CCK

protein-coding

cholecystokinin, the group of Neuropeptides

Gene summary

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. [provided by RefSeq, Nov 2015]

MANE transcript

NM_000729.6

Inheritance

—

ClinVar variants

U:11B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.31

Max pathogenic AF

—

Genomic locus

chr3:42,257,825-42,266,185

External References & Databases

Ensembl (ENSG00000187094)

Transcript & Mutation Effects

hg38 • Region Span ~8.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CCK variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 13

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000729.6. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			11 clinvar	2 clinvar		13
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	11	2	0	13

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000729.6	RefSeq	NP_000720.1	2	MANE Select
ENST00000396169.7	Ensembl	ENSP00000379472.2	2	MANE Select
NM_001174138.3	RefSeq	NP_001167609.1	2	Standard
ENST00000334681.10	Ensembl	ENSP00000335657.5	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Gastric acid production
Cell-type Dependent Selectivity of CCK2R Signaling
Signaling by GPCR
Signal Transduction
GPCR signaling-G alpha q

Biological Process

neuron migration
release of cytochrome c from mitochondria
activation of cysteine-type endopeptidase activity involved in apoptotic process
signal transduction
G protein-coupled receptor signaling pathway

Molecular Function

hormone activity
neuropeptide hormone activity
peptide hormone receptor binding

Cellular Component

extracellular region
extracellular space
axon
dendrite
axon initial segment

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000396169
Coding exons: 2
Length: 8383
Individuals with no LoFs: 125735
Homozygous LoFs: 0
Heterozygous LoFs: 11
Defined: 125746
p: 0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.653	58	73.8	0.786	0.00000400	724
Missense (PolyPhen)		24	29.3	0.8191		269
Synonymous	-0.00655	33	33.0	1.00	0.00000161	250
Loss of Function	-0.606	6	4.60	1.30	3.00e-7	36

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0.000098	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: 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.;

Recessive Scores

pRec: 0.194

Intolerance Scores

LoFtool: 0.545
RVIS EVS: -0.03
RVIS percentile EVS: 51.04

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium