NECTIN3

protein-coding

nectin cell adhesion molecule 3, the group of I-set domain containing|V-set domain containing|CD molecules|C2-set domain containing|Nectins and nectin-like molecules

Gene summary

This gene encodes a member of the nectin family of proteins, which function as adhesion molecules at adherens junctions. This family member interacts with other nectin-like proteins and with afadin, a filamentous actin-binding protein involved in the regulation of directional motility, cell proliferation and survival. This gene plays a role in ocular development involving the ciliary body. Mutations in this gene are believed to result in congenital ocular defects. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

Previous symbols:

PVRL3

MANE transcript

NM_015480.3

Inheritance

—

ClinVar variants

U:7B:8

Top phenotype

NECTIN3-related disorder

gnomAD constraint

pLI —, LoF o/e 0.14

Max pathogenic AF

—

Genomic locus

chr3:111,070,071-111,275,563

External References & Databases

Ensembl (ENSG00000177707)

Transcript & Mutation Effects

hg38 • Region Span ~205.5 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 NECTIN3 variants in ClinVar

4 Conditions Cataloged

NECTIN3-related disorderTotal: 8

not specifiedTotal: 5

not providedTotal: 2

Developmental cataractTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015480.3. 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			1 clinvar	4 clinvar		5
missense			6 clinvar	1 clinvar	3 clinvar	10
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	7	5	3	15

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 28 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015480.3	RefSeq	NP_056295.1	6	MANE Select
ENST00000485303.6	Ensembl	ENSP00000418070.1	6	MANE Select
NM_001243286.2	RefSeq	NP_001230215.1	6	Standard
NM_001243288.2	RefSeq	NP_001230217.1	9	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)
Cell-cell junction organization
Nectin/Necl trans heterodimerization
Adherens junctions interactions

Biological Process

lens morphogenesis in camera-type eye
homophilic cell adhesion via plasma membrane adhesion molecules
heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules
spermatid development
fertilization

Molecular Function

protein binding
signaling receptor activity
protein homodimerization activity
cell adhesion molecule binding

Cellular Component

plasma membrane
cell-cell junction
cell-cell adherens junction
apical junction complex
cell-cell contact zone

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000485303
Coding exons: 6
Length: 205493
Individuals with no LoFs: 125740
Homozygous LoFs: 0
Heterozygous LoFs: 3
Defined: 125743
p: 0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.770	245	281	0.871	0.0000136	3541
Missense (PolyPhen)		59	97.51	0.60506		1221
Synonymous	-1.43	123	104	1.18	0.00000534	1106
Loss of Function	3.66	3	21.2	0.142	0.00000106	281

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000026	0.000026	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a role in cell-cell adhesion through heterophilic trans-interactions with nectin-like proteins or nectins, such as trans-interaction with NECTIN2 at Sertoli-spermatid junctions. Trans-interaction with PVR induces activation of CDC42 and RAC small G proteins through common signaling molecules such as SRC and RAP1. Also involved in the formation of cell-cell junctions, including adherens junctions and synapses. Induces endocytosis- mediated down-regulation of PVR from the cell surface, resulting in reduction of cell movement and proliferation. Plays a role in the morphology of the ciliary body. {ECO:0000269|PubMed:16216929}.;

Recessive Scores

pRec: 0.186

Intolerance Scores

RVIS EVS: 0.02
RVIS percentile EVS: 55.45

Essentials

Essential (gene trap): N