Aortic aneurysm, familial thoracic 9

disease

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Also known as AAT9aortic aneurysm, familial thoracic type 9familial thoracic aortic aneurysm and aortic dissection caused by mutation in MFAP5MFAP5 familial thoracic aortic aneurysm and aortic dissection

Summary

Aortic aneurysm, familial thoracic 9 (MONDO:0014514) is a disease caused by MFAP5 (GenCC Strong), with 1 cohort gene and 1 clinical trial.

At a glance

Causal gene: MFAP5 (GenCC Strong)
Cohort genes: 1
ClinVar variants: 15
Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	aortic aneurysm, familial thoracic 9
Mondo ID	MONDO:0014514
OMIM	616166
UMLS	C4015368
MedGen	863805
GARD	0016067
Is cancer (heuristic)	no

Also known as: AAT9 · aortic aneurysm, familial thoracic 9 · aortic aneurysm, familial thoracic type 9 · familial thoracic aortic aneurysm and aortic dissection caused by mutation in MFAP5 · MFAP5 familial thoracic aortic aneurysm and aortic dissection

Data availability: 15 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › familial thoracic aortic aneurysm and aortic dissection › aortic aneurysm, familial thoracic 9

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

15 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
2581013	NM_003480.4(MFAP5):c.264del (p.Lys88fs)	MFAP5	Likely pathogenic	criteria provided, single submitter
162199	NM_003480.4(MFAP5):c.472C>T (p.Arg158Ter)	LOC126861443	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1033583	NM_003480.4(MFAP5):c.2T>C (p.Met1Thr)	MFAP5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1586100	NM_003480.4(MFAP5):c.236A>T (p.Asn79Ile)	MFAP5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
162200	NM_003480.4(MFAP5):c.62G>T (p.Trp21Leu)	MFAP5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
390582	NM_003480.4(MFAP5):c.12G>A (p.Leu4=)	MFAP5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1738328	NM_003480.4(MFAP5):c.415C>T (p.Leu139Phe)	MFAP5	Uncertain significance	criteria provided, multiple submitters, no conflicts
2780951	NM_003480.4(MFAP5):c.152A>T (p.Asp51Val)	MFAP5	Uncertain significance	criteria provided, multiple submitters, no conflicts
432423	NM_003480.4(MFAP5):c.395A>T (p.His132Leu)	MFAP5	Uncertain significance	criteria provided, multiple submitters, no conflicts
392223	NM_003480.4(MFAP5):c.410-18G>A	LOC126861443	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
1643524	NM_003480.4(MFAP5):c.94+18T>G	MFAP5	Likely benign	criteria provided, multiple submitters, no conflicts
381191	NM_003480.4(MFAP5):c.172+5A>G	MFAP5	Benign	criteria provided, multiple submitters, no conflicts
388139	NM_003480.4(MFAP5):c.6G>A (p.Ser2=)	MFAP5	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
506515	NM_003480.4(MFAP5):c.195T>A (p.Ile65=)	MFAP5	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
507380	NM_003480.4(MFAP5):c.336-9C>T	MFAP5	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

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
MFAP5	Strong	Autosomal dominant	aortic aneurysm, familial thoracic 9	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MFAP5	Orphanet:91387	Familial thoracic aortic aneurysm and aortic dissection

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
MFAP5	HGNC:29673	ENSG00000197614	Q13361	Microfibrillar-associated protein 5	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MFAP5	Microfibrillar-associated protein 5	May play a role in hematopoiesis.

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)
MFAP5	Other/Unknown	no		MAGP

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
synovial joint	1
tibial nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MFAP5	236	broad	marker	synovial joint, skin of hip, tibial nerve

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MFAP5	1,110

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MFAP5	Q13361	65.79

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Elastic fibre formation	1	335.9×	0.005	MFAP5
Molecules associated with elastic fibres	1	308.6×	0.005	MFAP5
Extracellular matrix organization	1	63.1×	0.016	MFAP5

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
embryonic eye morphogenesis	1	1532.0×	0.001	MFAP5
supramolecular fiber organization	1	1053.2×	0.001	MFAP5
definitive hemopoiesis	1	936.2×	0.001	MFAP5

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MFAP5	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	MFAP5

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)
MFAP5	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
NCT05636527	Not specified	RECRUITING	Further Evaluation of Safety and Performance of the NEXUS Aortic Arch Stent Graft System and the Custom-Made NEXUS Multibranch™ Aortic Arch Stent Graft System

Cohort genes: MFAP5