Familial primary localized cutaneous amyloidosis

Summary

Familial primary localized cutaneous amyloidosis (MONDO:0007101) is a disease with 2 cohort genes and 1 clinical trial.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 2
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	familial primary localized cutaneous amyloidosis
Mondo ID	MONDO:0007101
MeSH	C562643
OMIM	105250
Orphanet	353220
UMLS	C1304242
MedGen	725603
GARD	0017533
Is cancer (heuristic)	no

Also known as: FPLCA · hereditary primary cutaneous amyloidosis · primary localised cutaneous amyloidosis · primary localized cutaneous amyloidosis

Data availability: 2 GenCC gene-disease records · 1 cell line.

Disease family

An umbrella term covering 3 Mondo subtypes.

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

Related subtypes (4): nodular cutaneous amyloidosis, macular amyloidosis, amyloidosis cutis dyschromia, lichen amyloidosis

Subtypes (3): amyloidosis, primary localized cutaneous, 2, amyloidosis, primary localized cutaneous, 1, 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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · 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
OSMR	Strong	Autosomal dominant	amyloidosis, primary localized cutaneous, 1	5
IL31RA	Supportive	Autosomal dominant	familial primary localized cutaneous amyloidosis	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
IL31RA	Orphanet:353220	Familial primary localized cutaneous amyloidosis
OSMR	Orphanet:353220	Familial primary localized cutaneous amyloidosis

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
IL31RA	HGNC:18969	ENSG00000164509	Q8NI17	Interleukin-31 receptor subunit alpha	gencc
OSMR	HGNC:8507	ENSG00000145623	Q99650	Oncostatin-M-specific receptor subunit beta	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IL31RA	Interleukin-31 receptor subunit alpha	Associates with OSMR to form the interleukin-31 receptor which activates STAT3 and to a lower extent STAT1 and STAT5.
OSMR	Oncostatin-M-specific receptor subunit beta	Associates with IL31RA to form the IL31 receptor.

Protein-family classification

Druggable: 2 · 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	2	29.2×	0.001

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
IL31RA	Antibody/Immunoglobulin	yes		FN3_dom, Ig-like_fold, TypeI_recpt_CBD
OSMR	Antibody/Immunoglobulin	yes		Hematopoietin_rcpt_Gp130_CS, FN3_dom, Ig-like_fold

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
male germ line stem cell (sensu Vertebrata) in testis	1
monocyte	1
primordial germ cell in gonad	1
cartilage tissue	1
pericardium	1
saphenous vein	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IL31RA	129	broad	marker	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, monocyte
OSMR	256	ubiquitous	marker	pericardium, saphenous vein, cartilage tissue

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IL31RA	2,789
OSMR	1,636

Intra-cohort edges

A	B	Sources
IL31RA	OSMR	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
IL31RA	Q8NI17	1

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 2 evidence-associated genes (2 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 2 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	2	634.4×	2e-06	IL31RA, 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cytokine-mediated signaling pathway	2	130.6×	0.001	IL31RA, OSMR
defense response to other organism	1	8426.0×	0.001	IL31RA
oncostatin-M-mediated signaling pathway	1	2106.5×	0.003	OSMR
acute inflammatory response to antigenic stimulus	1	1404.3×	0.003	IL31RA
glandular epithelial cell differentiation	1	1053.2×	0.003	IL31RA
homeostatic process	1	842.6×	0.003	IL31RA
negative regulation of macrophage activation	1	842.6×	0.003	IL31RA
positive regulation of cell population proliferation	2	33.6×	0.003	IL31RA, OSMR
positive regulation of acute inflammatory response	1	702.2×	0.003	OSMR
monocyte differentiation	1	401.2×	0.005	IL31RA
positive regulation of tyrosine phosphorylation of STAT protein	1	366.4×	0.005	IL31RA
macrophage differentiation	1	234.1×	0.007	IL31RA
response to cytokine	1	187.2×	0.008	OSMR
cell surface receptor signaling pathway via JAK-STAT	1	145.3×	0.009	IL31RA
defense response	1	108.0×	0.012	IL31RA
cell surface receptor protein tyrosine kinase signaling pathway	1	86.9×	0.014	IL31RA
MAPK cascade	1	76.6×	0.015	IL31RA
negative regulation of apoptotic process	1	17.4×	0.060	IL31RA
positive regulation of DNA-templated transcription	1	14.0×	0.070	IL31RA

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 2 of 2 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
IL31RA	0	0
OSMR	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	1	IL31RA
D	Druggable family + AlphaFold only, no drug	1	OSMR
E	Difficult family or no structure, no drug	0

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)
IL31RA	0	—
OSMR	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01164241	Not specified	COMPLETED	Natural History of Severe Allergic Inflammation and Reactions