Isolated familial wooly hair disorder

Summary

Isolated familial wooly hair disorder (MONDO:0008686) is a disease (an umbrella term covering 6 Mondo subtypes) with 5 cohort genes. The dominant Reactome pathway is Formation of the cornified envelope (3 cohort genes).

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Umbrella term: 6 Mondo subtypes
• Cohort genes: 5
• Phenotypes (HPO): 12

Clinical features

Signs & symptoms

Clinical features (HPO)

12 HPO clinical features (Orphanet curated; top 12 by frequency):

HPO ID	Term	Frequency
HP:0002213	Fine hair	Very frequent (80-99%)
HP:0002224	Woolly hair	Very frequent (80-99%)
HP:0002299	Brittle hair	Very frequent (80-99%)
HP:0010719	Abnormality of hair texture	Very frequent (80-99%)
HP:0002217	Slow-growing hair	Frequent (30-79%)
HP:0005599	Hypopigmentation of hair	Frequent (30-79%)
HP:0000479	Abnormal retinal morphology	Occasional (5-29%)
HP:0000486	Strabismus	Occasional (5-29%)
HP:0000518	Cataract	Occasional (5-29%)
HP:0000615	Abnormal pupil morphology	Occasional (5-29%)
HP:0002231	Sparse body hair	Occasional (5-29%)
HP:0005338	Sparse lateral eyebrow	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	isolated familial wooly hair disorder
Mondo ID	MONDO:0008686
MeSH	C536745
Orphanet	170
DOID	DOID:0111572
SNOMED CT	52564001
UMLS	C0343073
MedGen	87469
GARD	0005597
MedDRA	10048017
Is cancer (heuristic)	no

Also known as: ADWH · familial woolly hair (autosomal recessive) · familial woolly hair syndrome · familial wooly hair (autosomal recessive) · familial wooly hair syndrome · hereditary woolly hair (autosomal dominant) · hereditary woolly hair syndrome · hereditary wooly hair (autosomal dominant) · hereditary wooly hair syndrome · woolly hair · woolly hair syndrome · woolly hair, autosomal dominant · wooly hair · wooly hair syndrome · wooly hair, autosomal dominant

Data availability: 5 GenCC gene-disease records · 1 HPO phenotype.

Disease family

An umbrella term covering 6 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › disorder of pilosebaceous unit › hair anomaly › isolated familial wooly hair disorder

Related subtypes (7): alopecia, ringed hair disease, trichodysplasia-xeroderma syndrome, uncombable hair syndrome, pili torti, pili bifurcati, pili gemini

Subtypes (6): hypotrichosis 8, hypotrichosis 7, hypotrichosis 13, wooly hair, autosomal recessive 3, autosomal dominant wooly hair, wooly hair, autosomal recessive 1, with or without hypotrichosis

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: 29 · Orphanet: 9 · 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
KRT25	Strong	Autosomal recessive	wooly hair, autosomal recessive 3	5
KRT74	Strong	Autosomal dominant	autosomal dominant wooly hair	8
LPAR6	Strong	Autosomal recessive	wooly hair, autosomal recessive 1, with or without hypotrichosis	6
KRT71	Supportive	Autosomal dominant	isolated familial wooly hair disorder	5
LIPH	Supportive	Autosomal dominant	isolated familial wooly hair disorder	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LPAR6	Orphanet:170	Woolly hair
LPAR6	Orphanet:55654	Hypotrichosis simplex
LIPH	Orphanet:170	Woolly hair
LIPH	Orphanet:55654	Hypotrichosis simplex
KRT71	Orphanet:170	Woolly hair
KRT74	Orphanet:170	Woolly hair
KRT74	Orphanet:69084	Pure hair and nail ectodermal dysplasia
KRT74	Orphanet:90368	Hypotrichosis simplex of the scalp
KRT25	Orphanet:170	Woolly hair

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
LPAR6	HGNC:15520	ENSG00000139679	P43657	Lysophosphatidic acid receptor 6	gencc
LIPH	HGNC:18483	ENSG00000163898	Q8WWY8	Lipase member H	gencc
KRT71	HGNC:28927	ENSG00000139648	Q3SY84	Keratin, type II cytoskeletal 71	gencc
KRT74	HGNC:28929	ENSG00000170484	Q7RTS7	Keratin, type II cytoskeletal 74	gencc
KRT25	HGNC:30839	ENSG00000204897	Q7Z3Z0	Keratin, type I cytoskeletal 25	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LPAR6	Lysophosphatidic acid receptor 6	Binds to oleoyl-L-alpha-lysophosphatidic acid (LPA).
LIPH	Lipase member H	Hydrolyzes specifically phosphatidic acid (PA) to produce 2-acyl lysophosphatidic acid (LPA; a potent bioactive lipid mediator) and fatty acid.
KRT71	Keratin, type II cytoskeletal 71	Plays a central role in hair formation.
KRT74	Keratin, type II cytoskeletal 74	Has a role in hair formation.
KRT25	Keratin, type I cytoskeletal 25	Essential for the proper assembly of type I and type II keratin protein complexes and formation of keratin intermediate filaments in the inner root sheath (irs).

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 3 · Druggable fraction: 0.4

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
GPCR	1	4.8×	0.530
Enzyme (other)	1	2.4×	0.530
Other/Unknown	3	1.1×	0.608

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LPAR6	GPCR	yes		GPCR_Rhodpsn, GPCR_Rhodpsn_7TM
LIPH	Enzyme (other)	yes	3.1.1.32	TAG_lipase, Lipase, Lipase_LIPH
KRT71	Other/Unknown	no		Keratin_II, IF_conserved, Keratin_2_head
KRT74	Other/Unknown	no		Keratin_II, IF_conserved, Keratin_2_head
KRT25	Other/Unknown	no		Keratin_I, IF_rod_dom

Expression context

Cohort genes with no expression data: 0.

3 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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
upper arm skin	3
skin of hip	2
male germ line stem cell (sensu Vertebrata) in testis	2
gingiva	1
gingival epithelium	1
lower esophagus mucosa	1
buccal mucosa cell	1
pancreatic ductal cell	1
rectum	1
nipple	1
tibialis anterior	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LPAR6	269	ubiquitous	marker	gingival epithelium, gingiva, lower esophagus mucosa
LIPH	187	broad	marker	buccal mucosa cell, rectum, pancreatic ductal cell
KRT71	48	tissue_specific	yes	upper arm skin, skin of hip, nipple
KRT74	40	tissue_specific	yes	upper arm skin, male germ line stem cell (sensu Vertebrata) in testis, tibialis anterior
KRT25	70	tissue_specific	marker	upper arm skin, skin of hip, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 7.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KRT25	986
LPAR6	822
KRT71	700
LIPH	635
KRT74	451

Intra-cohort edges

A	B	Sources
KRT25	KRT71	biogrid_interaction, intact
KRT25	KRT74	biogrid_interaction, intact
KRT25	LIPH	string_interaction
KRT25	LPAR6	string_interaction
KRT74	LIPH	string_interaction
KRT74	LPAR6	string_interaction
LIPH	LPAR6	string_interaction

Structural data

PDB: 1 · AlphaFold-only: 4 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
LPAR6	P43657	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LIPH	Q8WWY8	90.89
KRT25	Q7Z3Z0	75.88
KRT71	Q3SY84	72.66
KRT74	Q7RTS7	72.11

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. Enrichment computed across 5 evidence-associated genes (5 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 5 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	3	52.7×	2e-04	KRT71, KRT74, KRT25
Keratinization	3	33.4×	4e-04	KRT71, KRT74, KRT25
Nucleotide-like (purinergic) receptors	1	380.7×	0.012	LPAR6
Developmental Biology	3	8.7×	0.012	KRT71, KRT74, KRT25
P2Y receptors	1	190.3×	0.017	LPAR6
Glycerophospholipid biosynthesis	1	67.2×	0.039	LIPH
Synthesis of PA	1	58.6×	0.039	LIPH
Phospholipid metabolism	1	40.1×	0.049	LIPH
Class A/1 (Rhodopsin-like receptors)	1	14.8×	0.117	LPAR6
GPCR ligand binding	1	12.8×	0.121	LPAR6
G alpha (q) signalling events	1	11.5×	0.122	LPAR6
GPCR downstream signalling	1	8.7×	0.146	LPAR6
Signaling by GPCR	1	8.0×	0.146	LPAR6
Metabolism of lipids	1	6.3×	0.170	LIPH
Metabolism	1	2.3×	0.387	LIPH
Signal Transduction	1	2.0×	0.404	LPAR6

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 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	3	144.4×	8e-06	KRT71, KRT74, KRT25
hair follicle morphogenesis	2	198.3×	2e-04	KRT71, KRT25
keratinization	2	93.6×	7e-04	KRT71, KRT74
hair cycle	1	187.2×	0.013	KRT25
intermediate filament cytoskeleton organization	1	187.2×	0.013	KRT74
blastocyst hatching	1	108.7×	0.017	LPAR6
phosphatidic acid biosynthetic process	1	102.1×	0.017	LIPH
morphogenesis of an epithelium	1	68.8×	0.022	KRT25
lipid catabolic process	1	48.9×	0.027	LIPH
epithelial cell differentiation	1	35.1×	0.034	KRT25
cytoskeleton organization	1	26.5×	0.040	KRT25
G protein-coupled receptor signaling pathway	1	7.2×	0.131	LPAR6

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 5

Druggability breadth: 1 of 5 evidence-associated genes (20%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
LPAR6	0	0
LIPH	0	0
KRT71	0	0
KRT74	0	0
KRT25	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
LPAR6	5	Binding:4, Functional:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
LIPH	3.1.1.32	phospholipase A1

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; 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	LPAR6
D	Druggable family + AlphaFold only, no drug	1	LIPH
E	Difficult family or no structure, no drug	3	KRT71, KRT74, KRT25

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
LPAR6	5	—
LIPH	0	—
KRT71	0	—
KRT74	0	—
KRT25	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.