NECTIN1

Chr 11AR

nectin cell adhesion molecule 1

Also known as: CD111, CLPED1, ED4, HIgR, HV1S, HVEC, OFC7, PRR

NCBI Gene: 5818 ENSG00000110400 UniProt: Q15223 OMIM: 600644

This cell adhesion molecule promotes cell-cell contacts and plays important roles in nervous system development, axon guidance, and synaptogenesis, as well as enamel mineralization. Autosomal recessive mutations cause cleft lip/palate-ectodermal dysplasia syndrome and orofacial cleft 7, which primarily affect craniofacial development and ectodermal structures. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.572).

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes an adhesion protein that plays a role in the organization of adherens junctions and tight junctions in epithelial and endothelial cells. The protein is a calcium(2+)-independent cell-cell adhesion molecule that belongs to the immunoglobulin superfamily and has 3 extracellular immunoglobulin-like loops, a single transmembrane domain (in some isoforms), and a cytoplasmic region. This protein acts as a receptor for glycoprotein D (gD) of herpes simplex viruses 1 and 2 (HSV-1, HSV-2), and pseudorabies virus (PRV) and mediates viral entry into epithelial and neuronal cells. Mutations in this gene cause cleft lip and palate/ectodermal dysplasia 1 syndrome (CLPED1) as well as non-syndromic cleft lip with or without cleft palate (CL/P). Alternative splicing results in multiple transcript variants encoding proteins with distinct C-termini. [provided by RefSeq, Oct 2009]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Cleft lip/palate-ectodermal dysplasia syndromeMIM #225060

Orofacial cleft 7MIM #225060

UniProtNon-syndromic orofacial cleft 7

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · cleft lip/palate-ectodermal dysplasia syndrome · AR · ClinGen 2024

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.57

LOEUF

LOF

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.57LOEUF

pLI 0.061

Z-score 2.99

OE 0.29 (0.16–0.57)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.28Z-score

OE missense 0.80 (0.73–0.89)

270 obs / 336.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.29 (0.16–0.57)

0≤0.351.4

Missense OE?0.80 (0.73–0.89)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 6 / 20.7Missense obs/exp: 270 / 336.2Syn Z: 0.67

Background carrier burden — how many people carry a rare variant somewhere in NECTIN1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 73

839 rare PASS variants

Rare truncating (LoF)

1 in 2,600

79 rare PASS variants

Rare synonymous (reference)

1 in 68

373 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for NECTIN1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 79	1 in 3,100
South Asian	~43k	1 in 54	1 in 4,800
Remaining (unassigned)	~30k	1 in 69	1 in 2,500
European (Finnish)	~27k	1 in 160	≈ 1 in 13,000
Admixed American	~22k	1 in 52	1 in 1,500
African / African American	~21k	1 in 59	1 in 680
East Asian	~20k	1 in 74	1 in 570
Ashkenazi Jewish	~13k	1 in 220	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 50	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 6 coding exons well covered in gnomAD exomes and genomes.? see exons ↓