PVRIG

protein-coding

PVR related immunoglobulin domain containing

Gene summary

Enables phosphatase binding activity and signaling receptor activity. Involved in negative regulation of T cell receptor signaling pathway. Located in plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001397246.1

Inheritance

—

ClinVar variants

U:53B:15

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.54

Max pathogenic AF

—

Genomic locus

chr7:100,218,241-100,221,490

External References & Databases

Ensembl (ENSG00000213413)

Transcript & Mutation Effects

hg38 • Region Span ~3.2 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 PVRIG variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 66

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001397246.1. 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			52 clinvar	15 clinvar		67
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	53	15	0	68

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001397246.1	RefSeq	NP_001384175.1	5	MANE Select
ENST00000699088.1	Ensembl	ENSP00000514123.1	5	MANE Select
NM_001387134.1	RefSeq	NP_001374063.1	5	Standard
NM_024070.3	RefSeq	NP_076975.2	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of T cell receptor signaling pathway

Molecular Function

protein binding
phosphatase binding
signaling receptor activity

Cellular Component

plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000317271
Coding exons: 5
Length: 3250
Individuals with no LoFs: 125671
Homozygous LoFs: 0
Heterozygous LoFs: 53
Defined: 125724
p: 0.000211

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0439	210	208	1.01	0.0000133	2005
Missense (PolyPhen)		92	105.82	0.86937		1214
Synonymous	-2.18	110	84.5	1.30	0.00000523	740
Loss of Function	1.29	5	9.25	0.541	4.82e-7	90

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00022	0.00018	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.00021	0.00020	rare
East Asian	0.0010	0.00087	notable
Finnish	0	0.0	absent
European (Non-Finnish)	0.00024	0.00022	rare
South Asian	0.00018	0.00016	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Cell surface receptor for NECTIN2. May act as a coinhibitory receptor that suppresses T-cell receptor-mediated signals. Following interaction with NECTIN2, inhibits T-cell proliferation. Competes with CD226 for NECTIN2-binding. {ECO:0000269|PubMed:26755705}.;

Intolerance Scores

LoFtool: 0.681
RVIS EVS: 0.82
RVIS percentile EVS: 87.99

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.257

Gene Damage Prediction

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