ADGRG4

protein-coding

adhesion G protein-coupled receptor G4, the group of Adhesion G protein-coupled receptors, subfamily G

Gene summary

This gene encodes a G-protein coupled receptor belonging to a large family of diverse integral membrane proteins that participate in various physiological functions. Members of this superfamily are characterized by a signature 7-transmembrane domain motif. The ligand for this family member is unknown, and it is therefore an orphan receptor. This receptor is known to be expressed in normal enterochromaffin cells and in gastrointestinal neuroendocrine carcinoma cells, and it is therefore considered to be a novel biomarker or target for immunotherapy. [provided by RefSeq, May 2010]

Previous symbols:

GPR112

MANE transcript

NM_153834.4

Inheritance

ClinVar variants

U:409B:56

Top phenotype

ADGRG4-related disorder

gnomAD constraint

pLI —, LoF o/e 0.92

Max pathogenic AF

—

Genomic locus

chrX:136,300,963-136,416,890

External References & Databases

Ensembl (ENSG00000156920)

Transcript & Mutation Effects

hg38 • Region Span ~115.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autism spectrum disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0005258

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ADGRG4 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 375

not providedTotal: 16

ADGRG4-related disorderTotal: 14

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_153834.4. 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			11 clinvar	11 clinvar	1 clinvar	23
missense			383 clinvar	44 clinvar		427
nonsense			7 clinvar			7
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			8 clinvar			8
Total	0	0	409	55	1	465

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 10 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_153834.4	RefSeq	NP_722576.3	23	MANE Select
ENST00000394143.6	Ensembl	ENSP00000377699.1	23	MANE Select
ENST00000370652.5	Ensembl	ENSP00000359686.1	23	Standard
ENST00000370652.6	Ensembl	ENSP00000359686.1	23	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

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

Molecular Function

G protein-coupled receptor activity

Cellular Component

integral component of plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000394143
Coding exons: 23
Length: 136094
Individuals with no LoFs: 125647
Homozygous LoFs: 30
Heterozygous LoFs: 64
Defined: 125741
p: 0.000374

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.828	1159	1.08e+3	1.07	0.0000754	19901
Missense (PolyPhen)		128	144.53	0.88563		3021
Synonymous	-1.66	453	410	1.10	0.0000299	6651
Loss of Function	0.605	55	60.1	0.916	0.00000420	1249

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00070	0.00055	rare
Latino/Admixed American	0.00032	0.00023	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0018	0.0013	notable
Finnish	0.00012	0.000092	rare
European (Non-Finnish)	0.00061	0.00042	rare
South Asian	0.00019	0.000098	rare
Other	0.00026	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Orphan receptor.;

Intolerance Scores

RVIS EVS: 0.08
RVIS percentile EVS: 59.21