Familial generalized lentiginosis

Summary

Familial generalized lentiginosis (MONDO:0007891) is a disease with 1 cohort gene.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	familial generalized lentiginosis
Mondo ID	MONDO:0007891
MeSH	C573023
OMIM	151001
Orphanet	231040
SNOMED CT	765195000
UMLS	C3492944
MedGen	486897
GARD	0017158
Is cancer (heuristic)	no

Also known as: familial lentigines profusa · familial multiple lentigines syndrome without systemic involvement · lentiginosis, generalised

Data availability: 1 GenCC gene-disease record.

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 › familial generalized lentiginosis

Related subtypes (23): dyschromatosis universalis hereditaria, cafe au lait spots, multiple, dermatopathia pigmentosa reticularis, dyschromatosis symmetrica hereditaria, extrasystoles-short stature-hyperpigmentation-microcephaly syndrome, gastrocutaneous syndrome, hyperkeratosis-hyperpigmentation syndrome, Naegeli-Franceschetti-Jadassohn syndrome, schwannomatosis, Dowling-Degos disease, H syndrome, Legius syndrome, familial progressive hyperpigmentation, linear and whorled nevoid hypermelanosis, reticulate acropigmentation of Kitamura, nail and teeth abnormalities-marginal palmoplantar keratoderma-oral hyperpigmentation syndrome, severe growth deficiency-strabismus-extensive dermal melanocytosis-intellectual disability syndrome, leukonychia totalis-acanthosis-nigricans-like lesions-abnormal hair syndrome, osteopathia striata-pigmentary dermopathy-white forelock syndrome, phakomatosis pigmentovascularis, acromelanosis, hyperpigmentation, progressive cribriform and zosteriform, mosaic Legius syndrome

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: 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	Supportive	Autosomal dominant	familial generalized lentiginosis	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

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.