ADGRG2

protein-coding

adhesion G protein-coupled receptor G2, the group of Adhesion G protein-coupled receptors, subfamily G

Gene summary

This gene encodes a member of the G protein-coupled receptor family described as an epididymis-specific transmembrane protein. The encoded protein may be proteolytically processed as it contains a motif shown to be a protein scission motif in some members of this family (PMID: 11973329). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

Previous symbols:

GPR64

MANE transcript

NM_001079858.3

Inheritance

AR, XL

ClinVar variants

P:11U:295B:26

Top phenotype

Vas deferens, congenital bilateral aplasia of, X-linked

gnomAD constraint

pLI —, LoF o/e 0.17

Max pathogenic AF

—

Genomic locus

chrX:18,989,307-19,122,637

External References & Databases

Ensembl (ENSG00000173698)

Transcript & Mutation Effects

hg38 • Region Span ~133.3 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

congenital bilateral absence of vas deferensSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0018801

Submitter: Orphanet

Clinical Genomic Database (CGD)

Vas deferens, congenital bilateral aplasia of, X-linkedXL

Manifestation: Genitourinary

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 27476656

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ADGRG2 variants in ClinVar

7 Conditions Cataloged

Inborn genetic diseasesTotal: 94

not providedTotal: 13

Congenital bilateral aplasia of vas deferens from CFTR mutationTotal: 13

ADGRG2-related disorderTotal: 7

not specifiedTotal: 7

Vas deferens, congenital bilateral aplasia of, X-linkedTotal: 7

Obstructive azoospermiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001079858.3. 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			37 clinvar	10 clinvar	1 clinvar	48
missense			198 clinvar	13 clinvar	2 clinvar	213
nonsense	2 clinvar		15 clinvar			17
start loss						0
frameshift	7 clinvar	1 clinvar				8
splice donor/acceptor (+/-2bp)	1 clinvar		45 clinvar			46
Total	10	1	295	23	3	332

Highest pathogenic variant AF is 0.0000022566105

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 64 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001079858.3	RefSeq	NP_001073327.1	27	MANE Select
ENST00000379869.8	Ensembl	ENSP00000369198.3	27	MANE Select
NM_001079859.3	RefSeq	NP_001073328.1	26	Standard
NM_001079860.3	RefSeq	NP_001073329.1	25	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

GPCRs, Class B Secretin-like

Biological Process

cell surface receptor signaling pathway
G protein-coupled receptor signaling pathway
adenylate cyclase-activating G protein-coupled receptor signaling pathway
spermatogenesis

Molecular Function

G protein-coupled receptor activity

Cellular Component

cytosol
plasma membrane
integral component of plasma membrane
cell surface
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000379869
Coding exons: 27
Length: 133329
Individuals with no LoFs: 125705
Homozygous LoFs: 5
Heterozygous LoFs: 6
Defined: 125716
p: 0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.89	267	369	0.724	0.0000273	6623
Missense (PolyPhen)		73	123.79	0.58973		2383
Synonymous	0.462	139	146	0.951	0.0000114	2054
Loss of Function	4.52	6	34.8	0.172	0.00000246	639

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00015	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00016	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000040	0.000026	rare
South Asian	0.00012	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Orphan receptor. Could be involved in a signal transduction pathway controlling epididymal function and male fertility. May regulate fluid exchange within epididymis. {ECO:0000250|UniProtKB:Q8CJ12}.;
Disease: DISEASE: Congenital bilateral aplasia of the vas deferens, X- linked (CBAVDX) [MIM:300985]: A disease characterized by bilateral absence of vas deferens, obstructive azoospermia, and infertility. {ECO:0000269|PubMed:27476656}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.104

Intolerance Scores

RVIS EVS: 0.51
RVIS percentile EVS: 80.24

Essentials

Essential (gene trap): N