Ectodermal dysplasia-syndactyly syndrome 1
disease diseaseOn this page
Also known as ectodermal dysplasia-syndactyly syndrome caused by mutation in NECTIN4EDSS1NECTIN4 ectodermal dysplasia-syndactyly syndrome
Summary
Ectodermal dysplasia-syndactyly syndrome 1 (MONDO:0024565) is a disease caused by NECTIN4 (GenCC Definitive), with 1 cohort gene.
At a glance
- Causal gene: NECTIN4 (GenCC Definitive)
- Cohort genes: 1
- ClinVar variants: 14
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | ectodermal dysplasia-syndactyly syndrome 1 |
| Mondo ID | MONDO:0024565 |
| OMIM | 613573 |
| UMLS | C3150807 |
| MedGen | 462157 |
| GARD | 0025433 |
| Is cancer (heuristic) | no |
Also known as: ectodermal dysplasia-syndactyly syndrome 1 · ectodermal dysplasia-syndactyly syndrome caused by mutation in NECTIN4 · EDSS1 · NECTIN4 ectodermal dysplasia-syndactyly syndrome
Data availability: 14 ClinVar variants · 3 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by body system or component › syndromic disease › ectodermal dysplasia syndrome › ectodermal dysplasia-syndactyly syndrome › ectodermal dysplasia-syndactyly syndrome 1
Related subtypes (1): ectodermal dysplasia-cutaneous syndactyly syndrome
Genetics & variants
GWAS landscape
No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.
Variant details and genetic-evidence tiers
ClinVar germline variants
14 retrieved; paginated sample, class counts are floors:
8 pathogenic, 4 uncertain significance, 1 likely pathogenic, 1 conflicting classifications of pathogenicity
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1600 | NM_030916.3(NECTIN4):c.851G>A (p.Arg284Gln) | NECTIN4 | Pathogenic | no assertion criteria provided |
| 1601 | NM_030916.3(NECTIN4):c.554C>T (p.Thr185Met) | NECTIN4 | Pathogenic | no assertion criteria provided |
| 1602 | NM_030916.3(NECTIN4):c.906del (p.Pro304fs) | NECTIN4 | Pathogenic | no assertion criteria provided |
| 30794 | NM_030916.3(NECTIN4):c.635C>G (p.Pro212Arg) | NECTIN4 | Pathogenic | no assertion criteria provided |
| 425551 | NM_030916.3(NECTIN4):c.724G>A (p.Val242Met) | NECTIN4 | Pathogenic | no assertion criteria provided |
| 425552 | NM_030916.3(NECTIN4):c.181C>T (p.Gln61Ter) | NECTIN4 | Pathogenic | no assertion criteria provided |
| 807665 | NM_030916.3(NECTIN4):c.229C>T (p.Gln77Ter) | NECTIN4 | Pathogenic | criteria provided, single submitter |
| 996828 | NM_030916.3(NECTIN4):c.880C>T (p.Arg294Ter) | NECTIN4 | Pathogenic | criteria provided, single submitter |
| 3393124 | NM_030916.3(NECTIN4):c.1516C>T (p.Arg506Trp) | NECTIN4 | Likely pathogenic | criteria provided, single submitter |
| 418440 | NM_030916.3(NECTIN4):c.1327C>T (p.Arg443Cys) | NECTIN4 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1029983 | NM_030916.3(NECTIN4):c.1478G>C (p.Arg493Pro) | NECTIN4 | Uncertain significance | criteria provided, single submitter |
| 1032240 | NM_030916.3(NECTIN4):c.1387C>G (p.Pro463Ala) | NECTIN4 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 2434319 | NM_030916.3(NECTIN4):c.1490C>T (p.Thr497Met) | NECTIN4 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 3774316 | NM_030916.3(NECTIN4):c.374A>C (p.Tyr125Ser) | NECTIN4 | Uncertain significance | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 4 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
GenCC gene–disease validity (cohort genes)
the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.
| Gene | Classification | Inheritance | Disease | Records |
|---|---|---|---|---|
| NECTIN4 | Definitive | Autosomal recessive | ectodermal dysplasia-syndactyly syndrome 1 | 4 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| NECTIN4 | Orphanet:247820 | Ectodermal dysplasia-pili torti-cutaneous syndactyly syndrome |
Cohort genes → proteins
1 cohort genes, 1 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 1 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| NECTIN4 | HGNC:19688 | ENSG00000143217 | Q96NY8 | Nectin-4 | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| NECTIN4 | Nectin-4 | Seems to be involved in cell adhesion through trans-homophilic and -heterophilic interactions, the latter including specifically interactions with NECTIN1. |
Protein-family classification
Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0
Family distribution
Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.
| Family | Genes | Fold | FDR |
|---|---|---|---|
| Antibody/Immunoglobulin | 1 | 29.2× | 0.034 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| NECTIN4 | Antibody/Immunoglobulin | yes | Ig_sub2, Ig_sub, Ig-like_dom |
Expression context
Cohort genes with no expression data: 0.
1 cohort gene are a single-cell marker in ≥1 SCXA experiment.
Breadth distribution (Bgee present_calls)
| Bucket | Genes |
|---|---|
| narrow (1-5 tissues) | 0 |
| moderate (6-20) | 0 |
| broad (>20) | 1 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| lower esophagus mucosa | 1 |
| skin of abdomen | 1 |
| skin of leg | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| NECTIN4 | 160 | broad | marker | lower esophagus mucosa, skin of abdomen, skin of leg |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| NECTIN4 | 871 |
Structural data
PDB: 1 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| NECTIN4 | Q96NY8 | 5 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).
Pathways by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Nectin/Necl trans heterodimerization | 1 | 1427.5× | 0.004 | NECTIN4 |
| Adherens junctions interactions | 1 | 248.3× | 0.007 | NECTIN4 |
| Cell-cell junction organization | 1 | 248.3× | 0.007 | NECTIN4 |
| Cell junction organization | 1 | 187.2× | 0.007 | NECTIN4 |
| Cell-Cell communication | 1 | 137.6× | 0.007 | NECTIN4 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| negative regulation of natural killer cell mediated cytotoxicity | 1 | 887.0× | 0.003 | NECTIN4 |
| heterophilic cell-cell adhesion | 1 | 337.0× | 0.004 | NECTIN4 |
| homophilic cell-cell adhesion | 1 | 140.4× | 0.007 | NECTIN4 |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1
Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| NECTIN4 | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| NECTIN4 | 4 | Binding:4 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 0 | |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 1 | NECTIN4 |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 0 |
Undrugged target profiles
1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| NECTIN4 | 4 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.
Related Atlas pages
- Cohort genes: NECTIN4