Congenital hypotrichosis with juvenile macular dystrophy

Summary

Congenital hypotrichosis with juvenile macular dystrophy (MONDO:0011107) is a disease caused by CDH3 (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: CDH3 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 25
• Phenotypes (HPO): 15

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		50	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

15 HPO clinical features (Orphanet curated; top 15 by frequency):

HPO ID	Term	Frequency
HP:0000608	Macular degeneration	Very frequent (80-99%)
HP:0000618	Blindness	Very frequent (80-99%)
HP:0002209	Sparse scalp hair	Very frequent (80-99%)
HP:0004322	Short stature	Very frequent (80-99%)
HP:0008002	Abnormality of macular pigmentation	Very frequent (80-99%)
HP:0002213	Fine hair	Frequent (30-79%)
HP:0002299	Brittle hair	Frequent (30-79%)
HP:0003777	Pili torti	Frequent (30-79%)
HP:0000639	Nystagmus	Occasional (5-29%)
HP:0000962	Hyperkeratosis	Occasional (5-29%)
HP:0000995	Melanocytic nevus	Occasional (5-29%)
HP:0001480	Freckling	Occasional (5-29%)
HP:0002652	Skeletal dysplasia	Occasional (5-29%)
HP:0002813	Abnormality of limb bone morphology	Occasional (5-29%)
HP:0100326	Immunologic hypersensitivity	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital hypotrichosis with juvenile macular dystrophy
Mondo ID	MONDO:0011107
MeSH	C537698
OMIM	601553
Orphanet	1573
DOID	DOID:0110711
UMLS	C1832162
MedGen	316921
GARD	0003066
Is cancer (heuristic)	no

Also known as: HJMD · Hjmd · hypotrichosis with cone-rod dystrophy · hypotrichosis with juvenile macular dystrophy · hypotrichosis, congenital, with juvenile macular dystrophy · juvenile macular degeneration and hypotrichosis · juvenile macular dystrophy and congenital hypotrichosis

Data availability: 25 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 › congenital hypotrichosis with juvenile macular dystrophy

Related subtypes (18): hypotrichosis of eyelid, hypotrichosis 2, hypotrichosis 8, 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

25 retrieved; paginated sample, class counts are floors:

9 benign, 8 pathogenic, 3 uncertain significance, 3 likely pathogenic, 1 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1322049	NM_001793.6(CDH3):c.160+1G>A	CDH3	Pathogenic	criteria provided, multiple submitters, no conflicts
1454138	NM_001793.6(CDH3):c.661C>T (p.Arg221Ter)	CDH3	Pathogenic	criteria provided, multiple submitters, no conflicts
1459147	NM_001793.6(CDH3):c.1086G>A (p.Trp362Ter)	CDH3	Pathogenic	criteria provided, multiple submitters, no conflicts
17638	NM_001793.6(CDH3):c.981del (p.Met327fs)	CDH3	Pathogenic	no assertion criteria provided
17639	NM_001793.6(CDH3):c.1508G>A (p.Arg503His)	CDH3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
17641	NM_001793.6(CDH3):c.830del (p.Gly277fs)	CDH3	Pathogenic	criteria provided, multiple submitters, no conflicts
3779500	NM_001793.6(CDH3):c.2158C>T (p.Arg720Ter)	CDH3	Pathogenic	criteria provided, single submitter
666275	NM_001793.6(CDH3):c.1795+1G>C	CDH3	Pathogenic	no assertion criteria provided
866071	NM_001793.6(CDH3):c.307C>T (p.Arg103Ter)	CDH3	Pathogenic	criteria provided, multiple submitters, no conflicts
3779499	NM_001793.6(CDH3):c.2122G>T (p.Glu708Ter)	CDH3	Likely pathogenic	criteria provided, single submitter
666276	NM_001793.6(CDH3):c.1063G>T (p.Asp355Tyr)	CDH3	Likely pathogenic	criteria provided, single submitter
800872	NM_001793.6(CDH3):c.1918T>G (p.Cys640Gly)	CDH3	Likely pathogenic	no assertion criteria provided
884849	NM_001793.6(CDH3):c.1808T>C (p.Val603Ala)	CDH3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1054147	NM_001793.6(CDH3):c.1199C>G (p.Ala400Gly)	CDH3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1402815	NM_001793.6(CDH3):c.475G>A (p.Ala159Thr)	CDH3	Uncertain significance	criteria provided, multiple submitters, no conflicts
2442156	NM_001793.6(CDH3):c.958G>A (p.Asp320Asn)	CDH3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1192667	NM_001793.6(CDH3):c.160+117G>A	CDH3	Benign	criteria provided, multiple submitters, no conflicts
1192714	NM_001793.6(CDH3):c.2281-45A>C	CDH3	Benign	criteria provided, multiple submitters, no conflicts
320229	NM_001793.6(CDH3):c.720G>A (p.Thr240=)	CDH3	Benign	criteria provided, multiple submitters, no conflicts
320230	NM_001793.6(CDH3):c.813C>A (p.Thr271=)	CDH3	Benign	criteria provided, multiple submitters, no conflicts
320243	NM_001793.6(CDH3):c.1626T>C (p.Asn542=)	CDH3	Benign	criteria provided, multiple submitters, no conflicts
320250	NM_001793.6(CDH3):c.1956G>A (p.Lys652=)	CDH3	Benign	criteria provided, multiple submitters, no conflicts
677162	NM_001793.6(CDH3):c.390+37T>C	CDH3	Benign	criteria provided, multiple submitters, no conflicts
677217	NM_001793.6(CDH3):c.247-38A>G	CDH3	Benign	criteria provided, multiple submitters, no conflicts
93783	NM_001793.6(CDH3):c.2239C>A (p.Arg747=)	CDH3	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · 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
CDH3	Strong	Autosomal recessive	congenital hypotrichosis with juvenile macular dystrophy	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CDH3	Orphanet:1573	Hypotrichosis with juvenile macular degeneration
CDH3	Orphanet:1897	EEM syndrome

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
CDH3	HGNC:1762	ENSG00000062038	P22223	Cadherin-3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CDH3	Cadherin-3	Cadherins are calcium-dependent cell adhesion proteins.

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)
CDH3	Other/Unknown	no		Cadherin_Y-type_LIR, Cadherin-like_dom, Cadherin_pro_dom

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
mammary duct	1
oocyte	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CDH3	213	tissue_specific	marker	secondary oocyte, oocyte, mammary duct

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CDH3	1,749

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CDH3	P22223	19

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
Adherens junctions interactions	1	248.3×	0.007	CDH3
Cell-cell junction organization	1	248.3×	0.007	CDH3
Cell junction organization	1	187.2×	0.007	CDH3
Cell-Cell communication	1	137.6×	0.007	CDH3

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 timing of catagen	1	16852.0×	0.001	CDH3
regulation of transport	1	8426.0×	0.001	CDH3
hair cycle process	1	2808.7×	0.002	CDH3
hair follicle maturation	1	2106.5×	0.002	CDH3
positive regulation of melanin biosynthetic process	1	1404.3×	0.003	CDH3
positive regulation of insulin-like growth factor receptor signaling pathway	1	1203.7×	0.003	CDH3
retina homeostasis	1	1123.5×	0.003	CDH3
positive regulation of keratinocyte proliferation	1	991.3×	0.003	CDH3
adherens junction organization	1	510.7×	0.004	CDH3
calcium-dependent cell-cell adhesion	1	481.5×	0.004	CDH3
cell-cell junction assembly	1	443.5×	0.004	CDH3
cell-cell adhesion mediated by cadherin	1	411.0×	0.004	CDH3
keratinization	1	234.1×	0.007	CDH3
negative regulation of transforming growth factor beta receptor signaling pathway	1	173.7×	0.008	CDH3
cell morphogenesis	1	157.5×	0.008	CDH3
positive regulation of canonical Wnt signaling pathway	1	154.6×	0.008	CDH3
homophilic cell-cell adhesion	1	140.4×	0.008	CDH3
visual perception	1	79.5×	0.014	CDH3
cell migration	1	61.5×	0.017	CDH3
cell adhesion	1	37.5×	0.027	CDH3

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 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
CDH3	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	CDH3

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)
CDH3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.