GRPR

protein-coding

gastrin releasing peptide receptor, the group of Bombesin receptors

Gene summary

Gastrin-releasing peptide (GRP) regulates numerous functions of the gastrointestinal and central nervous systems, including release of gastrointestinal hormones, smooth muscle cell contraction, and epithelial cell proliferation and is a potent mitogen for neoplastic tissues. The effects of GRP are mediated through the gastrin-releasing peptide receptor. This receptor is a glycosylated, 7-transmembrane G-protein coupled receptor that activates the phospholipase C signaling pathway. The receptor is aberrantly expressed in numerous cancers such as those of the lung, colon, and prostate. An individual with autism and multiple exostoses was found to have a balanced translocation between chromosome 8 and a chromosome X breakpoint located within the gastrin-releasing peptide receptor gene. [provided by RefSeq, Jul 2008]

MANE transcript

NM_005314.3

Inheritance

—

ClinVar variants

U:56B:14

Top phenotype

GRPR-related disorder

gnomAD constraint

pLI —, LoF o/e 0.28

Max pathogenic AF

—

Genomic locus

chrX:16,123,565-16,153,518

External References & Databases

Ensembl (ENSG00000126010)

Transcript & Mutation Effects

hg38 • Region Span ~30.0 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 GRPR variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 34

not providedTotal: 12

GRPR-related disorderTotal: 8

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005314.3. 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			5 clinvar	6 clinvar	3 clinvar	14
missense			48 clinvar	5 clinvar		53
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	56	11	3	70

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005314.3	RefSeq	NP_005305.1	3	MANE Select
ENST00000380289.3	Ensembl	ENSP00000369643.2	3	MANE Select
ENST00001134327.1	Ensembl	ENSP00000811099.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Calcium signaling pathway - Homo sapiens (human)
Neuroactive ligand-receptor interaction - Homo sapiens (human)
GPCRs, Other
Peptide GPCRs
GPCRs, Class A Rhodopsin-like

Biological Process

G protein-coupled receptor signaling pathway
phospholipase C-activating G protein-coupled receptor signaling pathway
neuropeptide signaling pathway
learning or memory
cell population proliferation

Molecular Function

G protein-coupled receptor activity
neuropeptide receptor activity
G protein-coupled peptide receptor activity
neuropeptide binding

Cellular Component

plasma membrane
integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000380289
Coding exons: 3
Length: 29466
Individuals with no LoFs: 125716
Homozygous LoFs: 4
Heterozygous LoFs: 3
Defined: 125723
p: 0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.725	130	155	0.836	0.0000123	2540
Missense (PolyPhen)		49	69.868	0.70132		1149
Synonymous	0.318	64	67.3	0.951	0.00000560	794
Loss of Function	1.79	2	7.17	0.279	5.26e-7	116

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000036	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000061	0.000035	rare
South Asian	0.000052	0.000033	rare
Other	0.00022	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Receptor for gastrin-releasing peptide (GRP) (PubMed:1655761). Signals via association with G proteins that activate a phosphatidylinositol-calcium second messenger system, resulting in Akt phosphorylation. Contributes to the regulation of food intake. Contributes to the perception of prurient stimuli and transmission of itch signals in the spinal cord that promote scratching behavior, but does not play a role in the perception of pain. Contributes primarily to nonhistaminergic itch sensation. Contributes to long-term fear memory, but not normal spatial memory (By similarity). {ECO:0000250|UniProtKB:P21729, ECO:0000269|PubMed:1655761}.;

Recessive Scores

pRec: 0.218

Intolerance Scores

LoFtool: 0.403
RVIS EVS: 0.11
RVIS percentile EVS: 61.73

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.404

Gene Damage Prediction

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