NECTIN4

nectin cell adhesion molecule 4, the group of V-set domain containing|C2-set domain containing|Nectins and nectin-like molecules

Basic information

Region (hg38): 1:161070998-161089558

Previous symbols: [ "PVRL4" ]

Links

ENSG00000143217 ∙ NCBI:81607 ∙ OMIM:609607 ∙ HGNC:19688 ∙ Uniprot:Q96NY8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• ectodermal dysplasia-syndactyly syndrome 1 (Moderate), mode of inheritance: AR
• ectodermal dysplasia-syndactyly syndrome (Supportive), mode of inheritance: AR
• ectodermal dysplasia-syndactyly syndrome 1 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ectodermal dysplasia-syndactyly syndrome 1	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Dental; Dermatologic; Musculoskeletal	1646587; 20691405; 21346770

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NECTIN4 gene.

• Ectodermal dysplasia-syndactyly syndrome 1 (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NECTIN4 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				21	5	26
missense			19	1	3	23
nonsense	2					2
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region			1	1	1	3
non coding				2	2	4
Total	2	1	19	24	10

Variants in NECTIN4

This is a list of pathogenic ClinVar variants found in the NECTIN4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-161072677-C-T		NECTIN4-related disorder	Uncertain significance (Jul 09, 2024)
1-161072693-T-C		Inborn genetic diseases	Uncertain significance (Aug 17, 2021)
1-161072694-G-T			Likely benign (Nov 27, 2023)
1-161072703-C-T			Likely benign (Jan 12, 2024)
1-161072704-G-A		Ectodermal dysplasia-syndactyly syndrome 1	Uncertain significance (Dec 15, 2022)
1-161072716-C-G		Ectodermal dysplasia-syndactyly syndrome 1	Uncertain significance (Jun 03, 2020)
1-161072725-C-A			Uncertain significance (Jan 13, 2024)
1-161072729-T-C			Uncertain significance (May 14, 2022)
1-161072807-G-C		Ectodermal dysplasia-syndactyly syndrome 1	Uncertain significance (Oct 28, 2022)
1-161072841-C-T			Benign (Oct 20, 2023)
1-161072847-G-A			Benign (Mar 22, 2023)
1-161072853-C-T			Likely benign (Aug 23, 2022)
1-161072856-G-A			Benign (Oct 09, 2023)
1-161072867-G-A		Ectodermal dysplasia-syndactyly syndrome 1 • NECTIN4-related disorder	Conflicting classifications of pathogenicity (Jan 18, 2024)
1-161073227-T-C		Inborn genetic diseases	Uncertain significance (Jul 10, 2022)
1-161073264-G-A			Likely benign (Mar 12, 2022)
1-161073270-C-T			Likely benign (Aug 04, 2023)
1-161073273-G-A			Likely benign (Aug 18, 2022)
1-161073293-C-T			Uncertain significance (Dec 13, 2022)
1-161073297-C-T			Benign (Nov 13, 2023)
1-161073316-C-T			Likely benign (Oct 23, 2022)
1-161073719-C-T			Likely pathogenic (Feb 05, 2018)
1-161073774-G-C			Likely benign (Feb 22, 2022)
1-161074245-G-A			Uncertain significance (Jul 19, 2022)
1-161074306-G-A			Likely benign (Jul 26, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NECTIN4	protein_coding	protein_coding	ENST00000368012	9	18605

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.835	0.165	125704	0	44	125748	0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.28	248	312	0.796	0.0000210	3243
Missense in Polyphen		56	99.97	0.56017		1028
Synonymous	0.140	139	141	0.985	0.00000996	1114
Loss of Function	3.73	4	23.5	0.170	0.00000130	239

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000701	0.000701
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000141	0.000141
Middle Eastern	0.00	0.00
South Asian	0.0000980	0.0000980
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Seems to be involved in cell adhesion through trans- homophilic and -heterophilic interactions, the latter including specifically interactions with NECTIN1. Does not act as receptor for alpha-herpesvirus entry into cells.
• Disease: DISEASE: Ectodermal dysplasia-syndactyly syndrome 1 (EDSS1) [MIM:613573]: A form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. EDSS1 is characterized by the association of hair and teeth abnormalities with cutaneous syndactyly of the hands and/or feet. Hair morphologic abnormalities include twists at irregular intervals (pilli torti) and swelling along the shafts, particularly associated with areas of breakage. Dental findings consist of abnormally widely spaced teeth, with peg- shaped and conical crowns. Patients have normal sweating. {ECO:0000269|PubMed:20691405}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Adherens junction - Homo sapiens (human);Cell-cell junction organization;Nectin/Necl trans heterodimerization;Adherens junctions interactions;Cell junction organization;Cell-Cell communication (Consensus)

Recessive Scores

• pRec: 0.126

Intolerance Scores

• rvis_EVS: -0.33
• rvis_percentile_EVS: 30.7

Haploinsufficiency Scores

• pHI: 0.153
• hipred: Y
• hipred_score: 0.598
• ghis: 0.540

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Nectin4

Gene ontology

• Biological process: homophilic cell adhesion via plasma membrane adhesion molecules;heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules;adherens junction organization;viral entry into host cell
• Cellular component: plasma membrane;cell-cell adherens junction;integral component of membrane;apical junction complex;extracellular exosome
• Molecular function: virus receptor activity;protein binding;signaling receptor activity;identical protein binding;protein homodimerization activity;cell adhesion molecule binding