Ectodermal dysplasia 9, hair/nail type

Summary

Ectodermal dysplasia 9, hair/nail type (MONDO:0013976) is a disease caused by HOXC13 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: HOXC13 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 8

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	ectodermal dysplasia 9, hair/nail type
Mondo ID	MONDO:0013976
OMIM	614931
DOID	DOID:0111656
UMLS	C3554127
MedGen	767041
GARD	0018066
Is cancer (heuristic)	no

Also known as: ECTD9 · ectodermal dysplasia 9, hair/nail type · HOXC13 pure hair and nail ectodermal dysplasia · pure hair and nail ectodermal dysplasia caused by mutation in HOXC13

Data availability: 8 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › ectodermal dysplasia syndrome › pure hair and nail ectodermal dysplasia › ectodermal dysplasia 9, hair/nail type

Related subtypes (3): ectodermal dysplasia 4, hair/nail type, ectodermal dysplasia 6, hair/nail type, ectodermal dysplasia 7, hair/nail type

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

8 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 3 pathogenic, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
39781	NM_017410.3(HOXC13):c.390C>A (p.Tyr130Ter)	HOXC13	Pathogenic	no assertion criteria provided
39782	NM_017410.2(HOXC13):c.-24497_736+2389del	HOXC13	Pathogenic	no assertion criteria provided
50641	NM_017410.3(HOXC13):c.355del (p.Leu119fs)	HOXC13	Pathogenic	no assertion criteria provided
2432525	NM_017410.3(HOXC13):c.325C>T (p.Pro109Ser)	HOXC13	Uncertain significance	criteria provided, multiple submitters, no conflicts
2689222	NM_017410.3(HOXC13):c.932G>C (p.Arg311Pro)	HOXC13	Uncertain significance	criteria provided, single submitter
3062139	NM_017410.3(HOXC13):c.720G>C (p.Trp240Cys)	HOXC13	Uncertain significance	criteria provided, single submitter
4278152	NM_017410.3(HOXC13):c.418del (p.Leu140fs)	HOXC13	Uncertain significance	criteria provided, single submitter
1285351	NM_017410.3(HOXC13):c.*12C>A	HOXC13	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
HOXC13	Definitive	Autosomal recessive	ectodermal dysplasia 9, hair/nail type	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HOXC13	Orphanet:69084	Pure hair and nail ectodermal dysplasia

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
HOXC13	HGNC:5125	ENSG00000123364	P31276	Homeobox protein Hox-C13	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HOXC13	Homeobox protein Hox-C13	Transcription factor which plays a role in hair follicle differentiation.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HOXC13	Transcription factor	no		HD, Homeodomain-like_sf, Homeobox_CS

Expression context

Cohort genes with no expression data: 0.

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
hair follicle	1
olfactory bulb	1
type B pancreatic cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HOXC13	33	broad	yes	hair follicle, type B pancreatic cell, olfactory bulb

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HOXC13	1,247

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
HOXC13	P31276	58.40

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
tongue morphogenesis	1	3370.4×	0.001	HOXC13
nail development	1	2407.4×	0.001	HOXC13
hair follicle development	1	383.0×	0.006	HOXC13
anterior/posterior pattern specification	1	181.2×	0.010	HOXC13
anatomical structure morphogenesis	1	139.3×	0.010	HOXC13
positive regulation of DNA-templated transcription	1	27.9×	0.042	HOXC13
regulation of transcription by RNA polymerase II	1	11.7×	0.086	HOXC13

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HOXC13	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	HOXC13

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)
HOXC13	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.