Hypotrichosis 1

Summary

Hypotrichosis 1 (MONDO:0011549) is a disease caused by APCDD1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: APCDD1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hypotrichosis 1
Mondo ID	MONDO:0011549
OMIM	605389
DOID	DOID:0110698
UMLS	C4551976
MedGen	1644234
GARD	0024806
Is cancer (heuristic)	no

Also known as: APCDD1 hypotrichosis · hereditary generalised hypotrichosis simplex · HHS · HTS · hypotrichosis 1 · hypotrichosis caused by mutation in APCDD1 · hypotrichosis type 1 · HYPT1

Data availability: 6 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › disorder of pilosebaceous unit › hypotrichosis › hypotrichosis 1

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

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:

4 uncertain significance, 1 pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
3161	NM_153000.5(APCDD1):c.26T>G (p.Leu9Arg)	APCDD1	Pathogenic	no assertion criteria provided
2148074	NM_153000.5(APCDD1):c.877G>A (p.Gly293Arg)	APCDD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2184704	NM_153000.5(APCDD1):c.22C>G (p.Leu8Val)	APCDD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2373647	NM_153000.5(APCDD1):c.1295G>A (p.Arg432Gln)	APCDD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3779878	NM_153000.5(APCDD1):c.1336G>A (p.Gly446Arg)	APCDD1	Uncertain significance	criteria provided, single submitter
4814025	NM_153000.5(APCDD1):c.584G>A (p.Gly195Asp)	APCDD1	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
APCDD1	Strong	Autosomal dominant	hypotrichosis 1	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
APCDD1	Orphanet:55654	Hypotrichosis simplex

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
APCDD1	HGNC:15718	ENSG00000154856	Q8J025	Protein APCDD1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
APCDD1	Protein APCDD1	Negative regulator of the Wnt signaling pathway.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
APCDD1	Other/Unknown	no		APCDD1_dom, APCDD1

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
decidua	1
nipple	1
upper arm skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
APCDD1	249	broad	marker	upper arm skin, nipple, decidua

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
APCDD1	884

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
APCDD1	Q8J025	82.10

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
regulation of odontogenesis of dentin-containing tooth	1	2407.4×	0.001	APCDD1
astrocyte cell migration	1	2407.4×	0.001	APCDD1
hair follicle development	1	383.0×	0.004	APCDD1
negative regulation of Wnt signaling pathway	1	343.9×	0.004	APCDD1
Wnt signaling pathway	1	99.7×	0.010	APCDD1

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
APCDD1	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	APCDD1

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)
APCDD1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.