Wooly hair, autosomal recessive 1, with or without hypotrichosis

Summary

Wooly hair, autosomal recessive 1, with or without hypotrichosis (MONDO:0800312) is a disease caused by LPAR6 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: LPAR6 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	wooly hair, autosomal recessive 1, with or without hypotrichosis
Mondo ID	MONDO:0800312
UMLS	C1848435
MedGen	341227
GARD	0026495
Is cancer (heuristic)	no

Also known as: ARWH1

Data availability: 3 ClinVar variants · 1 GenCC gene-disease record.

Disease family

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 › wooly hair, autosomal recessive 1, with or without hypotrichosis

Related subtypes (5): hypotrichosis 8, hypotrichosis 7, hypotrichosis 13, wooly hair, autosomal recessive 3, autosomal dominant wooly hair

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

3 retrieved; paginated sample, class counts are floors:

1 pathogenic, 1 pathogenic/likely pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1323245	NM_000321.3(RB1):c.1695+30914_1695+30917dup	LPAR6	Pathogenic	criteria provided, multiple submitters, no conflicts
1827	NM_001162498.3(LPAR6):c.562A>T (p.Ile188Phe)	RB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4073585	NM_001162498.3(LPAR6):c.84del (p.Phe28fs)	LPAR6	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 7 · 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
LPAR6	Strong	Autosomal recessive	hypotrichosis 8	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LPAR6	Orphanet:170	Woolly hair
LPAR6	Orphanet:55654	Hypotrichosis simplex
RB1	Orphanet:1587	Monosomy 13q14 syndrome
RB1	Orphanet:357027	Hereditary retinoblastoma
RB1	Orphanet:357034	Non-hereditary retinoblastoma
RB1	Orphanet:668	Osteosarcoma
RB1	Orphanet:70573	Small cell lung cancer

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
LPAR6	HGNC:15520	ENSG00000139679	P43657	Lysophosphatidic acid receptor 6	gencc,clinvar
RB1	HGNC:9884	ENSG00000139687	P06400	Retinoblastoma-associated protein	clinvar

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).
RB1	Retinoblastoma-associated protein	Tumor suppressor that is a key regulator of the G1/S transition of the cell cycle.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · 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
GPCR	1	12.0×	0.164
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LPAR6	GPCR	yes		GPCR_Rhodpsn, GPCR_Rhodpsn_7TM
RB1	Other/Unknown	no		RB_B, RB_A, Cyclin-like_dom

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
gingiva	1
gingival epithelium	1
lower esophagus mucosa	1
choroid plexus epithelium	1
epithelium of nasopharynx	1
visceral pleura	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
RB1	287	ubiquitous	marker	epithelium of nasopharynx, choroid plexus epithelium, visceral pleura

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RB1	4,374
LPAR6	822

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RB1	P06400	19
LPAR6	P43657	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 26. 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
Defective translocation of RB1 mutants to the nucleus	1	5710.0×	0.005	RB1
Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes	1	1427.5×	0.005	RB1
Replication of the SARS-CoV-1 genome	1	1427.5×	0.005	RB1
Replication of the SARS-CoV-2 genome	1	1427.5×	0.005	RB1
Nucleotide-like (purinergic) receptors	1	951.7×	0.005	LPAR6
P2Y receptors	1	475.8×	0.008	LPAR6
Positive Regulation of CDH1 Gene Transcription	1	475.8×	0.008	RB1
Inhibition of replication initiation of damaged DNA by RB1/E2F1	1	407.9×	0.008	RB1
Formation of Senescence-Associated Heterochromatin Foci (SAHF)	1	335.9×	0.008	RB1
Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)	1	317.2×	0.008	RB1
Aberrant regulation of mitotic exit in cancer due to RB1 defects	1	259.6×	0.009	RB1
RUNX2 regulates osteoblast differentiation	1	228.4×	0.009	RB1
Oncogene Induced Senescence	1	167.9×	0.011	RB1
Nuclear events stimulated by ALK signaling in cancer	1	163.1×	0.011	RB1
Cyclin E associated events during G1/S transition	1	142.8×	0.012	RB1
Cyclin A:Cdk2-associated events at S phase entry	1	132.8×	0.012	RB1
Cyclin D associated events in G1	1	116.5×	0.013	RB1
APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1	1	85.2×	0.017	RB1
Condensation of Prophase Chromosomes	1	78.2×	0.017	RB1
MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis	1	41.4×	0.031	RB1
Class A/1 (Rhodopsin-like receptors)	1	37.1×	0.033	LPAR6
GPCR ligand binding	1	32.1×	0.037	LPAR6
G alpha (q) signalling events	1	28.7×	0.039	LPAR6
GPCR downstream signalling	1	21.7×	0.049	LPAR6
Signaling by GPCR	1	20.0×	0.051	LPAR6
Signal Transduction	1	5.1×	0.187	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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
sister chromatid biorientation	1	2808.7×	0.004	RB1
glial cell apoptotic process	1	2808.7×	0.004	RB1
maintenance of mitotic sister chromatid cohesion	1	2106.5×	0.004	RB1
regulation of lipid kinase activity	1	2106.5×	0.004	RB1
positive regulation of extracellular matrix organization	1	2106.5×	0.004	RB1
positive regulation of collagen fibril organization	1	2106.5×	0.004	RB1
negative regulation of myofibroblast differentiation	1	2106.5×	0.004	RB1
negative regulation of hepatocyte apoptotic process	1	1404.3×	0.005	RB1
enucleate erythrocyte differentiation	1	1053.2×	0.005	RB1
protein localization to chromosome, centromeric region	1	1053.2×	0.005	RB1
positive regulation of transcription regulatory region DNA binding	1	1053.2×	0.005	RB1
negative regulation of glial cell proliferation	1	842.6×	0.006	RB1
cell morphogenesis involved in neuron differentiation	1	766.0×	0.006	RB1
positive regulation of macrophage differentiation	1	601.9×	0.006	RB1
positive regulation of mitotic metaphase/anaphase transition	1	601.9×	0.006	RB1
hepatocyte apoptotic process	1	526.6×	0.007	RB1
striated muscle cell differentiation	1	495.6×	0.007	RB1
glial cell proliferation	1	443.5×	0.007	RB1
negative regulation of protein kinase activity	1	421.3×	0.007	RB1
myoblast differentiation	1	421.3×	0.007	RB1
neuron maturation	1	401.2×	0.007	RB1
chromosome organization	1	290.6×	0.008	RB1
tissue homeostasis	1	280.9×	0.008	RB1
negative regulation of apoptotic signaling pathway	1	280.9×	0.008	RB1
blastocyst hatching	1	271.8×	0.008	LPAR6
digestive tract development	1	263.3×	0.008	RB1
negative regulation of smoothened signaling pathway	1	227.7×	0.009	RB1
aortic valve morphogenesis	1	216.1×	0.010	RB1
negative regulation of G1/S transition of mitotic cell cycle	1	179.3×	0.011	RB1
skeletal muscle cell differentiation	1	172.0×	0.011	RB1

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 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
RB1	1	2
LPAR6	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
EBVACICLIB	2	RB1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
RB1	59	Binding:59
LPAR6	5	Binding:4, Functional: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

1 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.

Compound	Max phase	Cohort target (bioactivity)
EBVACICLIB	2	RB1

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	1	RB1
C	Druggable family + PDB, no drug	1	LPAR6
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)
LPAR6	5	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.