GPR149

protein-coding

G protein-coupled receptor 149, the group of G protein-coupled receptors, Class A orphans

Gene summary

This gene encodes a seven-transmembrane G protein coupled receptor (GPCR) class A family member. Although categorized as a class A GPCR, the encoded protein lacks the first two charged amino acids of the highly conserved Asp-Arg-Tyr (DRY) motif found in the third transmembrane helix of class A receptors which is important for efficient G protein-coupled signal transduction. Mice with a knockout of the orthologous gene are viable and have normal maturation of the ovarian follicle, but show enhanced fertility and ovulation. All GPCRs have a common structural architecture consisting of seven transmembrane alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptor, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes. [provided by RefSeq, Jul 2017]

MANE transcript

NM_001038705.3

Inheritance

—

ClinVar variants

U:118B:2

Top phenotype

Hypertrophic cardiomyopathy

gnomAD constraint

pLI —, LoF o/e 0.73

Max pathogenic AF

—

Genomic locus

chr3:154,334,943-154,430,190

External References & Databases

Ensembl (ENSG00000174948)

Transcript & Mutation Effects

hg38 • Region Span ~95.2 kb

Loading mutation effect viewer...

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 GPR149 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 118

not providedTotal: 1

Hypertrophic cardiomyopathyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001038705.3. 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			1 clinvar			1
missense			117 clinvar	2 clinvar		119
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	118	2	0	120

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001038705.3	RefSeq	NP_001033794.1	4	MANE Select
ENST00000389740.3	Ensembl	ENSP00000374390.2	4	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

preantral ovarian follicle growth
antral ovarian follicle growth
neuropeptide signaling pathway
negative regulation of ovulation

Molecular Function

G protein-coupled receptor activity
melanin-concentrating hormone receptor activity
peptide binding
neuropeptide binding

Cellular Component

integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000389740
Coding exons: 4
Length: 92044
Individuals with no LoFs: 124685
Homozygous LoFs: 0
Heterozygous LoFs: 112
Defined: 124797
p: 0.000449

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.932	450	398	1.13	0.0000192	4773
Missense (PolyPhen)		138	132.48	1.0416		1638
Synonymous	-1.68	193	165	1.17	0.00000837	1505
Loss of Function	1.20	16	22.1	0.725	0.00000101	287

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00019	rare
Latino/Admixed American	0.0013	0.0013	notable
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.0011	0.0011	notable
Finnish	0	0.0	absent
European (Non-Finnish)	0.00028	0.00028	rare
South Asian	0.00027	0.00026	rare
Other	0.00034	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Orphan receptor.;

Recessive Scores

pRec: 0.0968

Intolerance Scores

LoFtool: 0.290
RVIS EVS: -0.55
RVIS percentile EVS: 19.8

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.201

Gene Damage Prediction

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