Amyloidosis, primary localized cutaneous, 1

Summary

Amyloidosis, primary localized cutaneous, 1 (MONDO:0024522) is a disease caused by OSMR (GenCC Strong), with 1 cohort gene and 7 clinical trials. Top therapeutic interventions include gallium ga 68 gozetotide.

At a glance

• Causal gene: OSMR (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 11
• Clinical trials: 7

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	amyloidosis, primary localized cutaneous, 1
Mondo ID	MONDO:0024522
OMIM	105250
DOID	DOID:0080930
UMLS	C4551501
MedGen	1639046
GARD	0018637
Is cancer (heuristic)	no

Also known as: amyloidosis 9 · amyloidosis, primary cutaneous, 1 · amyloidosis, primary localised cutaneous, type 1 · amyloidosis, primary localized cutaneous, 1 · amyloidosis, primary localized cutaneous, type 1 · OSMR primary cutaneous amyloidosis · PCA · PLCA1 · primary cutaneous amyloidosis caused by mutation in OSMR

Data availability: 11 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › proteostasis deficiencies › amyloidosis › primary cutaneous amyloidosis › familial primary localized cutaneous amyloidosis › amyloidosis, primary localized cutaneous, 1

Related subtypes (2): amyloidosis, primary localized cutaneous, 2, amyloidosis, primary localized cutaneous, 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

11 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
30220	NM_003999.3(OSMR):c.1940A>T (p.Asp647Val)	OSMR	Pathogenic	no assertion criteria provided
30221	NM_003999.3(OSMR):c.2081C>T (p.Pro694Leu)	OSMR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
30222	NM_003999.3(OSMR):c.2090A>C (p.Lys697Thr)	OSMR	Pathogenic	no assertion criteria provided
7809	NM_003999.3(OSMR):c.1853G>C (p.Gly618Ala)	OSMR	Pathogenic	no assertion criteria provided
7808	NM_003999.3(OSMR):c.2072T>C (p.Ile691Thr)	OSMR	Likely pathogenic	criteria provided, single submitter
802119	NM_003999.3(OSMR):c.1538G>A (p.Gly513Asp)	OSMR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3383184	NM_003999.3(OSMR):c.1786C>T (p.Arg596Ter)	OSMR	Uncertain significance	criteria provided, single submitter
3891883	NM_003999.3(OSMR):c.1985T>C (p.Val662Ala)	OSMR	Uncertain significance	criteria provided, multiple submitters, no conflicts
3891884	NM_003999.3(OSMR):c.572T>C (p.Leu191Pro)	OSMR	Uncertain significance	criteria provided, single submitter
4277702	NM_003999.3(OSMR):c.2209_2212dup (p.Ser739fs)	OSMR	Uncertain significance	criteria provided, single submitter
4686619	NM_003999.3(OSMR):c.2536A>T (p.Asn846Tyr)	OSMR	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · 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
OSMR	Strong	Autosomal dominant	amyloidosis, primary localized cutaneous, 1	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
OSMR	Orphanet:353220	Familial primary localized cutaneous amyloidosis

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
OSMR	HGNC:8507	ENSG00000145623	Q99650	Oncostatin-M-specific receptor subunit beta	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
OSMR	Oncostatin-M-specific receptor subunit beta	Associates with IL31RA to form the IL31 receptor.

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
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
OSMR	Antibody/Immunoglobulin	yes		Hematopoietin_rcpt_Gp130_CS, FN3_dom, Ig-like_fold

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
cartilage tissue	1
pericardium	1
saphenous vein	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
OSMR	256	ubiquitous	marker	pericardium, saphenous vein, cartilage tissue

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
OSMR	1,636

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
OSMR	Q99650	74.07

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
IL-6-type cytokine receptor ligand interactions	1	634.4×	0.002	OSMR

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
oncostatin-M-mediated signaling pathway	1	4213.0×	0.001	OSMR
positive regulation of acute inflammatory response	1	1404.3×	0.002	OSMR
response to cytokine	1	374.5×	0.004	OSMR
cytokine-mediated signaling pathway	1	130.6×	0.010	OSMR
positive regulation of cell population proliferation	1	33.6×	0.030	OSMR

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
OSMR	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	1	OSMR
E	Difficult family or no structure, no drug	0

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)
OSMR	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 7.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	6
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07052214	PHASE3	RECRUITING	PSMA PET Combined With MRI for the Detection of PCa
NCT04680130	Not specified	ENROLLING_BY_INVITATION	Clinico-Pathologic-Genetic-Imaging Study of Neurodegenerative and Related Disorders
NCT06820190	Not specified	RECRUITING	Analgesic Efficacy of Multiple Mid-Transverse Process to Pleura (MTP) Block and PCA in Idiopathic Scoliosis Patients Undergoing Posterior Spinal Fusion
NCT07051109	Not specified	RECRUITING	Dual-chamber Patient-controlled Analgesia for Postoperative Recovery
NCT04929054	Not specified	UNKNOWN	PCR Based CEUS in BI RADS 4A Nodules
NCT05688371	Not specified	UNKNOWN	Dexmedetomidine Plus Low Dose Morphine Versus Standard Dose of Morphine in PCA in Children .
NCT05845281	Not specified	COMPLETED	Comparison of Erector Spinae Plane Block and Intravenous Patient-controlled Analgesia in Percutaneous Nephrolithotomy

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
GALLIUM GA 68 GOZETOTIDE	4	1
CHEMBL4589226	0	1