Ectodermal dysplasia 4, hair/nail type

Summary

Ectodermal dysplasia 4, hair/nail type (MONDO:0011177) is a disease caused by KRT85 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: KRT85 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	ectodermal dysplasia 4, hair/nail type
Mondo ID	MONDO:0011177
MeSH	C566592
OMIM	602032
DOID	DOID:0111658
UMLS	C4024880
MedGen	870434
GARD	0018062
Is cancer (heuristic)	no

Also known as: ECTD4 · ectodermal dysplasia 4, hair/nail type · KRT85 pure hair and nail ectodermal dysplasia · pili torti onychodysplasia · pure hair and nail ectodermal dysplasia caused by mutation in KRT85 · twisted hair with nail dysplasias

Data availability: 6 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 4, hair/nail type

Related subtypes (3): ectodermal dysplasia 6, hair/nail type, ectodermal dysplasia 7, hair/nail type, ectodermal dysplasia 9, 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

6 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 1 pathogenic, 1 benign/likely benign, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
102444	NM_002283.4(KRT85):c.1448_1449del (p.Pro483fs)	KRT85	Pathogenic	no assertion criteria provided
96741	NM_175053.4(KRT74):c.821T>C (p.Phe274Ser)	KRT74	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3676528	NC_000012.12:g.52364961CTT[2]	KRT85	Uncertain significance	criteria provided, multiple submitters, no conflicts
4279721	NM_002283.4(KRT85):c.538C>T (p.Arg180Trp)	KRT85	Uncertain significance	criteria provided, single submitter
638425	NM_002283.4(KRT85):c.823T>C (p.Ser275Pro)	KRT85	Uncertain significance	criteria provided, single submitter
6836	NM_002283.4(KRT85):c.233G>A (p.Arg78His)	KRT85	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 4 · 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
KRT85	Definitive	Autosomal recessive	ectodermal dysplasia 4, hair/nail type	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KRT85	Orphanet:69084	Pure hair and nail ectodermal dysplasia
KRT74	Orphanet:170	Woolly hair
KRT74	Orphanet:69084	Pure hair and nail ectodermal dysplasia
KRT74	Orphanet:90368	Hypotrichosis simplex of the scalp

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
KRT85	HGNC:6462	ENSG00000135443	P78386	Keratin, type II cuticular Hb5	gencc,clinvar
KRT74	HGNC:28929	ENSG00000170484	Q7RTS7	Keratin, type II cytoskeletal 74	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KRT74	Keratin, type II cytoskeletal 74	Has a role in hair formation.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KRT85	Other/Unknown	no		Keratin_II, IF_conserved, Keratin_2_head
KRT74	Other/Unknown	no		Keratin_II, IF_conserved, Keratin_2_head

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
upper arm skin	2
male germ cell	1
sperm	1
male germ line stem cell (sensu Vertebrata) in testis	1
tibialis anterior	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KRT85	100	tissue_specific	yes	upper arm skin, sperm, male germ cell
KRT74	40	tissue_specific	yes	upper arm skin, male germ line stem cell (sensu Vertebrata) in testis, tibialis anterior

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KRT85	626
KRT74	451

Structural data

PDB: 0 · AlphaFold-only: 2 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
KRT85	P78386	74.09
KRT74	Q7RTS7	72.11

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Formation of the cornified envelope	2	87.8×	4e-04	KRT85, KRT74
Keratinization	2	55.7×	5e-04	KRT85, KRT74
Developmental Biology	2	14.5×	0.005	KRT85, KRT74

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
intermediate filament organization	2	240.7×	4e-05	KRT85, KRT74
keratinization	2	234.1×	4e-05	KRT85, KRT74
intermediate filament cytoskeleton organization	1	468.1×	0.003	KRT74
epidermis development	1	105.3×	0.009	KRT85

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KRT85	0	0
KRT74	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
KRT85	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	2	KRT85, KRT74

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
KRT85	1	—
KRT74	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.