NECTIN2

protein-coding

nectin cell adhesion molecule 2, the group of V-set domain containing|CD molecules|C2-set domain containing|Nectins and nectin-like molecules

Gene summary

This gene encodes a single-pass type I membrane glycoprotein with two Ig-like C2-type domains and an Ig-like V-type domain. This protein is one of the plasma membrane components of adherens junctions. It also serves as an entry for certain mutant strains of herpes simplex virus and pseudorabies virus, and it is involved in cell to cell spreading of these viruses. Variations in this gene have been associated with differences in the severity of multiple sclerosis. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

Previous symbols:

HVEB
PVRL2

MANE transcript

NM_001042724.2

Inheritance

—

ClinVar variants

U:13B:22

Top phenotype

NECTIN2-related disorder

gnomAD constraint

pLI —, LoF o/e 0.12

Max pathogenic AF

—

Genomic locus

chr19:44,846,175-44,889,223

External References & Databases

Ensembl (ENSG00000130202)

Transcript & Mutation Effects

hg38 • Region Span ~43.0 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 NECTIN2 variants in ClinVar

4 Conditions Cataloged

NECTIN2-related disorderTotal: 30

not providedTotal: 10

not specifiedTotal: 3

Cerebral palsyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001042724.2. 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	3 clinvar	14
missense			6 clinvar	4 clinvar	4 clinvar	14
nonsense			2 clinvar			2
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	13	15	7	35

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 47 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001042724.2	RefSeq	NP_001036189.1	9	MANE Select
ENST00000252483.10	Ensembl	ENSP00000252483.4	9	MANE Select
NM_002856.3	RefSeq	NP_002847.1	6	Standard
ENST00000252485.8	Ensembl	ENSP00000252485.3	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cell adhesion molecules (CAMs) - Homo sapiens (human)
Adherens junction - Homo sapiens (human)
Herpes simplex infection - Homo sapiens (human)
Monoamine Transport
Immune System

Biological Process

acrosome assembly
positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target
positive regulation of immunoglobulin mediated immune response
cytoskeleton organization
homophilic cell adhesion via plasma membrane adhesion molecules

Molecular Function

virus receptor activity
protein binding
coreceptor activity
identical protein binding
protein homodimerization activity

Cellular Component

plasma membrane
cell-cell junction
zonula adherens
focal adhesion
cell surface

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000252483
Coding exons: 9
Length: 43054
Individuals with no LoFs: 124796
Homozygous LoFs: 0
Heterozygous LoFs: 4
Defined: 124800
p: 0.0000160

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.64	241	324	0.743	0.0000199	3398
Missense (PolyPhen)		54	100.88	0.53531		1019
Synonymous	0.596	134	143	0.937	0.00000938	1182
Loss of Function	3.97	3	24.0	0.125	0.00000144	242

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000065	0.000065	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000056	0.000056	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Modulator of T-cell signaling. Can be either a costimulator of T-cell function, or a coinhibitor, depending on the receptor it binds to. Upon binding to CD226, stimulates T-cell proliferation and cytokine production, including that of IL2, IL5, IL10, IL13, and IFNG. Upon interaction with PVRIG, inhibits T-cell proliferation. These interactions are competitive (PubMed:26755705). Probable cell adhesion protein (PubMed:9657005). {ECO:0000269|PubMed:26755705, ECO:0000269|PubMed:9657005}.;

Recessive Scores

pRec: 0.175

Intolerance Scores

RVIS EVS: 0.56
RVIS percentile EVS: 81.63

Essentials

Essential (gene trap): N