Marie Unna hereditary hypotrichosis

Summary

Marie Unna hereditary hypotrichosis (MONDO:0018631) is a disease with 2 cohort genes.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 2
• Phenotypes (HPO): 5

Clinical features

Signs & symptoms

Clinical features (HPO)

5 HPO clinical features (Orphanet curated; top 5 by frequency):

HPO ID	Term	Frequency
HP:0001596	Alopecia	Very frequent (80-99%)
HP:0002208	Coarse hair	Very frequent (80-99%)
HP:0002209	Sparse scalp hair	Very frequent (80-99%)
HP:0100840	Aplasia/Hypoplasia of the eyebrow	Very frequent (80-99%)
HP:0200102	Sparse or absent eyelashes	Very frequent (80-99%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Marie Unna hereditary hypotrichosis
Mondo ID	MONDO:0018631
MeSH	C535912
Orphanet	444
UMLS	C2931059
MedGen	419706
GARD	0003390
Is cancer (heuristic)	no

Also known as: HR hypotrichosis · hypotrichosis caused by mutation in HR · hypotrichosis, Marie Unna type · Marie Unna congenital hypotrichosis · MUHH

Data availability: 2 GenCC gene-disease records.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › disorder of pilosebaceous unit › hypotrichosis › Marie Unna hereditary hypotrichosis

Related subtypes (18): hypotrichosis of eyelid, hypotrichosis 2, hypotrichosis 8, congenital hypotrichosis with juvenile macular dystrophy, hypotrichosis 7, hypotrichosis 1, hypotrichosis 6, hypotrichosis 3, hypotrichosis 9, hypotrichosis 10, hypotrichosis 11, hypotrichosis 12, hypotrichosis 13, Basaran Yilmaz syndrome, congenital hypotrichosis milia, hypotrichosis 14, hypotrichosis 15, hypotrichosis 16

Subtypes (2): hypotrichosis 5, hypotrichosis 4

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · 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
HR	Strong	Autosomal dominant	hypotrichosis 4	10
EPS8L3	Supportive	Autosomal dominant	Marie Unna hereditary hypotrichosis	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
EPS8L3	Orphanet:444	Marie Unna hereditary hypotrichosis
HR	Orphanet:444	Marie Unna hereditary hypotrichosis
HR	Orphanet:701	Alopecia universalis
HR	Orphanet:86819	Atrichia with papular lesions

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
EPS8L3	HGNC:21297	ENSG00000198758	Q8TE67	Epidermal growth factor receptor kinase substrate 8-like protein 3	gencc
HR	HGNC:5172	ENSG00000168453	O43593	Lysine-specific demethylase hairless	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HR	Lysine-specific demethylase hairless	Histone demethylase that specifically demethylates both mono- and dimethylated ‘Lys-9’ of histone H3.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.5

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
Scaffold/PPI	1	8.6×	0.160
Enzyme (other)	1	6.0×	0.160

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
EPS8L3	Scaffold/PPI	no		SH3_domain, PH-like_dom_sf, PTB
HR	Enzyme (other)	yes	1.14.11.65	JmjC_dom, LSDs-like

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ileal mucosa	1
mucosa of transverse colon	1
rectum	1
skin of abdomen	1
skin of leg	1
zone of skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EPS8L3	161	tissue_specific	marker	mucosa of transverse colon, rectum, ileal mucosa
HR	235	broad	marker	skin of abdomen, skin of leg, zone of skin

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EPS8L3	632
HR	559

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
EPS8L3	Q8TE67	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
HR	O43593	55.65

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of hair cycle	1	1203.7×	0.004	EPS8L3
positive regulation of ruffle assembly	1	495.6×	0.005	EPS8L3
regulation of Rho protein signal transduction	1	255.3×	0.007	EPS8L3
Rho protein signal transduction	1	123.9×	0.010	EPS8L3
regulation of transcription by RNA polymerase II	1	5.8×	0.164	HR

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 2 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
EPS8L3	0	0
HR	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
HR	1.14.11.65	[histone H3]-dimethyl-L-lysine9 demethylase

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	1	HR
E	Difficult family or no structure, no drug	1	EPS8L3

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)
EPS8L3	0	—
HR	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.