Hypotrichosis 6
disease diseaseOn this page
Also known as autosomal recessive localised hypotrichosisDSG4 hypotrichosishypotrichosis caused by mutation in DSG4hypotrichosis type 6hypotrichosis, localized, autosomal recessive 1HYPT6LAH1monilethrix-like hypotrichosis
Summary
Hypotrichosis 6 (MONDO:0011932) is a disease caused by DSG4 (GenCC Definitive), with 2 cohort genes.
At a glance
- Causal gene: DSG4 (GenCC Definitive)
- Cohort genes: 2
- ClinVar variants: 116
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | hypotrichosis 6 |
| Mondo ID | MONDO:0011932 |
| MeSH | C564312 |
| OMIM | 607903 |
| DOID | DOID:0110703 |
| UMLS | C1842839 |
| MedGen | 335812 |
| GARD | 0015423 |
| Is cancer (heuristic) | no |
Also known as: autosomal recessive localised hypotrichosis · DSG4 hypotrichosis · hypotrichosis 6 · hypotrichosis caused by mutation in DSG4 · hypotrichosis type 6 · hypotrichosis, localized, autosomal recessive 1 · HYPT6 · LAH1 · Lah1 · monilethrix-like hypotrichosis
Data availability: 116 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 6
Related subtypes (18): hypotrichosis of eyelid, hypotrichosis 2, hypotrichosis 8, congenital hypotrichosis with juvenile macular dystrophy, hypotrichosis 7, hypotrichosis 1, 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
116 retrieved; paginated sample, class counts are floors:
53 uncertain significance, 25 conflicting classifications of pathogenicity, 13 benign/likely benign, 10 benign, 9 pathogenic, 6 likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 2502917 | NM_177986.5(DSG4):c.968A>G (p.Asp323Gly) | DSG1-AS1 | Pathogenic | no assertion criteria provided |
| 2502918 | NM_177986.5(DSG4):c.126_129del (p.Thr43fs) | DSG1-AS1 | Pathogenic | no assertion criteria provided |
| 2719 | NM_177986.5(DSG4):c.373-32_1005+292del | DSG1-AS1 | Pathogenic | no assertion criteria provided |
| 2724 | NM_177986.5(DSG4):c.800C>G (p.Pro267Arg) | DSG1-AS1 | Pathogenic | no assertion criteria provided |
| 4072429 | NM_177986.5(DSG4):c.624del (p.Met208fs) | DSG1-AS1 | Pathogenic | criteria provided, single submitter |
| 2721 | NM_177986.5(DSG4):c.574T>C (p.Ser192Pro) | DSG4 | Pathogenic | no assertion criteria provided |
| 2722 | NM_177986.5(DSG4):c.2038dup (p.Ser680fs) | DSG4 | Pathogenic | no assertion criteria provided |
| 2723 | NM_177986.5(DSG4):c.216+1G>T | DSG4 | Pathogenic | criteria provided, single submitter |
| 2725 | NM_177986.5(DSG4):c.763del (p.Cys255fs) | DSG4 | Pathogenic | no assertion criteria provided |
| 2720 | NM_177986.5(DSG4):c.87del (p.Lys30fs) | DSG1-AS1 | Likely pathogenic | criteria provided, single submitter |
| 2726 | NM_177986.5(DSG4):c.865C>T (p.Arg289Ter) | DSG1-AS1 | Likely pathogenic | criteria provided, single submitter |
| 4845816 | NM_177986.5(DSG4):c.1766del (p.Cys589fs) | DSG1-AS1 | Likely pathogenic | criteria provided, single submitter |
| 4845863 | NM_177986.5(DSG4):c.241C>T (p.Gln81Ter) | DSG1-AS1 | Likely pathogenic | criteria provided, single submitter |
| 3391063 | NM_177986.5(DSG4):c.2389C>T (p.Arg797Ter) | DSG4 | Likely pathogenic | criteria provided, single submitter |
| 3777044 | NM_177986.5(DSG4):c.1576T>C (p.Phe526Leu) | DSG4 | Likely pathogenic | criteria provided, single submitter |
| 326435 | NM_177986.5(DSG4):c.1480T>C (p.Cys494Arg) | DSG1-AS1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 326438 | NM_177986.5(DSG4):c.1636+12G>A | DSG1-AS1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 326440 | NM_177986.5(DSG4):c.1740A>G (p.Gln580=) | DSG1-AS1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 326443 | NM_177986.5(DSG4):c.2019C>T (p.Gly673=) | DSG1-AS1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 326453 | NM_177986.5(DSG4):c.2777A>G (p.Asp926Gly) | DSG1-AS1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 585099 | NM_177986.5(DSG4):c.1198G>A (p.Gly400Arg) | DSG1-AS1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 711703 | NM_177986.5(DSG4):c.1128T>C (p.Val376=) | DSG1-AS1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 779466 | NM_177986.5(DSG4):c.236C>T (p.Ser79Leu) | DSG1-AS1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 889353 | NM_177986.5(DSG4):c.1933+12A>G | DSG1-AS1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 889976 | NM_177986.5(DSG4):c.1278-13T>C | DSG1-AS1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 890044 | NM_177986.5(DSG4):c.2308G>A (p.Ala770Thr) | DSG1-AS1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 890046 | NM_177986.5(DSG4):c.2523G>A (p.Arg841=) | DSG1-AS1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 891786 | NM_177986.5(DSG4):c.1637-14C>T | DSG1-AS1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 891787 | NM_177986.5(DSG4):c.1655C>A (p.Thr552Lys) | DSG1-AS1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 326430 | NM_177986.5(DSG4):c.955G>A (p.Asp319Asn) | DSG4 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 5 · 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 |
|---|---|---|---|---|
| DSG4 | Definitive | Autosomal recessive | hypotrichosis 6 | 5 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| DSG4 | Orphanet:55654 | Hypotrichosis simplex |
| DSG4 | Orphanet:573 | Monilethrix |
Cohort genes → proteins
2 cohort genes, 1 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 2 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| DSG4 | HGNC:21307 | ENSG00000175065 | Q86SJ6 | Desmoglein-4 | gencc,clinvar |
| DSG1-AS1 | HGNC:51115 | ENSG00000266729 | DSG1 antisense RNA 1 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| DSG4 | Desmoglein-4 | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion. |
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) |
|---|---|---|---|---|
| DSG4 | Other/Unknown | no | Cadherin_Y-type_LIR, Cadherin-like_dom, Desmosomal_cadherin | |
| DSG1-AS1 | Other/Unknown | no |
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 |
|---|---|
| esophagus mucosa | 2 |
| male germ line stem cell (sensu Vertebrata) in testis | 2 |
| lower lobe of lung | 1 |
| lower esophagus mucosa | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| DSG4 | 24 | marker | male germ line stem cell (sensu Vertebrata) in testis, esophagus mucosa, lower lobe of lung | |
| DSG1-AS1 | 96 | tissue_specific | marker | male germ line stem cell (sensu Vertebrata) in testis, esophagus mucosa, lower esophagus mucosa |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| DSG4 | 1,636 |
| DSG1-AS1 | 0 |
Structural data
PDB: 0 · AlphaFold-only: 1 · No structure: 1
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| DSG4 | Q86SJ6 | 65.63 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 2 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× | 0.018 | DSG4 |
| Keratinization | 1 | 55.7× | 0.018 | DSG4 |
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 |
|---|---|---|---|---|
| hair follicle development | 1 | 383.0× | 0.008 | DSG4 |
| keratinocyte differentiation | 1 | 247.8× | 0.008 | DSG4 |
| BMP signaling pathway | 1 | 200.6× | 0.008 | DSG4 |
| homophilic cell-cell adhesion | 1 | 140.4× | 0.009 | DSG4 |
| cell-cell adhesion | 1 | 101.5× | 0.010 | DSG4 |
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 |
|---|---|---|
| DSG4 | 0 | 0 |
| DSG1-AS1 | 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 | 2 | DSG4, DSG1-AS1 |
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) |
|---|---|---|
| DSG4 | 0 | — |
| DSG1-AS1 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.