Amyloidosis, primary localized cutaneous, 3
disease diseaseOn this page
Also known as PLCA3
Summary
Amyloidosis, primary localized cutaneous, 3 (MONDO:0054765) is a disease caused by GPNMB (GenCC Definitive), with 1 cohort gene.
At a glance
- Causal gene: GPNMB (GenCC Definitive)
- Cohort genes: 1
- ClinVar variants: 16
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | amyloidosis, primary localized cutaneous, 3 |
| Mondo ID | MONDO:0054765 |
| OMIM | 617920 |
| UMLS | C4554421 |
| MedGen | 1640641 |
| GARD | 0025971 |
| Is cancer (heuristic) | no |
Also known as: PLCA3
Data availability: 16 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, 3
Related subtypes (2): amyloidosis, primary localized cutaneous, 2, amyloidosis, primary localized cutaneous, 1
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
16 retrieved; paginated sample, class counts are floors:
8 pathogenic, 5 likely pathogenic, 2 uncertain significance, 1 pathogenic/likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1324506 | NM_002510.3(GPNMB):c.319_332del (p.Lys107fs) | GPNMB | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 2577912 | NM_002510.3(GPNMB):c.1118-2A>G | GPNMB | Pathogenic | criteria provided, single submitter |
| 3382241 | NM_002510.3(GPNMB):c.393T>G (p.Tyr131Ter) | GPNMB | Pathogenic | criteria provided, single submitter |
| 503497 | NM_002510.3(GPNMB):c.565C>T (p.Arg189Ter) | GPNMB | Pathogenic | criteria provided, single submitter |
| 503498 | NM_002510.3(GPNMB):c.660T>G (p.Tyr220Ter) | GPNMB | Pathogenic | no assertion criteria provided |
| 503499 | NM_002510.3(GPNMB):c.1056del (p.Pro353fs) | GPNMB | Pathogenic | criteria provided, single submitter |
| 503500 | NM_002510.3(GPNMB):c.296del (p.Asn99fs) | GPNMB | Pathogenic | no assertion criteria provided |
| 503501 | NM_002510.3(GPNMB):c.719_720del (p.Val240fs) | GPNMB | Pathogenic | no assertion criteria provided |
| 503502 | NM_002510.3(GPNMB):c.877_880del (p.Val293fs) | GPNMB | Pathogenic | no assertion criteria provided |
| 3382360 | NM_002510.3(GPNMB):c.807del (p.Pro270fs) | GPNMB | Likely pathogenic | criteria provided, single submitter |
| 3779708 | NM_002510.3(GPNMB):c.1018+1G>A | GPNMB | Likely pathogenic | criteria provided, single submitter |
| 3779710 | NM_002510.3(GPNMB):c.742C>T (p.Arg248Ter) | GPNMB | Likely pathogenic | criteria provided, single submitter |
| 4845665 | NM_002510.3(GPNMB):c.1238G>C (p.Cys413Ser) | GPNMB | Likely pathogenic | criteria provided, single submitter |
| 983510 | NM_002510.3(GPNMB):c.1330C>T (p.Arg444Ter) | GPNMB | Likely pathogenic | criteria provided, single submitter |
| 3068175 | NM_002510.3(GPNMB):c.547T>G (p.Tyr183Asp) | GPNMB | Uncertain significance | criteria provided, single submitter |
| 3779709 | NM_002510.3(GPNMB):c.1019-12C>G | GPNMB | Uncertain significance | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 4 · 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 |
|---|---|---|---|---|
| GPNMB | Definitive | Autosomal recessive | amyloidosis, primary localized cutaneous, 3 | 4 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| GPNMB | Orphanet:319635 | Amyloidosis cutis dyschromia |
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 |
|---|---|---|---|---|---|
| GPNMB | HGNC:4462 | ENSG00000136235 | Q14956 | Transmembrane glycoprotein NMB | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| GPNMB | Transmembrane glycoprotein NMB | Could be a melanogenic enzyme. |
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) |
|---|---|---|---|---|
| GPNMB | Antibody/Immunoglobulin | yes | PKD_dom, Ig-like_fold, PKD/Chitinase_dom |
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 hip | 1 |
| tendon of biceps brachii | 1 |
| upper leg skin | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| GPNMB | 299 | ubiquitous | marker | upper leg skin, skin of hip, tendon of biceps brachii |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| GPNMB | 2,371 |
Structural data
PDB: 0 · AlphaFold-only: 1 · No structure: 0
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| GPNMB | Q14956 | 77.05 |
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 |
|---|---|---|---|---|
| PTK6 promotes HIF1A stabilization | 1 | 1631.4× | 6e-04 | GPNMB |
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 tissue remodeling | 1 | 2106.5× | 0.006 | GPNMB |
| positive chemotaxis | 1 | 802.5× | 0.006 | GPNMB |
| negative regulation of T cell activation | 1 | 526.6× | 0.006 | GPNMB |
| negative regulation of cytokine production | 1 | 510.7× | 0.006 | GPNMB |
| regulation of angiogenesis | 1 | 421.3× | 0.006 | GPNMB |
| negative regulation of G1/S transition of mitotic cell cycle | 1 | 358.6× | 0.006 | GPNMB |
| negative regulation of T cell proliferation | 1 | 330.4× | 0.006 | GPNMB |
| negative regulation of tumor necrosis factor production | 1 | 251.5× | 0.007 | GPNMB |
| positive regulation of ERK1 and ERK2 cascade | 1 | 85.1× | 0.018 | GPNMB |
| cell-cell signaling | 1 | 69.6× | 0.020 | GPNMB |
| positive regulation of cell migration | 1 | 61.7× | 0.021 | GPNMB |
| negative regulation of cell population proliferation | 1 | 42.1× | 0.028 | GPNMB |
| cell adhesion | 1 | 37.5× | 0.029 | GPNMB |
| signal transduction | 1 | 16.1× | 0.062 | GPNMB |
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 |
|---|---|---|
| GPNMB | 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 | GPNMB |
| 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) |
|---|---|---|
| GPNMB | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.
Related Atlas pages
- Cohort genes: GPNMB