NECTIN1

nectin cell adhesion molecule 1, the group of Nectins and nectin-like molecules|V-set domain containing|CD molecules|C2-set domain containing

Basic information

Region (hg38): 11:119623408-119729200

Previous symbols: [ "HVEC", "ED4", "PVRL1" ]

Links

ENSG00000110400 ∙ NCBI:5818 ∙ OMIM:600644 ∙ HGNC:9706 ∙ Uniprot:Q15223 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cleft lip/palate-ectodermal dysplasia syndrome (Moderate), mode of inheritance: AR
• cleft lip/palate-ectodermal dysplasia syndrome (Strong), mode of inheritance: AR
• cleft lip/palate-ectodermal dysplasia syndrome (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cleft lip/palate-ectodermal dysplasia syndrome	AD/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	Craniofacial; Dermatologic; Musculoskeletal; Neurologic	10932188; 11559849

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NECTIN1 gene.

• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NECTIN1 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			6	24	1	31
missense			30	2		32
nonsense	1	1				2
start loss			1			1
frameshift						0
inframe indel			1		3	4
splice donor/acceptor (+/-2bp)						0
splice region				2		2
non coding			96	12	8	116
Total	1	1	134	38	12

Variants in NECTIN1

This is a list of pathogenic ClinVar variants found in the NECTIN1 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-119638121-C-T		Inborn genetic diseases	Uncertain significance (Nov 12, 2021)
11-119638122-G-A			Benign (Oct 11, 2023)
11-119638731-C-T		NECTIN1-related disorder	Likely benign (May 06, 2022)
11-119638775-G-A			Benign (Dec 31, 2019)
11-119638779-C-T			Benign (Nov 04, 2022)
11-119638780-G-A			Likely benign (Dec 31, 2019)
11-119639934-A-C		Cleft lip/palate-ectodermal dysplasia syndrome	Benign (Nov 07, 2021)
11-119639963-C-G		NECTIN1-related disorder	Likely benign (Oct 28, 2019)
11-119639976-GCT-G			Uncertain significance (Jan 08, 2024)
11-119661033-T-A		Cleft lip/palate-ectodermal dysplasia syndrome	Uncertain significance (Apr 27, 2017)
11-119661042-C-T		Cleft lip/palate-ectodermal dysplasia syndrome	Uncertain significance (Jan 12, 2018)
11-119661100-C-A		Cleft lip/palate-ectodermal dysplasia syndrome	Uncertain significance (Jan 13, 2018)
11-119661111-C-T		Cleft lip/palate-ectodermal dysplasia syndrome	Uncertain significance (Jan 13, 2018)
11-119661113-A-G		Cleft lip/palate-ectodermal dysplasia syndrome	Uncertain significance (Jan 13, 2018)
11-119661118-G-C		Cleft lip/palate-ectodermal dysplasia syndrome	Uncertain significance (Jan 12, 2018)
11-119661180-C-T		Cleft lip/palate-ectodermal dysplasia syndrome	Uncertain significance (Jan 13, 2018)
11-119661202-G-C		Cleft lip/palate-ectodermal dysplasia syndrome	Uncertain significance (Jan 12, 2018)
11-119661259-G-A		Cleft lip/palate-ectodermal dysplasia syndrome	Uncertain significance (Jan 13, 2018)
11-119661307-C-T		Cleft lip/palate-ectodermal dysplasia syndrome	Uncertain significance (Jan 12, 2018)
11-119661321-G-A		Cleft lip/palate-ectodermal dysplasia syndrome	Uncertain significance (Jan 13, 2018)
11-119661322-C-T		Cleft lip/palate-ectodermal dysplasia syndrome	Uncertain significance (Jan 12, 2018)
11-119661342-T-G		Cleft lip/palate-ectodermal dysplasia syndrome	Uncertain significance (Jan 13, 2018)
11-119661382-C-T		Cleft lip/palate-ectodermal dysplasia syndrome	Uncertain significance (Jan 12, 2018)
11-119661396-C-T		Cleft lip/palate-ectodermal dysplasia syndrome	Uncertain significance (Jan 13, 2018)
11-119661446-A-G		Cleft lip/palate-ectodermal dysplasia syndrome	Benign (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NECTIN1	protein_coding	protein_coding	ENST00000264025	6	105675

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0612	0.938	125736	0	12	125748	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.28	270	336	0.803	0.0000228	3350
Missense in Polyphen		82	120.76	0.67902		1282
Synonymous	0.669	134	144	0.929	0.0000108	1057
Loss of Function	2.99	6	20.7	0.290	0.00000115	227

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000150	0.000148
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000449	0.0000439
Middle Eastern	0.000109	0.000109
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Promotes cell-cell contacts by forming homophilic or heterophilic trans-dimers. Heterophilic interactions have been detected between NECTIN1 and NECTIN3 and between NECTIN1 and NECTIN4. Has some neurite outgrowth-promoting activity. {ECO:0000269|PubMed:21980294}.
• Disease: DISEASE: Ectodermal dysplasia, Margarita Island type (EDMI) [MIM:225060]: An autosomal recessive form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. It is a syndrome characterized by the association of cleft lip/palate, ectodermal dysplasia (sparse short and dry scalp hair, sparse eyebrows and eyelashes), and partial syndactyly of the fingers and/or toes. Two thirds of the patients do not manifest oral cleft but present with abnormal teeth and nails. {ECO:0000269|PubMed:10932188}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Non-syndromic orofacial cleft 7 (OFC7) [MIM:225060]: A birth defect consisting of cleft lips with or without cleft palate. Cleft lips are associated with cleft palate in two-third of cases. A cleft lip can occur on one or both sides and range in severity from a simple notch in the upper lip to a complete opening in the lip extending into the floor of the nostril and involving the upper gum. {ECO:0000269|PubMed:10932188}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Cell adhesion molecules (CAMs) - Homo sapiens (human);Adherens junction - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);EGFR1;Cell-cell junction organization;Nectin/Necl trans heterodimerization;Adherens junctions interactions;Cell junction organization;Cell-Cell communication;Nectin adhesion pathway (Consensus)

Recessive Scores

• pRec: 0.246

Intolerance Scores

• rvis_EVS: -0.24
• rvis_percentile_EVS: 36.31

Haploinsufficiency Scores

• pHI: 0.165
• hipred: Y
• hipred_score: 0.786
• ghis: 0.624

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Nectin1
• Phenotype: homeostasis/metabolism phenotype; craniofacial phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; vision/eye phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: lens morphogenesis in camera-type eye;desmosome organization;iron ion transport;immune response;cell adhesion;homophilic cell adhesion via plasma membrane adhesion molecules;heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules;axon guidance;virion attachment to host cell;adherens junction organization;viral entry into host cell;regulation of synapse assembly;retina development in camera-type eye;enamel mineralization;cell-cell adhesion;protein localization to cell junction
• Cellular component: extracellular region;plasma membrane;adherens junction;cell-cell adherens junction;membrane;integral component of membrane;dendrite;growth cone membrane;intracellular membrane-bounded organelle;apical junction complex;cell-cell contact zone;hippocampal mossy fiber to CA3 synapse;integral component of presynaptic active zone membrane
• Molecular function: virus receptor activity;protein binding;coreceptor activity;carbohydrate binding;signaling receptor activity;identical protein binding;protein homodimerization activity;virion binding;protein heterodimerization activity;cell adhesion molecule binding