Hypotrichosis 2

Summary

Hypotrichosis 2 (MONDO:0007805) is a disease caused by CDSN (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: CDSN (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hypotrichosis 2
Mondo ID	MONDO:0007805
MeSH	C564143
OMIM	146520
DOID	DOID:0110699
UMLS	C1840299
MedGen	374435
GARD	0018093
Is cancer (heuristic)	no

Also known as: CDSN hypotrichosis · hypotrichosis 2 · hypotrichosis caused by mutation in CDSN · hypotrichosis simplex of the scalp 1 · hypotrichosis type 2 · HYPT2 · hypt2

Data availability: 5 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 2

Related subtypes (18): hypotrichosis of eyelid, 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, 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

5 retrieved; paginated sample, class counts are floors:

2 pathogenic, 1 uncertain significance, 1 benign/likely benign, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
6997	NM_001264.5(CDSN):c.643C>T (p.Gln215Ter)	CDSN	Pathogenic	no assertion criteria provided
6998	NM_001264.5(CDSN):c.598C>T (p.Gln200Ter)	CDSN	Pathogenic	no assertion criteria provided
1027849	NM_001264.5(CDSN):c.1340C>T (p.Pro447Leu)	CDSN	Uncertain significance	criteria provided, multiple submitters, no conflicts
716000	NM_001264.5(CDSN):c.1525C>T (p.Leu509=)	CDSN	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
716865	NM_001264.5(CDSN):c.536A>G (p.Asn179Ser)	CDSN	Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 2 · 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
CDSN	Strong	Autosomal dominant	hypotrichosis 2	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CDSN	Orphanet:263553	Peeling skin syndrome type B
CDSN	Orphanet:90368	Hypotrichosis simplex of the scalp

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
CDSN	HGNC:1802	ENSG00000204539	Q15517	Corneodesmosin	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CDSN	Corneodesmosin	Important for the epidermal barrier integrity.

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)
CDSN	Other/Unknown	no		Corneodesmosin

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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
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
CDSN	101	tissue_specific	yes	skin of abdomen, zone of skin, skin of leg

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CDSN	1,223

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CDSN	Q15517	38.13

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 1 evidence-associated genes (1 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 1 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	1	87.8×	0.027	CDSN
Keratinization	1	55.7×	0.027	CDSN
Developmental Biology	1	14.5×	0.069	CDSN

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
negative regulation of cornification	1	16852.0×	5e-04	CDSN
corneocyte desquamation	1	8426.0×	5e-04	CDSN
skin morphogenesis	1	1404.3×	0.002	CDSN
amyloid fibril formation	1	601.9×	0.003	CDSN
keratinocyte differentiation	1	247.8×	0.006	CDSN
epidermis development	1	210.7×	0.006	CDSN
cell-cell adhesion	1	101.5×	0.011	CDSN
cell adhesion	1	37.5×	0.027	CDSN

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
CDSN	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	CDSN

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)
CDSN	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.