Fibromuscular dysplasia, multifocal

Summary

Fibromuscular dysplasia, multifocal (MONDO:0859151) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 237

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	fibromuscular dysplasia, multifocal
Mondo ID	MONDO:0859151
OMIM	619329
UMLS	C5543412
MedGen	1778238
Is cancer (heuristic)	no

Data availability: 237 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › vascular disorder › arterial disorder › fibromuscular dysplasia, multifocal

Related subtypes (29): vertebral artery insufficiency, splenic artery aneurysm, basilar artery insufficiency, arteriosclerosis disorder, subclavian artery aneurysm, pulmonary artery choriocarcinoma, pulmonary artery leiomyosarcoma, coronary artery disorder, hypertensive disorder, carotid artery disorder, pulmonary embolism, peripheral arterial disease, hypotensive disorder, large artery stroke, aortic disorder, cervical artery dissection, anterior spinal artery syndrome, fibromuscular dysplasia, retinal arterial tortuosity, Sneddon syndrome, celiac trunk compression syndrome, pediatric arterial ischemic stroke, absence of the pulmonary artery, arterial occlusion, aberrant subclavian artery, anterior spinal artery stroke, arteritis, pulmonary artery disease, carotid web

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

237 retrieved; paginated sample, class counts are floors:

127 benign/likely benign, 58 benign, 27 conflicting classifications of pathogenicity, 15 uncertain significance, 4 likely benign, 3 pathogenic/likely pathogenic, 2 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1527853	NM_000093.5(COL5A1):c.2153del (p.Gly718fs)	COL5A1	Pathogenic	criteria provided, single submitter
3382097	NM_000093.5(COL5A1):c.1269del (p.Thr424fs)	COL5A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
827999	NM_000093.5(COL5A1):c.5386C>T (p.Gln1796Ter)	COL5A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
971716	NM_000093.5(COL5A1):c.196C>T (p.Arg66Ter)	COL5A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
213035	NM_000093.5(COL5A1):c.5357dup (p.Asp1787fs)	LOC101448202	Pathogenic	criteria provided, multiple submitters, no conflicts
4819596	NM_000093.5(COL5A1):c.1700del (p.Thr567fs)	COL5A1	Likely pathogenic	criteria provided, single submitter
1353147	NM_000093.5(COL5A1):c.700T>C (p.Tyr234His)	COL5A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
136888	NM_000093.5(COL5A1):c.4068+7G>A	COL5A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1455270	NM_000093.5(COL5A1):c.2646+18T>A	COL5A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
212936	NM_000093.5(COL5A1):c.1595C>T (p.Ala532Val)	COL5A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
212949	NM_000093.5(COL5A1):c.2354C>T (p.Pro785Leu)	COL5A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
212952	NM_000093.5(COL5A1):c.2947G>A (p.Glu983Lys)	COL5A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
212955	NM_000093.5(COL5A1):c.3110C>T (p.Thr1037Met)	COL5A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
212960	NM_000093.5(COL5A1):c.3292G>A (p.Ala1098Thr)	COL5A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
212972	NM_000093.5(COL5A1):c.4162C>T (p.Pro1388Ser)	COL5A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
212977	NM_000093.5(COL5A1):c.4307C>T (p.Pro1436Leu)	COL5A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
212990	NM_000093.5(COL5A1):c.4765G>A (p.Ala1589Thr)	COL5A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
212994	NM_000093.5(COL5A1):c.4879C>T (p.Arg1627Trp)	COL5A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
236997	NM_000093.5(COL5A1):c.1540G>A (p.Gly514Ser)	COL5A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
365710	NM_000093.5(COL5A1):c.1270A>G (p.Thr424Ala)	COL5A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
373260	NM_000093.5(COL5A1):c.2722C>T (p.Pro908Ser)	COL5A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
380308	NM_000093.5(COL5A1):c.4586C>A (p.Pro1529His)	COL5A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
426317	NM_000093.5(COL5A1):c.3260G>C (p.Gly1087Ala)	COL5A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
459682	NM_000093.5(COL5A1):c.3812C>T (p.Pro1271Leu)	COL5A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
519643	NM_000093.5(COL5A1):c.1304C>T (p.Pro435Leu)	COL5A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
571553	NM_000093.5(COL5A1):c.935C>T (p.Pro312Leu)	COL5A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
701246	NM_000093.5(COL5A1):c.1967C>T (p.Pro656Leu)	COL5A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
992509	NM_000093.5(COL5A1):c.5137-8C>T	COL5A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1000461	NM_000093.5(COL5A1):c.4795G>A (p.Glu1599Lys)	LOC101448202	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
213054	NM_000093.5(COL5A1):c.4522C>A (p.Pro1508Thr)	LOC101448202	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COL5A1	Orphanet:287	Classical Ehlers-Danlos 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
COL5A1	HGNC:2209	ENSG00000130635	P20908	Collagen alpha-1(V) chain	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COL5A1	Collagen alpha-1(V) chain	Type V collagen is a member of group I collagen (fibrillar forming collagen).

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
COL5A1	Other/Unknown	no		Fib_collagen_C, Laminin_G, Collagen

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
periodontal ligament	1
stromal cell of endometrium	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COL5A1	248	ubiquitous	marker	stromal cell of endometrium, periodontal ligament, tendon of biceps brachii

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COL5A1	2,600

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
COL5A1	P20908	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 14. 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
Fibronectin matrix formation	1	571.0×	0.007	COL5A1
Attachment of bacteria to epithelial cells	1	496.5×	0.007	COL5A1
Syndecan interactions	1	423.0×	0.007	COL5A1
MET activates PTK2 signaling	1	380.7×	0.007	COL5A1
Collagen chain trimerization	1	259.6×	0.007	COL5A1
Signaling by PDGF	1	253.8×	0.007	COL5A1
NCAM1 interactions	1	248.3×	0.007	COL5A1
Developmental Lineage of Pancreatic Ductal Cells	1	228.4×	0.007	COL5A1
Assembly of collagen fibrils and other multimeric structures	1	200.3×	0.007	COL5A1
Collagen degradation	1	175.7×	0.007	COL5A1
Collagen biosynthesis and modifying enzymes	1	170.4×	0.007	COL5A1
Non-integrin membrane-ECM interactions	1	154.3×	0.007	COL5A1
ECM proteoglycans	1	150.3×	0.007	COL5A1
Integrin cell surface interactions	1	134.3×	0.007	COL5A1

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
integrin biosynthetic process	1	16852.0×	8e-04	COL5A1
negative regulation of endodermal cell differentiation	1	8426.0×	8e-04	COL5A1
tendon development	1	4213.0×	8e-04	COL5A1
eye morphogenesis	1	4213.0×	8e-04	COL5A1
collagen biosynthetic process	1	1053.2×	0.002	COL5A1
wound healing, spreading of epidermal cells	1	1053.2×	0.002	COL5A1
supramolecular fiber organization	1	1053.2×	0.002	COL5A1
skin development	1	443.5×	0.003	COL5A1
blood vessel development	1	374.5×	0.003	COL5A1
heart morphogenesis	1	374.5×	0.003	COL5A1
collagen fibril organization	1	224.7×	0.005	COL5A1
cell migration	1	61.5×	0.018	COL5A1
cell adhesion	1	37.5×	0.027	COL5A1

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
COL5A1	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	COL5A1

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)
COL5A1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.