Dyschromatosis universalis hereditaria 1

Summary

Dyschromatosis universalis hereditaria 1 (MONDO:0024524) is a disease caused by SASH1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: SASH1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 23

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	dyschromatosis universalis hereditaria 1
Mondo ID	MONDO:0024524
MeSH	C567273
OMIM	127500
UMLS	C2675711
MedGen	390864
GARD	0025411
Is cancer (heuristic)	no

Also known as: DUH1 · dyschromatosis universalis hereditaria 1

Data availability: 23 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › skin disorder › skin pigmentation disorder › hyperpigmentation of the skin › dyschromatosis universalis hereditaria › dyschromatosis universalis hereditaria 1

Related subtypes (2): dyschromatosis universalis hereditaria 2, dyschromatosis universalis hereditaria 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

ClinVar germline variants

23 retrieved; paginated sample, class counts are floors:

11 likely pathogenic, 6 uncertain significance, 3 benign, 2 benign/likely benign, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
624631	NM_015278.5(SASH1):c.1527_1530dup (p.Leu511fs)	SASH1	Pathogenic	no assertion criteria provided
2430242	NM_015278.5(SASH1):c.1548T>A (p.Ser516Arg)	SASH1	Likely pathogenic	criteria provided, single submitter
2430283	NM_015278.5(SASH1):c.1811C>A (p.Thr604Lys)	SASH1	Likely pathogenic	criteria provided, single submitter
2444026	NM_015278.5(SASH1):c.1574C>T (p.Thr525Ile)	SASH1	Likely pathogenic	criteria provided, single submitter
3775235	NM_015278.5(SASH1):c.1546A>C (p.Ser516Arg)	SASH1	Likely pathogenic	criteria provided, single submitter
3776092	NM_015278.5(SASH1):c.1930C>T (p.Arg644Trp)	SASH1	Likely pathogenic	criteria provided, single submitter
624625	NM_015278.5(SASH1):c.1651T>G (p.Tyr551Asp)	SASH1	Likely pathogenic	criteria provided, single submitter
624626	NM_015278.5(SASH1):c.1544T>C (p.Leu515Pro)	SASH1	Likely pathogenic	criteria provided, single submitter
624627	NM_015278.5(SASH1):c.1525G>A (p.Glu509Lys)	SASH1	Likely pathogenic	criteria provided, single submitter
624629	NM_015278.5(SASH1):c.1556G>A (p.Ser519Asn)	SASH1	Likely pathogenic	criteria provided, single submitter
624632	NM_015278.5(SASH1):c.1519T>G (p.Ser507Ala)	SASH1	Likely pathogenic	criteria provided, single submitter
624633	NM_015278.5(SASH1):c.1651T>C (p.Tyr551His)	SASH1	Likely pathogenic	criteria provided, single submitter
1048561	NM_015278.5(SASH1):c.1529G>A (p.Ser510Asn)	SASH1	Uncertain significance	criteria provided, single submitter
3593216	NM_015278.5(SASH1):c.3391G>T (p.Ala1131Ser)	SASH1	Uncertain significance	criteria provided, single submitter
3892352	NM_015278.5(SASH1):c.1931G>A (p.Arg644Gln)	SASH1	Uncertain significance	criteria provided, single submitter
3892353	NM_015278.5(SASH1):c.2095+14_2095+145del	SASH1	Uncertain significance	criteria provided, single submitter
624630	NM_015278.5(SASH1):c.1537A>C (p.Ser513Arg)	SASH1	Uncertain significance	criteria provided, single submitter
624634	NM_015278.5(SASH1):c.1784T>C (p.Met595Thr)	SASH1	Uncertain significance	criteria provided, single submitter
1257635	NM_015278.5(SASH1):c.2651A>G (p.Gln884Arg)	SASH1	Benign	criteria provided, multiple submitters, no conflicts
1289486	NM_015278.5(SASH1):c.337-38G>C	SASH1	Benign	criteria provided, multiple submitters, no conflicts
1290003	NM_015278.5(SASH1):c.45CGAGCC[3] (p.12EP[7])	SASH1	Benign	criteria provided, multiple submitters, no conflicts
783757	NM_015278.5(SASH1):c.3266G>A (p.Arg1089Gln)	SASH1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
789886	NM_015278.5(SASH1):c.2459G>A (p.Arg820Gln)	SASH1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
SASH1	Strong	Autosomal dominant	dyschromatosis universalis hereditaria 1	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SASH1	Orphanet:231040	Familial generalized lentiginosis
SASH1	Orphanet:447961	Pigmentation defects-palmoplantar keratoderma-skin carcinoma 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
SASH1	HGNC:19182	ENSG00000111961	O94885	SAM and SH3 domain-containing protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SASH1	SAM and SH3 domain-containing protein 1	Is a positive regulator of NF-kappa-B signaling downstream of TLR4 activation.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SASH1	Transcription factor	no		SH3_domain, SAM, SAM/pointed_sf

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
lateral globus pallidus	1
skin of hip	1
synovial joint	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SASH1	293	ubiquitous	marker	synovial joint, lateral globus pallidus, skin of hip

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SASH1	879

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SASH1	O94885	2

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 protein K63-linked ubiquitination	1	16852.0×	3e-04	SASH1
regulation of protein autoubiquitination	1	16852.0×	3e-04	SASH1
regulation of epithelial cell migration	1	2808.7×	0.001	SASH1
positive regulation of lipopolysaccharide-mediated signaling pathway	1	1532.0×	0.002	SASH1
positive regulation of JUN kinase activity	1	1296.3×	0.002	SASH1
positive regulation of p38MAPK cascade	1	624.1×	0.003	SASH1
positive regulation of non-canonical NF-kappaB signal transduction	1	255.3×	0.005	SASH1
positive regulation of endothelial cell migration	1	251.5×	0.005	SASH1
protein polyubiquitination	1	115.4×	0.009	SASH1
positive regulation of angiogenesis	1	115.4×	0.009	SASH1

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
SASH1	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	SASH1

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)
SASH1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.