin B1	increases expression	3
osteum	increases secretion	2
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	2
Cadmium Chloride	decreases expression, increases abundance	2
methylmercuric chloride	increases expression	1
propionaldehyde	increases expression	1
methylselenic acid	increases expression	1
trichostatin A	decreases expression	1
arsenite	increases methylation	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
zinc chromate	increases expression, increases abundance	1
S-(1,2-dichlorovinyl)cysteine	decreases expression	1
pentanal	increases expression	1
dinophysistoxin 1	increases expression	1
chromium hexavalent ion	increases abundance, increases expression	1
cylindrospermopsin	increases expression	1
CGP 52608	increases reaction, affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, increases expression, affects cotreatment	1
quinocetone	increases expression	1
ormosil	affects binding, increases expression	1
dorsomorphin	affects cotreatment, decreases expression, increases expression	1
Decitabine	increases expression	1
Vorinostat	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Aldehydes	increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1646091	Binding	Inhibition of human Cck	Click chemistry inspired one-pot synthesis of 1,4-disubstituted 1,2,3-triazoles and their Src kinase inhibitory activity. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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