Myocardial infarction

Summary

Myocardial infarction (MONDO:0005068) is a disease (an umbrella term covering 14 Mondo subtypes) with 75 cohort genes (1,185 GWAS associations across 78 studies) and 1,384 clinical trials. The dominant Reactome pathway is Signaling by PDGF (8 cohort genes). Top therapeutic interventions include abciximab, clopidogrel, and prasugrel.

At a glance

• Umbrella term: 14 Mondo subtypes
• Cohort genes: 75
• GWAS associations: 1,185
• ClinVar variants: 2
• Clinical trials: 1,384

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	myocardial infarction
Mondo ID	MONDO:0005068
EFO	EFO:0000612
MeSH	D009203
DOID	DOID:5844
ICD-10-CM	I21
NCIT	C27996
SNOMED CT	22298006
UMLS	C0027051
MedGen	10150
Anatomy (UBERON)	UBERON:0000948
Is cancer (heuristic)	no

Also known as: heart attack · infarction (MI), myocardial · MI · MI, myocardial infarction · myocardial infarct · myocardial infarction · myocardial infarction (disease) · myocardial infarction, (MI)

Data availability: 2 ClinVar variants · 1,185 GWAS associations (78 studies) · 1 HPO phenotype · 18 cell lines.

Disease family

An umbrella term covering 14 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › heart disorder › myocardial disorder › myocardial infarction

Related subtypes (4): myocarditis, conduction system disorder, neoplasm of myocardium, myocardial ischemia

Subtypes (14): posteroinferior myocardial infarction, septal myocardial infarction, posterior myocardial infarction, apical myocardial infarction, subendocardial myocardial infarction, posterolateral myocardial infarction, inferolateral myocardial infarct, lateral myocardial infarction, silent myocardial infarction, anteroseptal myocardial infarction, acute myocardial infarction, myocardial stunning, anterolateral myocardial infarction, inferior myocardial infarction

Genetics & variants

GWAS landscape

1,185 GWAS associations across 78 studies. Top hits map to 31 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs2891168	2e-141	CDKN2B-AS1	G	1.21
rs4977574	5e-128	CDKN2B-AS1	?	0.84
chr9:22093299	1e-103		A	0.16
rs671	1e-101	ALDH2	A	0.33
rs10455872	6e-94	LPA	A	0.27
rs1556516	9e-76	CDKN2B-AS1	G	0.15
rs1537373	2e-71	CDKN2B-AS1	T	0.16
rs9349379	4e-63	PHACTR1	G	0.15
rs1479299386	1e-62	CDKN2B-AS1	?	0.88
rs4007642	2e-58	CDKN2B-AS1	?
rs4252185	7e-58	PLG	?	0.78
rs55730499	1e-55	LPA	T	0.36
rs117121174	1e-36	IFT81 - ATP2A2	A	0.29
rs2378584	6e-35	MIA3	G	0.11
rs13306206	5e-33	APOB	A	0.49
rs140570886	9e-33	LPA	?
rs12740374	8e-32	CELSR2	G	1.11
chr1:109821511	5e-29		T	0.1
rs9515203	6e-28	COL4A2	T	0.09
rs7528419	4e-27	CELSR2	A	0.1
rs200787930	9e-26	PLCB2	C	100
rs188378669	1e-25	CXCL8	G	100
rs61734696	2e-25	MARCHF1, ANP32CP	G	100
rs199921354	2e-25	VPS33B, VPS33B-DT	C	100
rs12190287	3e-25	TCF21, TARID	G	0.09
rs115287176	9e-25	TMOD4	G	100
rs146092501	1e-24	COL6A3	C	50
rs146879198	1e-24	ZNF77	G	50
rs2315065	2e-24	LPA - PLG	A	1.3
rs35700460	2e-24	MIA3	G	1.09

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST003117	Nikpay M	2015	27,509	99,121	A comprehensive 1,000 Genomes-based genome-wide association meta-analysis of coronary artery disease.
GCST90473536	UK Biobank Whole-Genome Sequencing Consortium	2025	23,055	435,385	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90018877	Sakaue S	2021	20,917	440,906	A cross-population atlas of genetic associations for 220 human phenotypes.
GCST90081495	Backman JD	2021	17,896	404,595	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90085481	Backman JD	2021	17,896	404,595	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90446532	Guo Y	2023	16,602	442,536	Genome-Wide Assessment of Shared Genetic Architecture Between Rheumatoid Arthritis and Cardiovascular Diseases.
GCST90081494	Backman JD	2021	15,475	348,048	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90085480	Backman JD	2021	15,475	348,048	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90018657	Sakaue S	2021	14,992	146,214	A cross-population atlas of genetic associations for 220 human phenotypes.
GCST011364	Hartiala JA	2021	14,825	380,970	Genome-wide analysis identifies novel susceptibility loci for myocardial infarction.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	10
Tier 2: splice/UTR	3
Tier 3: regulatory	1
Tier 4: intronic/intergenic	36

MAF distribution

Bucket	Variants
common (>=0.05)	39
low_freq (0.01-0.05)	2
rare (<0.01)	0
unknown	9

Functional consequences

Consequence	Count
intron_variant	28
missense_variant	8
intergenic_variant	4
3_prime_UTR_variant	3
unknown	2
stop_gained	2
non_coding_transcript_exon_variant	2
regulatory_region_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs2891168	9	22098620	A>G	0.483	intron_variant	CDKN2B-AS1	2e-141	Tier 4: intronic/intergenic
rs4977574	9	22098575	A>G,T	0.05	intron_variant	CDKN2B-AS1	5e-128	Tier 4: intronic/intergenic
chr9:22093299				0.487			1e-103	Tier 4: intronic/intergenic
rs671	12	111803962	G>A	0.238	missense_variant	ALDH2	1e-101	Tier 1: coding
rs10455872	6	160589086	A>G	0.069	intron_variant	LPA	6e-94	Tier 4: intronic/intergenic
rs1556516	9	22100177	G>A,C,T	0.442	intron_variant	CDKN2B-AS1	9e-76	Tier 4: intronic/intergenic
rs1537373	9	22103342	T>A,G	0.443	intron_variant	CDKN2B-AS1	2e-71	Tier 4: intronic/intergenic
rs9349379	6	12903725	A>C,G,T	0.05	intron_variant	PHACTR1	4e-63	Tier 4: intronic/intergenic
rs1479299386	9	21997874	G>GA		intron_variant	CDKN2B-AS1	1e-62	Tier 4: intronic/intergenic
rs4007642	9	22093300	A>C,T	0.05	intron_variant	CDKN2B-AS1	2e-58	Tier 4: intronic/intergenic
rs4252185	6	160702419	T>C	0.05	intron_variant	PLG	7e-58	Tier 4: intronic/intergenic
rs55730499	6	160584578	C>T	0.05	intron_variant	LPA	1e-55	Tier 4: intronic/intergenic
rs117121174	12	110259525	G>A	0.05	intron_variant	IFT81 - ATP2A2	1e-36	Tier 4: intronic/intergenic
rs2378584	1	222620290	A>G,T	0.05	intron_variant	MIA3	6e-35	Tier 4: intronic/intergenic
rs13306206	2	21019859	G>A,C,T	0.035	missense_variant	APOB	5e-33	Tier 1: coding
rs140570886	6	160591981	T>C	0.05	intron_variant	LPA	9e-33	Tier 4: intronic/intergenic
rs12740374	1	109274968	G>T	0.212	3_prime_UTR_variant	CELSR2	8e-32	Tier 2: splice/UTR
chr1:109821511				0.217			5e-29	Tier 4: intronic/intergenic
rs9515203	13	110397276	T>C	0.262	intron_variant	COL4A2	6e-28	Tier 4: intronic/intergenic
rs7528419	1	109274570	A>G	0.226	3_prime_UTR_variant	CELSR2	4e-27	Tier 2: splice/UTR
rs200787930	15	40289298	C>T		missense_variant	PLCB2	9e-26	Tier 1: coding
rs188378669	4	73741568	G>A,T		stop_gained	CXCL8	1e-25	Tier 1: coding
rs61734696	4	164197303	G>T		non_coding_transcript_exon_variant	MARCHF1, ANP32CP	2e-25	Tier 4: intronic/intergenic
rs199921354	15	91013841	C>T		missense_variant	VPS33B, VPS33B-DT	2e-25	Tier 1: coding
rs12190287	6	133893387	C>A,G,T	0.05	3_prime_UTR_variant	TCF21, TARID	3e-25	Tier 2: splice/UTR
rs115287176	1	151170961	G>A		missense_variant	TMOD4	9e-25	Tier 1: coding
rs146092501	2	237371861	C>T		missense_variant	COL6A3	1e-24	Tier 1: coding
rs146879198	19	2934109	G>A,T		stop_gained	ZNF77	1e-24	Tier 1: coding
rs2315065	6	160687112	C>A,T	0.06	intergenic_variant	LPA - PLG	2e-24	Tier 4: intronic/intergenic
rs35700460	1	222638065	A>C,G	0.326	intron_variant	MIA3	2e-24	Tier 4: intronic/intergenic

ClinVar germline variants

2 retrieved; paginated sample, class counts are floors:

2 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
35627	NM_020297.4(ABCC9):c.2200G>A (p.Val734Ile)	ABCC9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
209139	NM_000083.3(CLCN1):c.568_569delinsTC (p.Gly190Ser)	CLCN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 52 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RNF13	Orphanet:544503	RNF13-related severe early-onset epileptic encephalopathy
CNNM2	Orphanet:620363	Primary hypomagnesemia-generalized seizures-intellectual disability-obesity syndrome
ATXN2	Orphanet:803	Amyotrophic lateral sclerosis
ATXN2	Orphanet:98756	Spinocerebellar ataxia type 2
BMP1	Orphanet:216812	Osteogenesis imperfecta type 3
BMP1	Orphanet:314029	High bone mass osteogenesis imperfecta
SEC24D	Orphanet:2050	Cole-Carpenter syndrome
SEC24D	Orphanet:216796	Osteogenesis imperfecta type 1
SKI	Orphanet:1606	1p36 deletion syndrome
SKI	Orphanet:2462	Shprintzen-Goldberg syndrome
STAT3	Orphanet:2314	Autosomal dominant hyper-IgE syndrome due to STAT3 deficiency
STAT3	Orphanet:438159	STAT3-related early-onset multisystem autoimmune disease
STAT3	Orphanet:512017	Chronic lymphoproliferative disorder of natural killer cells
STAT3	Orphanet:520	Acute promyelocytic leukemia
STAT3	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
STAT3	Orphanet:86872	T-cell large granular lymphocyte leukemia
STAT3	Orphanet:99885	Isolated permanent neonatal diabetes mellitus
TBX20	Orphanet:54260	Left ventricular noncompaction
TBX20	Orphanet:99103	Atrial septal defect, ostium secundum type
TBXAS1	Orphanet:1802	Ghosal hematodiaphyseal dysplasia
HNF1A	Orphanet:319303	Chromophobe renal cell carcinoma
HNF1A	Orphanet:324575	Hyperinsulinism due to HNF1A deficiency
HNF1A	Orphanet:404511	Clear cell papillary renal cell carcinoma
HNF1A	Orphanet:552	MODY
GIGYF2	Orphanet:411602	Hereditary late-onset Parkinson disease
VPS33B	Orphanet:2697	Arthrogryposis-renal dysfunction-cholestasis syndrome
PRDM16	Orphanet:154	Familial isolated dilated cardiomyopathy
PRDM16	Orphanet:1606	1p36 deletion syndrome
PRDM16	Orphanet:54260	Left ventricular noncompaction
HDAC4	Orphanet:1001	2q37 microdeletion syndrome
BCAS3	Orphanet:697067	Global developmental delay-intellectual disability-microcephaly-short stature-brain iron accumulation syndrome
ZEB2	Orphanet:261537	Mowat-Wilson syndrome due to monosomy 2q22
ZEB2	Orphanet:261552	Mowat-Wilson syndrome due to a ZEB2 point mutation
ZEB2	Orphanet:626	Large/giant congenital melanocytic nevus
SERPINH1	Orphanet:216812	Osteogenesis imperfecta type 3
ZNF335	Orphanet:329228	Microcephalic primordial dwarfism due to ZNF335 deficiency
CCR1	Orphanet:117	Behçet disease
SCARB1	Orphanet:181428	Familial Hyperalphalipoproteinemia
IFITM5	Orphanet:216828	Osteogenesis imperfecta type 5
ZFPM2	Orphanet:2140	Congenital diaphragmatic hernia
ZFPM2	Orphanet:251510	46,XY partial gonadal dysgenesis
ZFPM2	Orphanet:3303	Tetralogy of Fallot
CDKN2A	Orphanet:1333	Familial pancreatic carcinoma
CDKN2A	Orphanet:1501	Adrenocortical carcinoma
CDKN2A	Orphanet:252206	Melanoma and neural system tumor syndrome
CDKN2A	Orphanet:404560	Familial atypical multiple mole melanoma syndrome
CDKN2A	Orphanet:524	Li-Fraumeni syndrome
CDKN2A	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
CDKN2A	Orphanet:618	Familial melanoma
CDKN2A	Orphanet:99861	Precursor T-cell acute lymphoblastic leukemia

Cohort genes → proteins

75 cohort genes, 74 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	75

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RNF13	HGNC:10057	ENSG00000082996	O43567	E3 ubiquitin-protein ligase RNF13	gwas
CNNM2	HGNC:103	ENSG00000148842	Q9H8M5	Metal transporter CNNM2	gwas
ATXN2	HGNC:10555	ENSG00000204842	Q99700	Ataxin-2	gwas
BMP1	HGNC:1067	ENSG00000168487	P13497	Bone morphogenetic protein 1	gwas
CXCL12	HGNC:10672	ENSG00000107562	P48061	Stromal cell-derived factor 1	gwas
SEC24D	HGNC:10706	ENSG00000150961	O94855	Protein transport protein Sec24D	gwas
SF3A2	HGNC:10766	ENSG00000104897	Q15428	Splicing factor 3A subunit 2	gwas
SKI	HGNC:10896	ENSG00000157933	P12755	Ski oncogene	gwas
SLC22A4	HGNC:10968	ENSG00000197208	Q9H015	Solute carrier family 22 member 4	gwas
BRAP	HGNC:1099	ENSG00000089234	Q7Z569	BRCA1-associated protein	gwas
SLC5A3	HGNC:11038	ENSG00000198743	P53794	Sodium/myo-inositol cotransporter	gwas
SLC6A4	HGNC:11050	ENSG00000108576	P31645	Sodium-dependent serotonin transporter	gwas
SNRPC	HGNC:11157	ENSG00000124562	P09234	U1 small nuclear ribonucleoprotein C	gwas
SORT1	HGNC:11186	ENSG00000134243	Q99523	Sortilin	gwas
STAT3	HGNC:11364	ENSG00000168610	P40763	Signal transducer and activator of transcription 3	gwas
TBX20	HGNC:11598	ENSG00000164532	Q9UMR3	T-box transcription factor TBX20	gwas
TBXAS1	HGNC:11609	ENSG00000059377	P24557	Thromboxane-A synthase	gwas
HNF1A	HGNC:11621	ENSG00000135100	P20823	Hepatocyte nuclear factor 1-alpha	gwas
TDRKH	HGNC:11713	ENSG00000182134	Q9Y2W6	Tudor and KH domain-containing protein	gwas
TMOD4	HGNC:11874	ENSG00000163157	Q9NZQ9	Tropomodulin-4	gwas
GIGYF2	HGNC:11960	ENSG00000204120	Q6Y7W6	GRB10-interacting GYF protein 2	gwas
TNS1	HGNC:11973	ENSG00000079308	Q9HBL0	Tensin-1	gwas
UNC5C	HGNC:12569	ENSG00000182168	O95185	Netrin receptor UNC5C	gwas
VAMP5	HGNC:12646	ENSG00000168899	O95183	Vesicle-associated membrane protein 5	gwas
VAMP8	HGNC:12647	ENSG00000118640	Q9BV40	Vesicle-associated membrane protein 8	gwas
VEGFA	HGNC:12680	ENSG00000112715	P15692	Vascular endothelial growth factor A, long form	gwas
VPS33B	HGNC:12712	ENSG00000184056	Q9H267	Vacuolar protein sorting-associated protein 33B	gwas
ZPR1	HGNC:13051	ENSG00000109917	O75312	Zinc finger protein ZPR1	gwas
ZNF77	HGNC:13150	ENSG00000175691	Q15935	Zinc finger protein 77	gwas
FIGN	HGNC:13285	ENSG00000182263	Q5HY92	Fidgetin	gwas
SLC38A1	HGNC:13447	ENSG00000111371	Q9H2H9	Sodium-coupled neutral amino acid symporter 1	gwas
TLNRD1	HGNC:13519	ENSG00000140406	Q9H1K6	Talin rod domain-containing protein 1	gwas
CA10	HGNC:1369	ENSG00000154975	Q9NS85	Carbonic anhydrase-related protein 10	gwas
PRDM16	HGNC:14000	ENSG00000142611	Q9HAZ2	Histone-lysine N-methyltransferase PRDM16	gwas
MRPS6	HGNC:14051	ENSG00000243927	P82932	Small ribosomal subunit protein bS6m	gwas
HDAC4	HGNC:14063	ENSG00000068024	P56524	Histone deacetylase 4	gwas
HDAC9	HGNC:14065	ENSG00000048052	Q9UKV0	Histone deacetylase 9	gwas
WDR12	HGNC:14098	ENSG00000138442	Q9GZL7	Ribosome biogenesis protein WDR12	gwas
PMEPA1	HGNC:14107	ENSG00000124225	Q969W9	Protein TMEPAI	gwas
DOCK9	HGNC:14132	ENSG00000088387	Q9BZ29	Dedicator of cytokinesis protein 9	gwas
RSPH6A	HGNC:14241	ENSG00000104941	Q9H0K4	Radial spoke head protein 6 homolog A	gwas
BCAS3	HGNC:14347	ENSG00000141376	Q9H6U6	BCAS3 microtubule associated cell migration factor	gwas
PAPPA2	HGNC:14615	ENSG00000116183	Q9BXP8	Pappalysin-2	gwas
ZEB2	HGNC:14881	ENSG00000169554	O60315	Zinc finger E-box-binding homeobox 2	gwas
OR52E4	HGNC:15213	ENSG00000180974	Q8NGH9	Olfactory receptor 52E4	gwas
SERPINH1	HGNC:1546	ENSG00000149257	P50454	Serpin H1	gwas
NCKIPSD	HGNC:15486	ENSG00000213672	Q9NZQ3	NCK-interacting protein with SH3 domain	gwas
IL1F10	HGNC:15552	ENSG00000136697	Q8WWZ1	Interleukin-1 family member 10	gwas
CTTNBP2	HGNC:15679	ENSG00000077063	Q8WZ74	Cortactin-binding protein 2	gwas
ZNF335	HGNC:15807	ENSG00000198026	Q9H4Z2	Zinc finger protein 335	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RNF13	E3 ubiquitin-protein ligase RNF13	E3 ubiquitin-protein ligase that regulates cell proliferation.
CNNM2	Metal transporter CNNM2	Divalent metal cation transporter.
ATXN2	Ataxin-2	Involved in EGFR trafficking, acting as negative regulator of endocytic EGFR internalization at the plasma membrane.
BMP1	Bone morphogenetic protein 1	Metalloprotease that plays key roles in regulating the formation of the extracellular matrix (ECM) via processing of various precursor proteins into mature functional enzymes or structural proteins.
CXCL12	Stromal cell-derived factor 1	Chemoattractant active on T-lymphocytes and monocytes but not neutrophils.
SEC24D	Protein transport protein Sec24D	Component of the coat protein complex II (COPII) which promotes the formation of transport vesicles from the endoplasmic reticulum (ER).
SF3A2	Splicing factor 3A subunit 2	Component of the 17S U2 SnRNP complex of the spliceosome, a large ribonucleoprotein complex that removes introns from transcribed pre-mRNAs.
SKI	Ski oncogene	May play a role in terminal differentiation of skeletal muscle cells but not in the determination of cells to the myogenic lineage.
SLC22A4	Solute carrier family 22 member 4	Transporter that mediates the transport of endogenous and microbial zwitterions and organic cations.
BRAP	BRCA1-associated protein	Negatively regulates MAP kinase activation by limiting the formation of Raf/MEK complexes probably by inactivation of the KSR1 scaffold protein.
SLC5A3	Sodium/myo-inositol cotransporter	Electrogenic Na(+)-coupled sugar symporter that actively transports myo-inositol and its stereoisomer scyllo-inositol across the plasma membrane, with a Na(+) to sugar coupling ratio of 2:1.
SLC6A4	Sodium-dependent serotonin transporter	Serotonin transporter that cotransports serotonin with one Na(+) ion in exchange for one K(+) ion and possibly one proton in an overall electroneutral transport cycle.
SNRPC	U1 small nuclear ribonucleoprotein C	Component of the spliceosomal U1 snRNP, which is essential for recognition of the pre-mRNA 5’ splice-site and the subsequent assembly of the spliceosome.
SORT1	Sortilin	Functions as a sorting receptor in the Golgi compartment and as a clearance receptor on the cell surface.
STAT3	Signal transducer and activator of transcription 3	Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors.
TBX20	T-box transcription factor TBX20	Acts as a transcriptional activator and repressor required for cardiac development and may have key roles in the maintenance of functional and structural phenotypes in adult heart.
TBXAS1	Thromboxane-A synthase	Catalyzes the conversion of prostaglandin H2 (PGH2) to thromboxane A2 (TXA2), a potent inducer of blood vessel constriction and platelet aggregation.
HNF1A	Hepatocyte nuclear factor 1-alpha	Transcriptional activator that regulates the tissue specific expression of multiple genes, especially in pancreatic islet cells and in liver.
TDRKH	Tudor and KH domain-containing protein	Participates in the primary piRNA biogenesis pathway and is required during spermatogenesis to repress transposable elements and prevent their mobilization, which is essential for the germline integrity.
TMOD4	Tropomodulin-4	Blocks the elongation and depolymerization of the actin filaments at the pointed end.
GIGYF2	GRB10-interacting GYF protein 2	Key component of the 4EHP-GYF2 complex, a multiprotein complex that acts as a repressor of translation initiation.
TNS1	Tensin-1	May act as a protein phosphatase and/or a lipid phosphatase.
UNC5C	Netrin receptor UNC5C	Receptor for netrin required for axon guidance.
VAMP5	Vesicle-associated membrane protein 5	May participate in trafficking events that are associated with myogenesis, such as myoblast fusion and/or GLUT4 trafficking.
VAMP8	Vesicle-associated membrane protein 8	SNAREs, soluble N-ethylmaleimide-sensitive factor-attachment protein receptors, are essential proteins for fusion of cellular membranes.
VEGFA	Vascular endothelial growth factor A, long form	Participates in the induction of key genes involved in the response to hypoxia and in the induction of angiogenesis such as HIF1A.
VPS33B	Vacuolar protein sorting-associated protein 33B	May play a role in vesicle-mediated protein trafficking to lysosomal compartments and in membrane docking/fusion reactions of late endosomes/lysosomes.
ZPR1	Zinc finger protein ZPR1	Acts as a signaling molecule that communicates proliferative growth signals from the cytoplasm to the nucleus.
ZNF77	Zinc finger protein 77	May be involved in transcriptional regulation.
FIGN	Fidgetin	ATP-dependent microtubule severing protein.
SLC38A1	Sodium-coupled neutral amino acid symporter 1	Symporter that cotransports short-chain neutral amino acids and sodium ions from the extracellular to the intracellular side of the cell membrane.
TLNRD1	Talin rod domain-containing protein 1	Actin-binding protein which may have an oncogenic function and regulates cell proliferation, migration and invasion in cancer cells.
CA10	Carbonic anhydrase-related protein 10	Does not have a catalytic activity.
PRDM16	Histone-lysine N-methyltransferase PRDM16	Transcription regulator that acts both as a histone methyltransferase or chromatin adapter, depending on the context.
HDAC4	Histone deacetylase 4	Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4).
HDAC9	Histone deacetylase 9	Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4).
WDR12	Ribosome biogenesis protein WDR12	Component of the PeBoW complex, which is required for maturation of 28S and 5.8S ribosomal RNAs and formation of the 60S ribosome.
PMEPA1	Protein TMEPAI	Functions as a negative regulator of TGF-beta signaling and thereby probably plays a role in cell proliferation, differentiation, apoptosis, motility, extracellular matrix production and immunosuppression.
DOCK9	Dedicator of cytokinesis protein 9	Guanine nucleotide-exchange factor (GEF) that activates CDC42 by exchanging bound GDP for free GTP.
RSPH6A	Radial spoke head protein 6 homolog A	Functions as part of radial spoke complexes in the axoneme of sperm flagella that play an important part in motility.
BCAS3	BCAS3 microtubule associated cell migration factor	Plays a role in angiogenesis.
PAPPA2	Pappalysin-2	Metalloproteinase which specifically cleaves insulin-like growth factor binding protein (IGFBP)-5 at the ‘163-Ser-|-Lys-164’ bond.
ZEB2	Zinc finger E-box-binding homeobox 2	Transcriptional inhibitor that binds to DNA sequence 5’-CACCT-3’ in different promoters.
OR52E4	Olfactory receptor 52E4	Odorant receptor.
SERPINH1	Serpin H1	Binds specifically to collagen.
NCKIPSD	NCK-interacting protein with SH3 domain	Has an important role in stress fiber formation induced by active diaphanous protein homolog 1 (DRF1).
IL1F10	Interleukin-1 family member 10	Cytokine with immunomodulatory activity.
CTTNBP2	Cortactin-binding protein 2	Regulates the dendritic spine distribution of CTTN/cortactin in hippocampal neurons, and thus controls dendritic spinogenesis and dendritic spine maintenance.
ZNF335	Zinc finger protein 335	Component or associated component of some histone methyltransferase complexes may regulate transcription through recruitment of those complexes on gene promoters.
ZHX3	Zinc fingers and homeoboxes protein 3	Acts as a transcriptional repressor.

Protein-family classification

Druggable: 10 · Difficult: 32 · Unknown: 33 · Druggable fraction: 0.13

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
Scaffold/PPI	13	3.0×	0.003
Transcription factor	19	2.1×	0.006
Phosphatase	1	1.1×	0.989
Transporter	1	1.0×	0.989
Protease	2	1.0×	0.989
Other/Unknown	33	0.8×	0.989
GPCR	2	0.6×	0.989
Antibody/Immunoglobulin	1	0.4×	0.989
Kinase	1	0.4×	0.989
Enzyme (other)	2	0.3×	0.989

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RNF13	Transcription factor	no		Znf_RING, PA_domain, Znf_RING/FYVE/PHD
CNNM2	Other/Unknown	no		CBS_dom, CNNM, RmlC-like_jellyroll
ATXN2	Other/Unknown	no		LsmAD_domain, PAM2_motif, LSM_dom_sf
BMP1	Protease	yes	2.7.11.4	EGF-type_Asp/Asn_hydroxyl_site, EGF, CUB_dom
CXCL12	Other/Unknown	no		Chemokine_IL8-like_dom, CXC_Chemokine_domain, Interleukin_8-like_sf
SEC24D	Transcription factor	no		Znf_Sec23_Sec24, Sec23/24_trunk_dom, Sec23/24_helical_dom
SF3A2	Transcription factor	no		Matrin/U1-C_Znf_C2H2, Matrin/U1-like-C_Znf_C2H2, Znf_C2H2_type
SKI	Other/Unknown	no		SKI/SNO/DAC, DNA-bd_dom_put_sf, SAND-like_dom_sf
SLC22A4	Transporter	yes		Orgcat_transp/SVOP, MFS_sugar_transport-like, Sugar_transporter_CS
BRAP	Transcription factor	no		Znf_UBP, Znf_RING, BRAP2/ETP1_RRM
SLC5A3	Other/Unknown	no		Na/solute_symporter, Na/solute_symporter_CS, Na/Glc_symporter_sf
SLC6A4	Other/Unknown	no		Na/ntran_symport, Na/ntran_symport_serotonin_N, SNS_sf
SNRPC	Transcription factor	no		Matrin/U1-C_Znf_C2H2, Matrin/U1-like-C_Znf_C2H2, U1-CZ_Znf_C2H2
SORT1	Scaffold/PPI	no		VPS10, WD40/YVTN_repeat-like_dom_sf, Sortilin_C
STAT3	Transcription factor	no		SH2, STAT, p53-like_TF_DNA-bd_sf
TBX20	Transcription factor	no		TF_T-box, p53-like_TF_DNA-bd_sf, TF_T-box_CS
TBXAS1	Other/Unknown	no		Cyt_P450, Cyt_P450_E_grp-I, Cyt_P450_CS
HNF1A	Transcription factor	no		HD, HNF1b_C, HNF1a_C
TDRKH	Other/Unknown	no		Tudor, KH_dom, KH_dom_type_1
TMOD4	Other/Unknown	no		TMOD, LRR_dom_sf
GIGYF2	Other/Unknown	no		GYF, GYF-like_dom_sf, GRB10-interact_GYF
TNS1	Phosphatase	yes		SH2, PKC_DAG/PE, Tyr_Pase_cat
UNC5C	Antibody/Immunoglobulin	yes		Death_dom, TSP1_rpt, ZU5_dom
VAMP5	Other/Unknown	no		Synaptobrevin-like, Vamp5, VAMP5_R-SNARE_
VAMP8	Other/Unknown	no		Synaptobrevin-like, Synaptobrevin/VAMP, V_SNARE_CC
VEGFA	Other/Unknown	no		PDGF/VEGF_dom, PD_growth_factor_CS, VEGF_C
VPS33B	Other/Unknown	no		Sec1-like, Sec1-like_dom2, Sec1-like_sf
ZPR1	Transcription factor	no		Znf_ZPR1, ZPR1, ZPR1_A/B_dom
ZNF77	Transcription factor	no		KRAB, Znf_C2H2_type, KRAB_dom_sf
FIGN	Other/Unknown	no		AAA+_ATPase, ATPase_AAA_core, ATPase_AAA_CS
SLC38A1	Other/Unknown	no		AA_transpt_TM
TLNRD1	Other/Unknown	no		TLNRD1, Talin_IBS2B
CA10	Other/Unknown	no		CA_dom, Carbonic_anhydrase_a-class, CA_dom_sf
PRDM16	Transcription factor	no	2.1.1.367	SET_dom, Znf_C2H2_type, Znf_C2H2_sf
MRPS6	Other/Unknown	no		Ribosomal_bS6, Transl_elong_EF1B/ribsomal_bS6, Ribosomal_bS6_sf
HDAC4	Enzyme (other)	yes	3.5.1.98	HDACs, Ureohydrolase_dom_sf, His_deacetylse_dom
HDAC9	Enzyme (other)	yes	3.5.1.98	HDACs, Ureohydrolase_dom_sf, His_deacetylse_dom
WDR12	Scaffold/PPI	no		WD40_rpt, NLE, WD40/YVTN_repeat-like_dom_sf
PMEPA1	Other/Unknown	no		TMEPAI/LRAD4
DOCK9	Scaffold/PPI	no		PH_domain, PH-like_dom_sf, ARM-type_fold
RSPH6A	Other/Unknown	no		Radial_spoke
BCAS3	Scaffold/PPI	no		WD40/YVTN_repeat-like_dom_sf, BCAS3_dom, WD40_repeat_dom_sf
PAPPA2	Protease	yes		Sushi_SCR_CCP_dom, Notch_dom, LamG-like
ZEB2	Transcription factor	no		HD, Di19_Zn-bd, Homeodomain-like_sf
OR52E4	GPCR	yes		GPCR_Rhodpsn, Olfact_rcpt, GPCR_Rhodpsn_7TM
SERPINH1	Other/Unknown	no		Serpin_fam, Serpin_CS, Serpin_dom
NCKIPSD	Scaffold/PPI	no		SH3_domain, SPIN90/Ldb17_LRD, SPIN90/Ldb17
IL1F10	Other/Unknown	no		IL-1_fam, IL-1RA/IL-36, IL1/FGF
CTTNBP2	Scaffold/PPI	no		Ankyrin_rpt, Cortactin-binding_p2_N, Ankyrin_rpt-contain_sf
ZNF335	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Zinc_finger/UBP_domain

Expression context

Cohort genes with no expression data: 0.

68 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	1
moderate (6-20)	0
broad (>20)	74
unknown	0

Top tissues across cohort

Tissue	Cohort genes
sural nerve	8
right testis	7
calcaneal tendon	6
monocyte	6
colonic epithelium	5
left testis	5
cortical plate	5
corpus callosum	4
secondary oocyte	4
stromal cell of endometrium	4
cerebellar hemisphere	4
right hemisphere of cerebellum	4
tibia	4
oocyte	3
pericardium	3
jejunal mucosa	3
choroid plexus epithelium	3
right lung	3
mononuclear cell	3
primordial germ cell in gonad	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RNF13	295	ubiquitous	marker	corpus callosum, calcaneal tendon, inferior vagus X ganglion
CNNM2	234	ubiquitous	marker	secondary oocyte, oocyte, right adrenal gland
ATXN2	286	ubiquitous	marker	buccal mucosa cell, colonic epithelium, olfactory bulb
BMP1	236	ubiquitous	marker	stromal cell of endometrium, left uterine tube, right adrenal gland cortex
CXCL12	275	ubiquitous	marker	synovial joint, pericardium, mammary duct
SEC24D	263	ubiquitous	marker	stromal cell of endometrium, jejunal mucosa, islet of Langerhans
SF3A2	247	ubiquitous	marker	left testis, left ovary, right testis
SKI	268	ubiquitous	marker	nipple, right hemisphere of cerebellum, cerebellar hemisphere
SLC22A4	201	ubiquitous	marker	bronchial epithelial cell, epithelium of bronchus, bronchus
BRAP	286	ubiquitous	marker	left testis, right testis, testis
SLC5A3	291	ubiquitous	marker	renal medulla, choroid plexus epithelium, tibia
SLC6A4	162	tissue_specific	marker	right lung, jejunal mucosa, ileal mucosa
SNRPC	290	ubiquitous	marker	apex of heart, left testis, right testis
SORT1	291	ubiquitous	marker	inferior vagus X ganglion, corpus epididymis, subthalamic nucleus
STAT3	301	ubiquitous	marker	type B pancreatic cell, pericardium, lower lobe of lung
TBX20	52	broad	marker	right atrium auricular region, cardiac atrium, heart
TBXAS1	180	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
HNF1A	81	tissue_specific	yes	right lobe of liver, mucosa of transverse colon, liver
TDRKH	194	ubiquitous	marker	primordial germ cell in gonad, right testis, left testis
TMOD4	176	tissue_specific	yes	vastus lateralis, quadriceps femoris, skeletal muscle tissue of rectus abdominis
GIGYF2	291	ubiquitous	marker	calcaneal tendon, sural nerve, colonic epithelium
TNS1	289	ubiquitous	marker	blood vessel layer, saphenous vein, urethra
UNC5C	202	broad	marker	corpus callosum, tibia, medial globus pallidus
VAMP5	253	ubiquitous	marker	right lung, hindlimb stylopod muscle, upper lobe of left lung
VAMP8	288	ubiquitous	marker	palpebral conjunctiva, monocyte, mononuclear cell
VEGFA	297	ubiquitous	marker	right lobe of thyroid gland, left lobe of thyroid gland, thyroid gland
VPS33B	277	ubiquitous	yes	pancreatic ductal cell, Brodmann (1909) area 23, middle temporal gyrus
ZPR1	267	ubiquitous	marker	cortical plate, ganglionic eminence, right testis
ZNF77	184	ubiquitous	yes	oocyte, secondary oocyte, primordial germ cell in gonad
FIGN	225	ubiquitous	marker	buccal mucosa cell, dorsal root ganglion, endothelial cell

Protein interactions among cohort

Intra-cohort edges: 22.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
STAT3	10,108
CDKN2A	9,311
SCARB1	5,484
WWP2	4,978
CXCL12	4,892
HDAC4	4,771
WDR12	3,702
SNRPC	3,531
CDKN2B	3,431
MORF4L1	3,380

Intra-cohort edges

A	B	Sources
ANGPTL4	CDKN2A	biogrid_interaction, intact
BMP1	IFITM5	string_interaction
CDC123	TLNRD1	intact
CDH13	CDKN2A	string_interaction
CDH13	SCGB1D1	intact
CDKN2A	CDKN2B	biogrid_interaction
GIGYF2	SNRPC	intact
HDAC4	HDAC9	biogrid_interaction
HNF1A	STAT3	biogrid_interaction
IFITM5	SEC24D	string_interaction
MRPS6	SLC5A3	string_interaction
MRPS6	WDR12	string_interaction
SCARB1	VAMP5	intact
SCGB1D1	SLC38A1	intact
SEC24D	WWP2	intact
SF3A2	SNRPC	biogrid_interaction
SNRPC	WWP2	biogrid_interaction, intact
SORT1	TRIB1	string_interaction
SORT1	VAMP5	intact
STAT3	ZFPM2	intact
TBX20	ZFPM2	string_interaction
VAMP5	VAMP8	string_interaction

Structural data

PDB: 44 · AlphaFold-only: 30 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MRPS6	P82932	77
VEGFA	P15692	56
SF3A2	Q15428	43
CXCL12	P48061	34
SLC6A4	P31645	30
HDAC4	P56524	19
SORT1	Q99523	17
WWP2	O00308	11
MORF4L1	Q9UBU8	11
BMP1	P13497	8
CNNM2	Q9H8M5	7
SEC24D	O94855	6
SNRPC	P09234	6
STAT3	P40763	6
HNF1A	P20823	6
NCKIPSD	Q9NZQ3	6
TDRKH	Q9Y2W6	5
TRIB1	Q96RU8	5
SMG6	Q86US8	5
CDKN2A	P42771	5
SKI	P12755	4
DOCK9	Q9BZ29	4
ANGPTL4	Q9BY76	4
GIGYF2	Q6Y7W6	3
WDR12	Q9GZL7	3
CCR1	P32246	3
PDLIM5	Q96HC4	3
RNF13	O43567	2
VAMP8	Q9BV40	2
TLNRD1	Q9H1K6	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
VPS33B	Q9H267	91.82
SERPINH1	P50454	91.71
TBXAS1	P24557	91.50
CDKN2B	P42772	90.12
SCGB1D1	O95968	89.74
OR52E4	Q8NGH9	88.88
TMOD4	Q9NZQ9	86.28
CA10	Q9NS85	85.65
SLC22A4	Q9H015	85.07
SCARB1	Q8WTV0	84.25
VAMP5	O95183	80.60
ZPR1	O75312	80.11
SLC38A1	Q9H2H9	79.81
UNC5C	O95185	78.72
SLC5A3	P53794	78.65
BRAP	Q7Z569	76.92
RSPH6A	Q9H0K4	68.76
ZNF77	Q15935	68.67
GPSM1	Q86YR5	68.24
TBX20	Q9UMR3	67.87
DAB2IP	Q5VWQ8	65.74
IFITM5	A6NNB3	65.49
BCAS3	Q9H6U6	65.25
FIGN	Q5HY92	62.06
CTTNBP2	Q8WZ74	58.83
PMEPA1	Q969W9	57.03
TNS1	Q9HBL0	53.42
ZNF335	Q9H4Z2	52.13
ZFPM2	Q8WW38	51.93
PDZD2	O15018

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 688. Enrichment computed across 236 evidence-associated genes (151 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 151 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Signaling by PDGF	8	13.4×	8e-05	STAT3, COL4A1, COL4A2, COL6A3, PDGFD, FURIN, PLG, BCAR1
Plasma lipoprotein assembly, remodeling, and clearance	6	9.1×	0.016	ANGPTL4, APOC1, APOE, LDLR, LPA, LPL
Attachment of bacteria to epithelial cells	4	13.2×	0.044	COL4A1, COL4A2, FN1, LAMB2
Plasma lipoprotein remodeling	4	12.6×	0.044	ANGPTL4, APOE, LPA, LPL
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	8	4.6×	0.049	PAPPA2, PCSK9, MIA3, FN1, APOE, LAMB2, SERPINA1, PLG
Serotonin clearance from the synaptic cleft	2	37.8×	0.064	SLC6A4, ALDH2
Anchoring fibril formation	3	15.1×	0.064	BMP1, COL4A1, COL4A2
Laminin interactions	4	10.1×	0.064	COL4A1, COL4A2, ITGA1, LAMB2
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer	4	9.8×	0.064	SKI, CDKN2B, SMAD3, SMAD7
Cargo concentration in the ER	4	8.9×	0.064	SEC24D, MIA3, GOSR2, SERPINA1
Integrin cell surface interactions	6	5.3×	0.064	COL4A1, COL4A2, COL6A3, FN1, ITGA1, PECAM1
SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription	4	8.2×	0.079	CDKN2B, SMAD3, SMAD7, FURIN
Chylomicron clearance	2	30.2×	0.081	APOE, LDLR
Scavenging by Class A Receptors	3	11.9×	0.081	COL4A1, COL4A2, APOE
Assembly of active LPL and LIPC lipase complexes	3	11.9×	0.081	ANGPTL4, LPL, FURIN
Collagen biosynthesis and modifying enzymes	5	5.6×	0.081	BMP1, SERPINH1, COL4A1, COL4A2, COL6A3
Fibronectin matrix formation	3	11.3×	0.084	COL4A1, COL4A2, FN1
Crosslinking of collagen fibrils	3	11.3×	0.084	BMP1, COL4A1, COL4A2
ECM proteoglycans	5	5.0×	0.116	COL4A1, COL4A2, COL6A3, FN1, LAMB2
RAC1 GTPase cycle	8	3.2×	0.116	DOCK9, SWAP70, ARHGAP26, FGD5, PLEKHG1, ARHGAP15, ARHGAP42, KALRN
Plasma lipoprotein clearance	3	9.4×	0.123	APOC1, APOE, LDLR
Post-translational protein phosphorylation	6	4.0×	0.125	PCSK9, MIA3, FN1, APOE, LAMB2, SERPINA1
Neurotransmitter clearance	2	16.8×	0.150	SLC6A4, ALDH2
VEGF binds to VEGFR leading to receptor dimerization	2	16.8×	0.150	VEGFA, FLT1
Synthesis of IP3 and IP4 in the cytosol	3	8.4×	0.150	INPP5B, PLCB2, PLCG2
Integrin signaling	3	8.4×	0.150	CSK, FN1, BCAR1
Downregulation of TGF-beta receptor signaling	3	8.1×	0.150	PMEPA1, SMAD3, SMAD7
RUNX3 regulates p14-ARF	2	15.1×	0.157	HDAC4, CDKN2A
Chylomicron remodeling	2	15.1×	0.157	APOE, LPL
Metabolism of fat-soluble vitamins	3	7.6×	0.157	APOE, LDLR, LPL

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 213 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
very-low-density lipoprotein particle clearance	3	47.5×	0.014	APOC1, APOE, LPL
negative regulation of SMAD protein signal transduction	5	14.1×	0.014	SKI, TBX20, PMEPA1, VEPH1, SMAD7
vasodilation	6	10.3×	0.014	VEGFA, SCARB1, ABCC9, APOE, ITGA1, PECAM1
high-density lipoprotein particle clearance	3	33.9×	0.025	SCARB1, APOE, LDLR
triglyceride homeostasis	5	11.3×	0.025	ANGPTL4, SCARB1, APOC1, APOE, LPL
high-density lipoprotein particle remodeling	4	15.1×	0.031	SCARB1, APOC1, APOE, LPL
triglyceride metabolic process	5	10.4×	0.031	SLC22A4, PCSK9, APOC1, APOE, LPL
regulation of phosphatidylcholine catabolic process	2	79.1×	0.034	SCARB1, LDLR
cardiac chamber formation	2	52.7×	0.035	TBX20, EDNRA
positive regulation of low-density lipoprotein particle receptor catabolic process	2	52.7×	0.035	PCSK9, APOE
low-density lipoprotein particle mediated signaling	2	52.7×	0.035	CDH13, LPL
regulation of ribonuclease activity	2	52.7×	0.035	OAS3, PDE3A
motor neuron migration	3	23.7×	0.035	TBX20, VEGFA, CELSR2
negative regulation of low-density lipoprotein particle clearance	3	21.6×	0.035	PCSK9, CSK, LDLR
positive regulation of positive chemotaxis	3	19.8×	0.035	VEGFA, CDH13, SMAD3
cellular response to toxic substance	3	19.8×	0.035	CDH13, EDNRA, TRPA1
artery morphogenesis	4	12.7×	0.035	VEGFA, APOE, LDLR, SMAD7
positive regulation of endothelial cell migration	6	7.1×	0.035	VEGFA, BCAS3, SCARB1, SASH1, PLPP3, BCAR1
collagen fibril organization	6	6.3×	0.035	BMP1, VPS33B, SERPINH1, COL4A1, COL4A2, ADAMTS7
transforming growth factor beta receptor signaling pathway	7	5.2×	0.035	SKI, STAT3, CDKN2B, SMAD3, SMAD7, SMAD9, FURIN
cholesterol homeostasis	7	5.1×	0.035	HDAC9, SCARB1, PCSK9, APOE, LDLR, LPL, FURIN
response to hypoxia	9	4.0×	0.035	CXCL12, SLC6A4, STAT3, VEGFA, ANGPTL4, EDNRA, ABCC9, SMAD3 (+1 more)
positive regulation of MAPK cascade	10	3.8×	0.035	VEGFA, TRIM5, DAB2IP, JCAD, FGF5, FLT1, IL6R, ITGA1 (+2 more)
negative regulation of cell population proliferation	14	2.8×	0.042	SKI, STAT3, DAB2IP, CDH13, CDKN2A, CDKN2B, CSK, SH2B3 (+6 more)
branching involved in blood vessel morphogenesis	4	9.9×	0.047	TBX20, VEGFA, COL4A1, EDNRA
eye photoreceptor cell differentiation	2	39.6×	0.049	STAT3, PPP2R3A
obsolete positive regulation of nitric oxide mediated signal transduction	2	39.6×	0.049	SCARB1, GUCY1A1
post-embryonic camera-type eye development	2	39.6×	0.049	VEGFA, KLF4
plasma lipoprotein particle remodeling	2	39.6×	0.049	APOC1, FURIN
plasma lipoprotein particle clearance	2	39.6×	0.049	SCARB1, LDLR

Therapeutics

Drugs indicated for this disease

26 approved, 47 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Alteplase	Approved (phase 4)
Aspirin	Approved (phase 4)
Atenolol	Approved (phase 4)
Candesartan Cilexetil	Approved (phase 4)
Cangrelor	Approved (phase 4)
Captopril	Approved (phase 4)
Carvedilol	Approved (phase 4)
Enoxaparin Sodium	Approved (phase 4)
Eplerenone	Approved (phase 4)
Eptifibatide	Approved (phase 4)
Evolocumab	Approved (phase 4)
Hydrochlorothiazide	Approved (phase 4)
Nadolol	Approved (phase 4)
Niacin	Approved (phase 4)
Nitroglycerin	Approved (phase 4)
Olmesartan Medoxomil	Approved (phase 4)
Ramipril	Approved (phase 4)
Reteplase	Approved (phase 4)
Simvastatin	Approved (phase 4)
Spironolactone	Approved (phase 4)
Telmisartan	Approved (phase 4)
Tenecteplase	Approved (phase 4)
Ticagrelor	Approved (phase 4)
Torsemide	Approved (phase 4)
Trandolapril	Approved (phase 4)
Valsartan	Approved (phase 4)
Abciximab	Phase 3 (in late-stage trials)
Acetylcysteine	Phase 3 (in late-stage trials)
Adenosine	Phase 3 (in late-stage trials)
Aliskiren	Phase 3 (in late-stage trials)
Amiodarone	Phase 3 (in late-stage trials)
Amlodipine	Phase 3 (in late-stage trials)
Azithromycin	Phase 3 (in late-stage trials)
Bivalirudin	Phase 3 (in late-stage trials)
Chlorthalidone	Phase 3 (in late-stage trials)
Cholestyramine	Phase 3 (in late-stage trials)
Clofibrate	Phase 3 (in late-stage trials)
Clopidogrel	Phase 3 (in late-stage trials)
Colchicine	Phase 3 (in late-stage trials)
Cyclosporine	Phase 3 (in late-stage trials)
Darbepoetin Alfa	Phase 3 (in late-stage trials)
Dextrose	Phase 3 (in late-stage trials)
Doxazosin	Phase 3 (in late-stage trials)
Empagliflozin	Phase 3 (in late-stage trials)
Epoetin Beta	Phase 3 (in late-stage trials)
Estrogens, Conjugated	Phase 3 (in late-stage trials)
Exenatide	Phase 3 (in late-stage trials)
Ezetimibe	Phase 3 (in late-stage trials)
Filgrastim	Phase 3 (in late-stage trials)
Heparin	Phase 3 (in late-stage trials)
Hyaluronidase	Phase 3 (in late-stage trials)
Imipramine	Phase 3 (in late-stage trials)
Insulin Human	Phase 3 (in late-stage trials)
Lisinopril Anhydrous	Phase 3 (in late-stage trials)
Metoprolol	Phase 3 (in late-stage trials)
Mexiletine	Phase 3 (in late-stage trials)
Nicorandil	Phase 3 (in late-stage trials)
OMEGA-3-ACID ETHYL ESTERS	Phase 3 (in late-stage trials)
Potassium Chloride	Phase 3 (in late-stage trials)
Prasugrel	Phase 3 (in late-stage trials)
Pravastatin	Phase 3 (in late-stage trials)
Procainamide	Phase 3 (in late-stage trials)
Propafenone	Phase 3 (in late-stage trials)
Propranolol	Phase 3 (in late-stage trials)
Quinidine	Phase 3 (in late-stage trials)
Rivaroxaban	Phase 3 (in late-stage trials)
Sacubitril	Phase 3 (in late-stage trials)
Sodium Chloride	Phase 3 (in late-stage trials)
Sotalol	Phase 3 (in late-stage trials)
Streptokinase	Phase 3 (in late-stage trials)
Tirofiban	Phase 3 (in late-stage trials)
Vitamin E	Phase 3 (in late-stage trials)
Warfarin	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Ascorbic Acid, Atorvastatin, Balixafortide, Beta Carotene, Cyanocobalamin, Dapagliflozin, Epoetin Alfa, Firibastat, Folic Acid, Goflikicept, Hydrocortisone, Inclacumab, Mangafodipir, Methotrexate, Nesiritide, Nitroprusside, Oxytocin, Paroxetine, Perflutren, Pyridoxine, Riboflavin, Rosuvastatin.

Drug target analysis

Approved (phase 4): 8 · Phase ≥3: 9 · Phased (≥1): 10 · Undrugged: 65

Druggability breadth: 84 of 236 evidence-associated genes (36%) 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
CXCL12	PLERIXAFOR
SLC6A4	CETIRIZINE
STAT3	MOMELOTINIB
TBXAS1	CLOTRIMAZOLE
VEGFA	VADADUSTAT
HDAC4	CELECOXIB
HDAC9	CELECOXIB
CCR1	ABAMETAPIR

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SLC6A4	422	4
TBXAS1	46	4
HDAC4	31	4
HDAC9	28	4
STAT3	18	4
CCR1	8	4
VEGFA	5	4
CXCL12	2	4
SCARB1	2	2
SORT1	1	3

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PLERIXAFOR	4	CXCL12
DIFLUNISAL	4	CXCL12
CETIRIZINE	4	SLC6A4
BEPRIDIL	4	SLC6A4
CLOTRIMAZOLE	4	SLC6A4, TBXAS1
ACETOPHENAZINE	4	SLC6A4
NIRAPARIB	4	SLC6A4
INDACATEROL	4	SLC6A4
IMIPRAMINE	4	SLC6A4
EPINASTINE	4	SLC6A4
ARIPIPRAZOLE	4	SLC6A4
AMOXAPINE	4	SLC6A4
IDARUBICIN	4	SLC6A4
DESVENLAFAXINE	4	SLC6A4
NORETHINDRONE	4	SLC6A4
PONATINIB	4	SLC6A4
DESLORATADINE	4	SLC6A4
DULOXETINE	4	SLC6A4
CELECOXIB	4	HDAC4, HDAC9, SLC6A4
UMECLIDINIUM	4	SLC6A4
PALONOSETRON	4	SLC6A4
PHENIRAMINE	4	SLC6A4
VILANTEROL	4	SLC6A4
ESCITALOPRAM OXALATE	4	SLC6A4
TIOCONAZOLE	4	SLC6A4
NEFAZODONE HYDROCHLORIDE	4	SLC6A4
ETHYLESTRENOL	4	SLC6A4
CALCIPOTRIENE	4	SLC6A4
CINACALCET HYDROCHLORIDE	4	SLC6A4
CITALOPRAM HYDROBROMIDE	4	SLC6A4

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 6.

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

Symbol	Assays	Type breakdown
HDAC4	1,941	Binding:1919, ADMET:13, Functional:6, Toxicity:3
HDAC9	1,625	Binding:1612, ADMET:8, Functional:4, Toxicity:1
STAT3	1,319	Binding:1304, Functional:12, Unclassified:2, ADMET:1
SLC6A4	1,055	Binding:1021, Functional:18, ADMET:9, Toxicity:6, Unclassified:1
CCR1	243	Binding:176, Functional:67
TBXAS1	210	Binding:138, Functional:72
VEGFA	64	Binding:64
BMP1	30	Binding:29, ADMET:1
CXCL12	29	Binding:29
SLC22A4	29	Functional:26, ADMET:3
SORT1	17	Binding:15, ADMET:2
DAB2IP	8	Binding:8
SF3A2	7	Binding:7
ATXN2	5	Binding:3, Functional:2
GIGYF2	5	Binding:5
WDR12	5	Binding:5
SCARB1	4	Binding:4
BRAP	2	Binding:2
SLC38A1	2	Binding:2
PRDM16	2	Binding:2
MORF4L1	2	Binding:2
CDKN2A	2	Binding:2
HNF1A	1	Binding:1
VAMP8	1	Binding:1
SERPINH1	1	Binding:1
TRIB1	1	Binding:1
PDLIM5	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BMP1	2.7.11.4, 3.4.24.19, 3.4.24.21	[3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] kinase, procollagen C-endopeptidase, astacin
PRDM16	2.1.1.367, 2.1.1.370	[histone H3]-lysine9 N-methyltransferase, [histone H3]-lysine4 N-dimethyltransferase
HDAC4	3.5.1.98	histone deacetylase
HDAC9	3.5.1.98	histone deacetylase
TRIM5	2.3.2.27	RING-type E3 ubiquitin transferase
WWP2	2.3.2.26	HECT-type E3 ubiquitin transferase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
SLC6A4	1,055
STAT3	1,319
TBXAS1	210
HDAC4	1,941
HDAC9	1,625
CCR1	243

Pharmacogenomics

Cohort genes with a PharmGKB record: 75; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
SLC6A4	1

Chemical tractability of cohort targets

30 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)
PLERIXAFOR	4	CXCL12
DIFLUNISAL	4	CXCL12
CETIRIZINE	4	SLC6A4
BEPRIDIL	4	SLC6A4
CLOTRIMAZOLE	4	SLC6A4, TBXAS1
ACETOPHENAZINE	4	SLC6A4
NIRAPARIB	4	SLC6A4
INDACATEROL	4	SLC6A4
IMIPRAMINE	4	SLC6A4
EPINASTINE	4	SLC6A4
ARIPIPRAZOLE	4	SLC6A4
AMOXAPINE	4	SLC6A4
IDARUBICIN	4	SLC6A4
DESVENLAFAXINE	4	SLC6A4
NORETHINDRONE	4	SLC6A4
PONATINIB	4	SLC6A4
DESLORATADINE	4	SLC6A4
DULOXETINE	4	SLC6A4
CELECOXIB	4	HDAC4, HDAC9, SLC6A4
UMECLIDINIUM	4	SLC6A4
PALONOSETRON	4	SLC6A4
PHENIRAMINE	4	SLC6A4
VILANTEROL	4	SLC6A4
ESCITALOPRAM OXALATE	4	SLC6A4
TIOCONAZOLE	4	SLC6A4
NEFAZODONE HYDROCHLORIDE	4	SLC6A4
ETHYLESTRENOL	4	SLC6A4
CALCIPOTRIENE	4	SLC6A4
CINACALCET HYDROCHLORIDE	4	SLC6A4
CITALOPRAM HYDROBROMIDE	4	SLC6A4

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	8	CXCL12, SLC6A4, STAT3, TBXAS1, VEGFA, HDAC4, HDAC9, CCR1
B	Phased (≥1) drug, not yet approved	2	SORT1, SCARB1
C	Druggable family + PDB, no drug	3	BMP1, PAPPA2, TRIB1
D	Druggable family + AlphaFold only, no drug	4	SLC22A4, TNS1, UNC5C, OR52E4
E	Difficult family or no structure, no drug	58	RNF13, CNNM2, ATXN2, SEC24D, SF3A2, SKI, BRAP, SLC5A3, SNRPC, TBX20 (+48 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
RNF13	0	—
CNNM2	0	—
ATXN2	5	—
BMP1	30	—
SEC24D	0	—
SF3A2	7	—
SKI	0	—
SLC22A4	29	—
BRAP	2	—
SLC5A3	0	—
SNRPC	0	—
TBX20	0	—
HNF1A	1	—
TDRKH	0	—
TMOD4	0	—
GIGYF2	5	—
TNS1	0	—
UNC5C	0	—
VAMP5	0	—
VAMP8	1	—
VPS33B	0	—
ZPR1	0	—
ZNF77	0	—
FIGN	0	—
SLC38A1	2	—
TLNRD1	0	—
CA10	0	—
PRDM16	2	—
MRPS6	0	—
WDR12	5	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1,384.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	656
PHASE4	163
PHASE3	132
PHASE2	72
PHASE1/PHASE2	28
PHASE2/PHASE3	22
PHASE1	22
EARLY_PHASE1	5

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04416581	PHASE4	RECRUITING	Potassium-Competitive Acid Blocker Versus pROton-Pump Inhibitor for GastroproTECTion Strategies In Patients at High Gastro-Intestinal Bleeding Risk Receiving Antithrombotic Therapy
NCT04436978	PHASE4	RECRUITING	What is the Optimal Antithrombotic Strategy in Patients With Atrial Fibrillation Undergoing PCI?
NCT04499859	PHASE4	RECRUITING	Low Dose Rosuvastatin Plus Ezetimibe Versus High-dose Rosuvastatin in AMI
NCT04769362	PHASE4	RECRUITING	Long-term Beta-blocker Therapy After Acute Myocardial Infarction
NCT05168462	PHASE4	RECRUITING	Clinical Outcome and Cost-effectiveness of Reduced Noradrenaline by Using a Lower Blood Pressure Target in Patients With Cardiogenic Shock From Acute Myocardial Infarction
NCT05262803	PHASE4	RECRUITING	Reduced Antithrombotic Strategy for High Bleeding Risk Patients With Myocardial Infarction
NCT05284747	PHASE4	ACTIVE_NOT_RECRUITING	EVOLVE-MI: EVOLocumab Very Early After Myocardial Infarction
NCT05794399	PHASE4	RECRUITING	Anticoagulation in Post MI LV Thrombus Trial in Nepal
NCT06562582	PHASE4	RECRUITING	STunning in Acute Myocardial Infarction - BAS
NCT07203846	PHASE4	NOT_YET_RECRUITING	Modulation of Gut MicroFLORA With Rifaximin to Reduce High Platelet Reactivity in Post-ACS Patients on Ticagrelor
NCT07507500	PHASE4	NOT_YET_RECRUITING	Dual Antiplatelet Therapy Strategies After Acute Myocardial Infarction Undergoing PCI: Prasugrel vs Ticagrelor & 12 Months vs 1-3 Months
NCT07549282	PHASE4	NOT_YET_RECRUITING	Use Dexmedetomidine To Protect Myocardial Injury Evaluation
NCT00025766	PHASE4	COMPLETED	Angioplasty and Heart Stents to Treat Individuals With an Occluded Artery Following a Heart Attack
NCT00106886	PHASE4	UNKNOWN	HOPE-2 Study (Heart Outcomes Prevention Evaluation-2 Study)
NCT00111566	PHASE4	COMPLETED	BRIEF-PCI: Brief Infusion of Eptifibatide Following Percutaneous Coronary Intervention
NCT00125645	PHASE4	COMPLETED	Left Ventricular Function After Acute Myocardial Infarction (AMI). Treatment With Angiotensin 2-Receptor Blockade (GLOBAL-Study)
NCT00126100	PHASE4	COMPLETED	Bone Marrow Stem Cell Mobilisation Therapy for Acute Myocardial Infarction (AMI)(REVIVAL-2)
NCT00126334	PHASE4	COMPLETED	Conservative Versus Liberal Red Cell Transfusion in Myocardial Infarction Trial: The CRIT Pilot
NCT00128024	PHASE4	COMPLETED	Effects of Early Statin Treatment After Acute Myocardial Infarction (AMI) in Japanese Patients
NCT00128791	PHASE4	TERMINATED	Nitroprusside for Prevention of no-Reflow in Primary Angioplasty
NCT00132093	PHASE4	COMPLETED	Effects of Eplerenone on Left Ventricular Remodelling Following Heart Attack
NCT00133250	PHASE4	COMPLETED	Value of Abciximab in Patients With AMI Undergoing Primary PCI After Clopidogrel Pretreatment (BRAVE 3)
NCT00138034	PHASE4	COMPLETED	APRICOT-3: Antithrombotics in the Prevention of Reocclusion In COronary Thrombolysis -3
NCT00162331	PHASE4	COMPLETED	CARDIOLITE-413: A Study for Patients Who Had a PCI for an Acute MI
NCT00168792	PHASE4	TERMINATED	A Trial Evaluating the Efficacy and Safety of Tenecteplase Together With Unfractionated Heparin Prior to Early Percutaneous Coronary Intervention (PCI) as Compared to Standard Primary PCI in Patients With Acute Myocardial Infarction (ASSENT 4 PCI)
NCT00171275	PHASE4	COMPLETED	Fluvastatin in the Therapy of Acute Coronary Syndrome
NCT00178620	PHASE4	COMPLETED	Pre-hospital Administration of Thrombolytic Therapy With Urgent Culprit Artery Revascularization
NCT00181818	PHASE4	COMPLETED	Bupropion for Hospitalized Smokers With Acute Cardiovascular Disease
NCT00212004	PHASE4	TERMINATED	Pioglitazone Protects Diabetes Mellitus (DM) Patients Against Re-Infarction (PPAR Study)
NCT00229515	PHASE4	UNKNOWN	Multicentre 2x2 Factorial Randomised Study Comparing Tirofiban Versus Abciximab and SES Versus BMS in AMI
NCT00237471	PHASE4	TERMINATED	Impact of Tight Glycaemic Control in Acute Myocardial Infarction
NCT00263393	PHASE4	COMPLETED	Rural Andhra Pradesh Cardiovascular Prevention Study (RAPCAPS)
NCT00265239	PHASE4	COMPLETED	Pilot Study of Edaravone to Treat Acute Myocardial Infarction
NCT00272337	PHASE4	COMPLETED	Aspirin Dose and Atherosclerosis in Patients With Heart Disease
NCT00275990	PHASE4	COMPLETED	AngioJET Thrombectomy and STENTing for Treatment of Acute Myocardial Infarction
NCT00286312	PHASE4	COMPLETED	Myocardial Infarction Size Reduction With Atorvastatin
NCT00288210	PHASE4	UNKNOWN	Sirolimus Eluting Stenting in Acute Myocardial Infarction
NCT00306228	PHASE4	COMPLETED	Role of Tirofiban and the Paclitaxel Eluting Stent in Postfibrinolysis Angioplasty
NCT00314847	PHASE4	TERMINATED	Comparison of Standard Treatment Versus Standard Treatment Plus Extracorporeal Life Support (ECLS) in Myocardial Infarction Complicated With Cardiogenic Shock
NCT00320229	PHASE4	TERMINATED	Half-Dose Intracoronary Abciximab Bolus Improves the Mortality Outcome Compared to Standard Intravenous Regimen

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ABCIXIMAB	4	12
CLOPIDOGREL	4	12
PRASUGREL	4	10
TENECTEPLASE	4	9
TICAGRELOR	4	9
HEPARIN	4	6
RAMIPRIL	4	4
TIROFIBAN	4	4
ATORVASTATIN	4	3
BIVALIRUDIN	4	3
SIMVASTATIN	4	3
ASPIRIN	4	2
CILOSTAZOL	4	2
EPLERENONE	4	2
EPTIFIBATIDE	4	2
EXENATIDE	4	2
NITROPRUSSIDE	4	2
ATENOLOL	4	1
CARVEDILOL	4	1
EDARAVONE	4	1
ETANERCEPT	4	1
FLUVASTATIN	4	1
HYDROCHLOROTHIAZIDE	4	1
INSULIN HUMAN	4	1
IRBESARTAN	4	1
MORPHINE	4	1
PACLITAXEL	4	1
PIOGLITAZONE	4	1
RETEPLASE	4	1
SITAGLIPTIN	4	1