Aortic aneurysm, familial abdominal, 1

Summary

Aortic aneurysm, familial abdominal, 1 (MONDO:0024521) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	aortic aneurysm, familial abdominal, 1
Mondo ID	MONDO:0024521
OMIM	100070
UMLS	C1853365
MedGen	339961
GARD	0016491
Is cancer (heuristic)	no

Also known as: AAA1 · aortic aneurysm, familial abdominal 1 · aortic aneurysm, familial abdominal, 1

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › familial abdominal aortic aneurysm › aortic aneurysm, familial abdominal, 1

Related subtypes (3): aortic aneurysm, familial abdominal, 2, aortic aneurysm, familial abdominal, 3, aortic aneurysm, familial abdominal, 4

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

1 retrieved; paginated sample, class counts are floors:

1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
180446	NM_053025.4(MYLK):c.4844C>T (p.Ala1615Val)	MYLK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MYLK	Orphanet:2241	Megacystis-microcolon-intestinal hypoperistalsis syndrome
MYLK	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
MYLK	HGNC:7590	ENSG00000065534	Q15746	Myosin light chain kinase, smooth muscle	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MYLK	Myosin light chain kinase, smooth muscle	Calcium/calmodulin-dependent myosin light chain kinase implicated in smooth muscle contraction via phosphorylation of myosin light chains (MLC).

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
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MYLK	Kinase	yes	2.7.11.18	Prot_kinase_dom, Ig_sub2, Ig_sub

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
cauda epididymis	1
saphenous vein	1
seminal vesicle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MYLK	289	ubiquitous	marker	cauda epididymis, saphenous vein, seminal vesicle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MYLK	2,763

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MYLK	Q15746	8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. 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
RHO GTPases activate PAKs	1	543.8×	0.013	MYLK
Smooth Muscle Contraction	1	265.6×	0.013	MYLK
Muscle contraction	1	77.2×	0.026	MYLK
RHO GTPase Effectors	1	68.0×	0.026	MYLK
Signaling by Rho GTPases	1	34.2×	0.035	MYLK
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	33.5×	0.035	MYLK
Signal Transduction	1	10.2×	0.098	MYLK

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
tonic smooth muscle contraction	1	16852.0×	6e-04	MYLK
aorta smooth muscle tissue morphogenesis	1	4213.0×	0.001	MYLK
bleb assembly	1	1532.0×	0.002	MYLK
cellular hypotonic response	1	1404.3×	0.002	MYLK
regulation of synaptic vesicle endocytosis	1	887.0×	0.002	MYLK
smooth muscle contraction	1	802.5×	0.002	MYLK
positive regulation of calcium ion transport	1	581.1×	0.002	MYLK
positive regulation of wound healing	1	526.6×	0.002	MYLK
protein phosphorylation	1	68.0×	0.016	MYLK
positive regulation of cell migration	1	61.7×	0.016	MYLK

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
MYLK	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MYLK	28	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	MYLK
AFATINIB	4	MYLK
FEDRATINIB	4	MYLK
RUXOLITINIB	4	MYLK
NIFEDIPINE	4	MYLK
BOSUTINIB	4	MYLK
GILTERITINIB	4	MYLK
TOVORAFENIB	4	MYLK
NINTEDANIB	4	MYLK
SUNITINIB	4	MYLK
DASATINIB	4	MYLK
QUIZARTINIB	4	MYLK
MIDOSTAURIN	4	MYLK
FASUDIL	3	MYLK
DOVITINIB	3	MYLK
LESTAURTINIB	3	MYLK
RUBOXISTAURIN	3	MYLK
VX-702	2	MYLK
SU-014813	2	MYLK
REBASTINIB	2	MYLK
TANZISERTIB	2	MYLK
CEP-32496	2	MYLK
BAFETINIB	2	MYLK
PEXMETINIB	2	MYLK
R-406	2	MYLK
BI-2536	2	MYLK
KW-2449	1	MYLK
IMD-0354	1	MYLK

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
MYLK	303	Binding:303

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
MYLK	2.7.11.18	myosin-light-chain kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
MYLK	303

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

28 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.

Compound	Max phase	Cohort target (bioactivity)
PONATINIB	4	MYLK
AFATINIB	4	MYLK
FEDRATINIB	4	MYLK
RUXOLITINIB	4	MYLK
NIFEDIPINE	4	MYLK
BOSUTINIB	4	MYLK
GILTERITINIB	4	MYLK
TOVORAFENIB	4	MYLK
NINTEDANIB	4	MYLK
SUNITINIB	4	MYLK
DASATINIB	4	MYLK
QUIZARTINIB	4	MYLK
MIDOSTAURIN	4	MYLK
FASUDIL	3	MYLK
DOVITINIB	3	MYLK
LESTAURTINIB	3	MYLK
RUBOXISTAURIN	3	MYLK
VX-702	2	MYLK
SU-014813	2	MYLK
REBASTINIB	2	MYLK
TANZISERTIB	2	MYLK
CEP-32496	2	MYLK
BAFETINIB	2	MYLK
PEXMETINIB	2	MYLK
R-406	2	MYLK
BI-2536	2	MYLK
KW-2449	1	MYLK
IMD-0354	1	MYLK

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	MYLK
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	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.