Olmsted syndrome 1

Summary

Olmsted syndrome 1 (MONDO:0100296) is a disease caused by TRPV3 (GenCC Strong), with 1 cohort gene and 1 clinical trial.

At a glance

• Causal gene: TRPV3 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 21
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Olmsted syndrome 1
Mondo ID	MONDO:0100296
OMIM	614594
DOID	DOID:0112013
UMLS	C5542829
MedGen	1778121
GARD	0015818
Is cancer (heuristic)	no

Also known as: Olmsted syndrome · palmoplantar keratoderma, mutilating, with periorificial keratotic plaques 1

Data availability: 21 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › skin disorder › keratosis › palmoplantar keratosis › hereditary palmoplantar keratoderma › Olmsted syndrome › Olmsted syndrome 1

Related subtypes (2): Olmsted syndrome, X-linked, Olmsted syndrome 2

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

21 retrieved; paginated sample, class counts are floors:

9 benign, 5 uncertain significance, 4 pathogenic, 2 benign/likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
192256	NM_145068.4(TRPV3):c.2017C>T (p.Leu673Phe)	TRPV3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
30636	NM_145068.4(TRPV3):c.1717G>A (p.Gly573Ser)	TRPV3	Pathogenic	criteria provided, single submitter
30637	NM_145068.4(TRPV3):c.1717G>T (p.Gly573Cys)	TRPV3	Pathogenic	no assertion criteria provided
30638	NM_145068.4(TRPV3):c.2074T>G (p.Trp692Gly)	TRPV3	Pathogenic	no assertion criteria provided
803297	NM_145068.4(TRPV3):c.1703G>T (p.Gly568Val)	TRPV3	Pathogenic	criteria provided, single submitter
225504	NM_145068.4(TRPV3):c.881C>A (p.Ser294Ter)	TRPV3	Uncertain significance	criteria provided, single submitter
2282884	NM_145068.4(TRPV3):c.1251T>G (p.His417Gln)	TRPV3	Uncertain significance	criteria provided, multiple submitters, no conflicts
3581860	NM_145068.4(TRPV3):c.1910T>C (p.Ile637Thr)	TRPV3	Uncertain significance	criteria provided, single submitter
3811155	NM_145068.4(TRPV3):c.2068C>T (p.Arg690Cys)	TRPV3	Uncertain significance	criteria provided, multiple submitters, no conflicts
3892735	NM_145068.4(TRPV3):c.764A>G (p.Gln255Arg)	TRPV3	Uncertain significance	criteria provided, single submitter
1259700	NM_145068.4(TRPV3):c.1065+16G>T	TRPV3	Benign	criteria provided, multiple submitters, no conflicts
1262763	NM_145068.4(TRPV3):c.1066-46T>C	TRPV3	Benign	criteria provided, multiple submitters, no conflicts
1283223	NM_145068.4(TRPV3):c.224+27T>C	TRPV3	Benign	criteria provided, multiple submitters, no conflicts
322753	NM_145068.4(TRPV3):c.2321C>T (p.Thr774Ile)	TRPV3	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
322758	NM_145068.4(TRPV3):c.1923C>T (p.Asp641=)	TRPV3	Benign	criteria provided, multiple submitters, no conflicts
322784	NM_145068.4(TRPV3):c.936G>A (p.Thr312=)	TRPV3	Benign	criteria provided, multiple submitters, no conflicts
322788	NM_145068.4(TRPV3):c.558A>C (p.Ile186=)	TRPV3	Benign	criteria provided, multiple submitters, no conflicts
322794	NM_145068.4(TRPV3):c.349A>G (p.Arg117Gly)	TRPV3	Benign	criteria provided, multiple submitters, no conflicts
322795	NM_145068.4(TRPV3):c.270G>A (p.Gln90=)	TRPV3	Benign	criteria provided, multiple submitters, no conflicts
322796	NM_145068.4(TRPV3):c.224+8C>T	TRPV3	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
322799	NM_145068.4(TRPV3):c.73A>G (p.Ile25Val)	TRPV3	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
TRPV3	Strong	Autosomal dominant	Olmsted syndrome 1	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TRPV3	Orphanet:448264	Isolated focal non-epidermolytic palmoplantar keratoderma
TRPV3	Orphanet:659	Mutilating palmoplantar keratoderma with periorificial keratotic plaques

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
TRPV3	HGNC:18084	ENSG00000167723	Q8NET8	Transient receptor potential cation channel subfamily V member 3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TRPV3	Transient receptor potential cation channel subfamily V member 3	Non-selective calcium permeant cation channel.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Ion channel	1	111.5×	0.009

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TRPV3	Ion channel	yes		Ankyrin_rpt, Ion_trans_dom, TrpV1-4

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
skin of abdomen	1
skin of leg	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TRPV3	157	broad	marker	skin of leg, skin of abdomen, sural nerve

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TRPV3	931

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TRPV3	Q8NET8	34

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
TRP channels	1	407.9×	0.002	TRPV3

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 hair cycle	1	16852.0×	4e-04	TRPV3
osmosensory signaling pathway	1	1532.0×	0.002	TRPV3
response to temperature stimulus	1	1532.0×	0.002	TRPV3
positive regulation of calcium ion import	1	936.2×	0.002	TRPV3
calcium ion import across plasma membrane	1	543.6×	0.003	TRPV3
calcium ion transmembrane transport	1	210.7×	0.006	TRPV3
actin filament organization	1	118.7×	0.008	TRPV3

Therapeutics

Drug target analysis

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

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
TRPV3	4	3

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CANNABINOL	3	TRPV3
TETRAHYDROCANNABIVARIN	2	TRPV3
CANNABIDIVARIN	2	TRPV3
CANNABIGEROL	2	TRPV3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
TRPV3	55	Binding:52, Functional:3

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

4 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.

Compound	Max phase	Cohort target (bioactivity)
CANNABINOL	3	TRPV3
TETRAHYDROCANNABIVARIN	2	TRPV3
CANNABIDIVARIN	2	TRPV3
CANNABIGEROL	2	TRPV3

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	1	TRPV3
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07090889	PHASE1	RECRUITING	Study of KM-023 in Healthy Volunteers and Patients With Olmsted Syndrome.