GPR75

protein-coding

G protein-coupled receptor 75, the group of G protein-coupled receptors, Class A orphans

Gene summary

GPR75 is a member of the G protein-coupled receptor family. GPRs are cell surface receptors that activate guanine-nucleotide binding proteins upon the binding of a ligand.[supplied by OMIM, Jul 2002]

MANE transcript

NM_006794.4

Inheritance

—

ClinVar variants

U:79B:10

Top phenotype

GPR75-related disorder

gnomAD constraint

pLI —, LoF o/e 0.71

Max pathogenic AF

—

Genomic locus

chr2:53,852,912-53,859,967

External References & Databases

Ensembl (ENSG00000119737)

Transcript & Mutation Effects

hg38 • Region Span ~7.1 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 GPR75 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 80

GPR75-related disorderTotal: 9

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006794.4. 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	1 clinvar	6
missense			79 clinvar	1 clinvar	3 clinvar	83
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	79	6	4	89

Loading ClinVar variants...

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_006794.4	RefSeq	NP_006785.1	1	MANE Select
ENST00000394705.3	Ensembl	ENSP00000378195.2	1	MANE Select
ENST00001144766.1	Ensembl	ENSP00000811744.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

GPCRs, Class A Rhodopsin-like

Biological Process

G protein-coupled receptor signaling pathway
chemokine-mediated signaling pathway
regulation of neuron death

Molecular Function

G protein-coupled receptor activity
C-C chemokine receptor activity

Cellular Component

integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000394705
Coding exons: 1
Length: 7077
Individuals with no LoFs: 125702
Homozygous LoFs: 0
Heterozygous LoFs: 46
Defined: 125748
p: 0.000183

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0359	292	290	1.01	0.0000155	3540
Missense (PolyPhen)		87	113.31	0.76779		1397
Synonymous	-1.62	141	119	1.19	0.00000665	1125
Loss of Function	0.969	9	12.7	0.707	7.80e-7	159

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00018	0.00018	rare
South Asian	0.00026	0.00026	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: G protein-coupled receptor that is activated by the chemokine CCL5/RANTES. Probably coupled to heterotrimeric Gq proteins, it stimulates inositol trisphosphate production and calcium mobilization upon activation. Together with CCL5/RANTES, may play a role in neuron survival through activation of a downstream signaling pathway involving the PI3, Akt and MAP kinases. CCL5/RANTES may also regulate insulin secretion by pancreatic islet cells through activation of this receptor. {ECO:0000250|UniProtKB:Q6X632, ECO:0000303|PubMed:23979485}.;

Recessive Scores

pRec: 0.108

Intolerance Scores

LoFtool: 0.686
RVIS EVS: -0.35
RVIS percentile EVS: 29.43

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.192

Gene Damage Prediction

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