GPR146

protein-coding

G protein-coupled receptor 146, the group of G protein-coupled receptors, Class A orphans

Gene summary

Enables G protein-coupled receptor activity. Involved in adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway and regulation of cholesterol biosynthetic process. Is active in plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001303473.2

Inheritance

—

ClinVar variants

B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.34

Max pathogenic AF

—

Genomic locus

chr7:1,044,546-1,059,261

External References & Databases

Ensembl (ENSG00000164849)

Transcript & Mutation Effects

hg38 • Region Span ~14.7 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 GPR146 variants in ClinVar

1 Conditions Cataloged

not providedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001303473.2. 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				2 clinvar	2 clinvar	4
missense				2 clinvar		2
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	0	4	2	6

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 55 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001303473.2	RefSeq	NP_001290402.1	1	MANE Select
ENST00000444847.2	Ensembl	ENSP00000410743.2	1	MANE Select
NM_001303474.2	RefSeq	NP_001290403.1	1	Standard
NM_138445.4	RefSeq	NP_612454.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

G protein-coupled receptor signaling pathway

Molecular Function

G protein-coupled receptor activity

Cellular Component

plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000397095
Coding exons: 1
Length: 14686
Individuals with no LoFs: 125061
Homozygous LoFs: 0
Heterozygous LoFs: 11
Defined: 125072
p: 0.0000440

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.418	244	226	1.08	0.0000159	2091
Missense (PolyPhen)		102	91.282	1.1174		860
Synonymous	-1.50	137	116	1.18	0.00000897	758
Loss of Function	1.50	2	5.93	0.337	2.55e-7	58

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00012	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00027	0.00027	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000054	0.000035	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Orphan receptor.;

Recessive Scores

pRec: 0.114

Intolerance Scores

LoFtool: 0.630
RVIS EVS: -0.06
RVIS percentile EVS: 48.84

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.248

Gene Damage Prediction

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