VTCN1

protein-coding

V-set domain containing T cell activation inhibitor 1, the group of B7 family|V-set domain containing

Gene summary

This gene encodes a protein belonging to the B7 costimulatory protein family. Proteins in this family are present on the surface of antigen-presenting cells and interact with ligand bound to receptors on the surface of T cells. Studies have shown that high levels of the encoded protein has been correlated with tumor progression. A pseudogene of this gene is located on chromosome 20. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

MANE transcript

NM_024626.4

Inheritance

—

ClinVar variants

U:3B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.31

Max pathogenic AF

—

Genomic locus

chr1:117,143,587-117,210,960

External References & Databases

Ensembl (ENSG00000134258)

Transcript & Mutation Effects

hg38 • Region Span ~67.4 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 VTCN1 variants in ClinVar

1 Conditions Cataloged

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024626.4. 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			1 clinvar			1
missense			1 clinvar	1 clinvar		2
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	3	1	0	4

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 22 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024626.4	RefSeq	NP_078902.2	5	MANE Select
ENST00000369458.8	Ensembl	ENSP00000358470.3	5	MANE Select
NM_001253849.2	RefSeq	NP_001240778.1	3	Standard
NM_001253850.2	RefSeq	NP_001240779.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cell adhesion molecules (CAMs) - Homo sapiens (human)

Biological Process

response to protozoan
adaptive immune response
positive regulation of T cell proliferation
negative regulation of T cell proliferation
negative regulation of apoptotic process

Molecular Function

molecular_function
signaling receptor binding

Cellular Component

external side of plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000369458
Coding exons: 5
Length: 67348
Individuals with no LoFs: 125653
Homozygous LoFs: 0
Heterozygous LoFs: 95
Defined: 125748
p: 0.000378

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.861	125	155	0.805	0.00000791	1841
Missense (PolyPhen)		37	54.435	0.67971		626
Synonymous	0.180	60	61.8	0.971	0.00000330	566
Loss of Function	-0.996	16	12.2	1.31	6.03e-7	142

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.0010	0.0010	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00087	0.00087	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00013	0.00012	rare
South Asian	0.00075	0.00075	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Negatively regulates T-cell-mediated immune response by inhibiting T-cell activation, proliferation, cytokine production and development of cytotoxicity. When expressed on the cell surface of tumor macrophages, plays an important role, together with regulatory T-cells (Treg), in the suppression of tumor- associated antigen-specific T-cell immunity. Involved in promoting epithelial cell transformation. {ECO:0000250|UniProtKB:Q7TSP5, ECO:0000269|PubMed:15878339, ECO:0000269|PubMed:16606666, ECO:0000269|PubMed:17509674, ECO:0000269|PubMed:17875732}.;

Recessive Scores

pRec: 0.0858

Intolerance Scores

LoFtool: 0.754
RVIS EVS: 0.24
RVIS percentile EVS: 69.21

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0365

Gene Damage Prediction

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