Hypotrichosis simplex of the scalp

Summary

Hypotrichosis simplex of the scalp (MONDO:0019575) is a disease with 2 cohort genes.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 2
• Phenotypes (HPO): 21

Clinical features

Signs & symptoms

Clinical features (HPO)

21 HPO clinical features (Orphanet curated; top 21 by frequency):

HPO ID	Term	Frequency
HP:0002213	Fine hair	Very frequent (80-99%)
HP:0100038	Slow-growing scalp hair	Very frequent (80-99%)
HP:0000962	Hyperkeratosis	Frequent (30-79%)
HP:0001036	Parakeratosis	Frequent (30-79%)
HP:0002209	Sparse scalp hair	Frequent (30-79%)
HP:0002293	Alopecia of scalp	Frequent (30-79%)
HP:0025092	Epidermal acanthosis	Frequent (30-79%)
HP:0000989	Pruritus	Occasional (5-29%)
HP:0001047	Atopic dermatitis	Occasional (5-29%)
HP:0003193	Allergic rhinitis	Occasional (5-29%)
HP:0003212	Increased circulating IgE level	Occasional (5-29%)
HP:0040189	Scaling skin	Occasional (5-29%)
HP:0000164	Abnormality of the dentition	Excluded (0%)
HP:0000499	Abnormal eyelash morphology	Excluded (0%)
HP:0000534	Abnormal eyebrow morphology	Excluded (0%)
HP:0001597	Abnormality of the nail	Excluded (0%)
HP:0002550	Absent facial hair	Excluded (0%)
HP:0004528	Generalized hypotrichosis	Excluded (0%)
HP:0007550	Hypohidrosis or hyperhidrosis	Excluded (0%)
HP:0100133	Abnormality of the pubic hair	Excluded (0%)
HP:0100134	Abnormality of the axillary hair	Excluded (0%)

Identifiers

Disease identifiers

Field	Value
Canonical name	hypotrichosis simplex of the scalp
Mondo ID	MONDO:0019575
Orphanet	90368
SNOMED CT	717256009
GARD	0016789
Is cancer (heuristic)	no

Also known as: hereditary hypotrichosis simplex of the scalp

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 › hair anomaly › alopecia › hypotrichosis simplex of the scalp

Related subtypes (25): alopecia, isolated, telogen effluvium, alopecia areata, chemotherapy-induced alopecia, alopecia mucinosa, atrichia with papular lesions, loose anagen syndrome, Satoyoshi syndrome, alopecia-intellectual disability-hypergonadotropic hypogonadism syndrome, hereditary hypotrichosis with recurrent skin vesicles, alopecia antibody deficiency, pseudopelade of Brocq, frontal fibrosing alopecia, Quinquaud’s folliculitis decalvans, Graham Little-Piccardi-Lassueur syndrome, lichen planopilaris, hypotrichosis simplex, alopecia totalis, endocrine alopecia, alopecia universalis onychodystrophy vitiligo, central centrifugal cicatricial alopecia, ectodermal dysplasia alopecia preaxial polydactyly, Slti-Salem syndrome, microcephaly sparse hair intellectual disability seizures, alopecia universalis

Subtypes (2): hypotrichosis 2, hypotrichosis 3

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: 15 · Orphanet: 5 · 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
KRT74	Moderate	Autosomal dominant	hypotrichosis 3	8

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
KRT74	Orphanet:170	Woolly hair
KRT74	Orphanet:69084	Pure hair and nail ectodermal dysplasia
KRT74	Orphanet:90368	Hypotrichosis simplex of the scalp

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
CDSN	HGNC:1802	ENSG00000204539	Q15517	Corneodesmosin	gencc
KRT74	HGNC:28929	ENSG00000170484	Q7RTS7	Keratin, type II cytoskeletal 74	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CDSN	Corneodesmosin	Important for the epidermal barrier integrity.
KRT74	Keratin, type II cytoskeletal 74	Has a role in hair formation.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CDSN	Other/Unknown	no		Corneodesmosin
KRT74	Other/Unknown	no		Keratin_II, IF_conserved, Keratin_2_head

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
skin of abdomen	1
skin of leg	1
zone of skin	1
male germ line stem cell (sensu Vertebrata) in testis	1
tibialis anterior	1
upper arm 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
KRT74	40	tissue_specific	yes	upper arm skin, male germ line stem cell (sensu Vertebrata) in testis, tibialis anterior

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CDSN	1,223
KRT74	451

Intra-cohort edges

A	B	Sources
CDSN	KRT74	string_interaction

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
KRT74	Q7RTS7	72.11
CDSN	Q15517	38.13

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Formation of the cornified envelope	2	87.8×	4e-04	CDSN, KRT74
Keratinization	2	55.7×	5e-04	CDSN, KRT74
Developmental Biology	2	14.5×	0.005	CDSN, KRT74

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
negative regulation of cornification	1	8426.0×	0.001	CDSN
corneocyte desquamation	1	4213.0×	0.001	CDSN
skin morphogenesis	1	702.2×	0.005	CDSN
intermediate filament cytoskeleton organization	1	468.1×	0.006	KRT74
amyloid fibril formation	1	300.9×	0.007	CDSN
keratinocyte differentiation	1	123.9×	0.012	CDSN
intermediate filament organization	1	120.4×	0.012	KRT74
keratinization	1	117.0×	0.012	KRT74
epidermis development	1	105.3×	0.012	CDSN
cell-cell adhesion	1	50.8×	0.022	CDSN
cell adhesion	1	18.7×	0.053	CDSN

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
CDSN	0	0
KRT74	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
E	Difficult family or no structure, no drug	2	CDSN, KRT74

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)
CDSN	0	—
KRT74	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.