Coronary artery disease, autosomal dominant, 1

Summary

Coronary artery disease, autosomal dominant, 1 (MONDO:0012011) is a disease with 1 cohort gene and 1 clinical trial.

At a glance

• Cohort genes: 1
• ClinVar variants: 6
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	coronary artery disease, autosomal dominant, 1
Mondo ID	MONDO:0012011
MeSH	C564258
OMIM	608320
UMLS	C1842247
MedGen	330802
Is cancer (heuristic)	no

Also known as: ADCAD1 · coronary artery disease caused by mutation in MEF2A · coronary artery disease, autosomal dominant, 1 · coronary artery disease, autosomal dominant, type 1 · MEF2A coronary artery disease

Data availability: 6 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › vascular disorder › arterial disorder › coronary artery disorder › coronary artery disease, autosomal dominant, 1

Related subtypes (11): coronary vasospasm, postoperative ventricular dysfunction, coronary aneurysm, coronary stenosis, coronary thrombosis, intermediate coronary syndrome, coronary artery disease, autosomal dominant 2, coronary artery congenital malformation, coronary atherosclerosis, nonobstructive coronary artery disease, fibromuscular dysplasia of the coronary arteries

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

6 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 2 pathogenic, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
8948	NM_001319206.4(MEF2A):c.1313_1333del (p.Gln438_Pro444del)	MEF2A	Pathogenic	no assertion criteria provided
8949	NM_001319206.4(MEF2A):c.830C>T (p.Pro277Leu)	MEF2A	Pathogenic	criteria provided, single submitter
3064723	NM_001319206.4(MEF2A):c.407A>G (p.Gln136Arg)	MEF2A	Uncertain significance	criteria provided, single submitter
3891652	NM_001319206.4(MEF2A):c.1253AGC[5] (p.Gln423_Gln428del)	MEF2A	Uncertain significance	criteria provided, single submitter
3891653	NM_001319206.4(MEF2A):c.1293ACC[1] (p.Pro433del)	MEF2A	Uncertain significance	criteria provided, single submitter
778574	NM_001319206.4(MEF2A):c.1253AGC[13] (p.Gln427_Gln428dup)	MEF2A	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · Orphanet: 0 · 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
MEF2A	Limited	Autosomal dominant	coronary artery disease, autosomal dominant, 1

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
MEF2A	HGNC:6993	ENSG00000068305	Q02078	Myocyte-specific enhancer factor 2A	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MEF2A	Myocyte-specific enhancer factor 2A	Transcriptional activator which binds specifically to the MEF2 element, 5’-YTAATTAR-3’, found in numerous muscle-specific genes.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MEF2A	Transcription factor	no		TF_MADSbox, HJURP_C, MEF2-like_N

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
calcaneal tendon	1
cardiac muscle of right atrium	1
myocardium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MEF2A	291	ubiquitous	marker	calcaneal tendon, myocardium, cardiac muscle of right atrium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MEF2A	2,903

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MEF2A	Q02078	10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 31. 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
ERK/MAPK targets	1	671.8×	0.009	MEF2A
MAPK targets/ Nuclear events mediated by MAP kinases	1	543.8×	0.009	MEF2A
Myogenesis	1	380.7×	0.009	MEF2A
Nuclear Events (kinase and transcription factor activation)	1	346.1×	0.009	MEF2A
MAP kinase activation	1	308.6×	0.009	MEF2A
Interleukin-17 signaling	1	253.8×	0.009	MEF2A
Toll Like Receptor 10 (TLR10) Cascade	1	215.5×	0.009	MEF2A
Toll Like Receptor 5 (TLR5) Cascade	1	215.5×	0.009	MEF2A
MyD88 cascade initiated on plasma membrane	1	203.9×	0.009	MEF2A
Signaling by NTRK1 (TRKA)	1	196.9×	0.009	MEF2A
Toll Like Receptor 3 (TLR3) Cascade	1	193.6×	0.009	MEF2A
TRIF (TICAM1)-mediated TLR4 signaling	1	190.3×	0.009	MEF2A
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation	1	190.3×	0.009	MEF2A
MyD88 dependent cascade initiated on endosome	1	190.3×	0.009	MEF2A
MyD88-independent TLR4 cascade	1	184.2×	0.009	MEF2A
Toll Like Receptor 7/8 (TLR7/8) Cascade	1	184.2×	0.009	MEF2A
Signaling by NTRKs	1	181.3×	0.009	MEF2A
Toll Like Receptor 9 (TLR9) Cascade	1	175.7×	0.009	MEF2A
Toll Like Receptor TLR6:TLR2 Cascade	1	175.7×	0.009	MEF2A
Toll Like Receptor 2 (TLR2) Cascade	1	173.0×	0.009	MEF2A
Toll Like Receptor TLR1:TLR2 Cascade	1	167.9×	0.009	MEF2A
MyD88:MAL(TIRAP) cascade initiated on plasma membrane	1	152.3×	0.009	MEF2A
Toll Like Receptor 4 (TLR4) Cascade	1	131.3×	0.010	MEF2A
Toll-like Receptor Cascades	1	124.1×	0.010	MEF2A
Signaling by Interleukins	1	64.2×	0.019	MEF2A
Signaling by Receptor Tyrosine Kinases	1	51.7×	0.023	MEF2A
Cytokine Signaling in Immune system	1	40.8×	0.028	MEF2A
Innate Immune System	1	25.5×	0.043	MEF2A
Developmental Biology	1	14.5×	0.074	MEF2A
Immune System	1	13.0×	0.080	MEF2A

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
ventricular cardiac myofibril assembly	1	5617.3×	0.003	MEF2A
mitochondrion distribution	1	2106.5×	0.003	MEF2A
cardiac conduction	1	1685.2×	0.003	MEF2A
muscle cell development	1	936.2×	0.004	MEF2A
positive regulation of cardiac muscle hypertrophy	1	732.7×	0.004	MEF2A
positive regulation of D-glucose import across plasma membrane	1	455.5×	0.005	MEF2A
dendrite morphogenesis	1	432.1×	0.005	MEF2A
DNA-templated transcription	1	224.7×	0.009	MEF2A
cellular response to calcium ion	1	200.6×	0.009	MEF2A
muscle organ development	1	166.8×	0.010	MEF2A
heart development	1	78.8×	0.018	MEF2A
positive regulation of gene expression	1	38.7×	0.034	MEF2A
cell differentiation	1	29.1×	0.040	MEF2A
apoptotic process	1	28.7×	0.040	MEF2A
negative regulation of transcription by RNA polymerase II	1	17.7×	0.060	MEF2A
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	MEF2A

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
MEF2A	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	MEF2A

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)
MEF2A	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE4	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00846846	PHASE4	COMPLETED	PROTECT Continued Access Post Marketing Surveillance Trial