API5

Summary

API5 (apoptosis inhibitor 5, HGNC:594) is a protein-coding gene on chromosome 11p12, encoding Apoptosis inhibitor 5 (Q9BZZ5). Antiapoptotic factor that may have a role in protein assembly.

This gene encodes an apoptosis inhibitory protein whose expression prevents apoptosis after growth factor deprivation. This protein suppresses the transcription factor E2F1-induced apoptosis and also interacts with, and negatively regulates Acinus, a nuclear factor involved in apoptotic DNA fragmentation. Its depletion enhances the cytotoxic action of the chemotherapeutic drugs. Multiple alternatively spliced transcript variants encoding different isoforms have been identified.

Source: NCBI Gene 8539 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 40 total
• Druggable target: yes
• MANE Select transcript: NM_001142930

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:594
Approved symbol	API5
Name	apoptosis inhibitor 5
Location	11p12
Locus type	gene with protein product
Status	Approved
Aliases	AAC-11, API5L1, AAC11
Ensembl gene	ENSG00000166181
Ensembl biotype	protein_coding
OMIM	609774
Entrez	8539

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 16 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000378852, ENST00000420461, ENST00000455725, ENST00000526394, ENST00000529334, ENST00000529932, ENST00000530300, ENST00000531273, ENST00000532267, ENST00000534600, ENST00000534695, ENST00000866289, ENST00000866290, ENST00000866291, ENST00000866292, ENST00000866293, ENST00000866294, ENST00000866295, ENST00000931881, ENST00000949751

RefSeq mRNA: 4 — MANE Select: NM_001142930 NM_001142930, NM_001142931, NM_001243747, NM_006595

CCDS: CCDS31465, CCDS44572, CCDS44573

Canonical transcript exons

ENST00000531273 — 14 exons

Exon	Start	End
ENSE00001100637	43326507	43326611
ENSE00001100639	43329965	43330058
ENSE00001100641	43328712	43328893
ENSE00001100645	43320821	43320914
ENSE00001100648	43327789	43327878
ENSE00001100652	43318640	43318801
ENSE00001100659	43321411	43321476
ENSE00001100662	43323430	43323636
ENSE00001100672	43321985	43322136
ENSE00002177230	43342428	43344529
ENSE00003514773	43335278	43335354
ENSE00003628082	43330508	43330564
ENSE00003628769	43335858	43335994
ENSE00003682503	43311996	43312196

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 96.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 79.8873 / max 1152.3094, expressed in 1823 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
113936	79.6226	1823
113937	0.2647	96

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	96.44	gold quality
rectum	UBERON:0001052	96.14	gold quality
ventricular zone	UBERON:0003053	96.10	gold quality
superficial temporal artery	UBERON:0001614	95.94	gold quality
oocyte	CL:0000023	95.82	gold quality
parotid gland	UBERON:0001831	95.71	gold quality
endometrium	UBERON:0001295	95.43	gold quality
ganglionic eminence	UBERON:0004023	95.35	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.25	gold quality
caecum	UBERON:0001153	95.22	gold quality
vermiform appendix	UBERON:0001154	95.17	gold quality
penis	UBERON:0000989	95.16	gold quality
colonic epithelium	UBERON:0000397	95.08	gold quality
cortical plate	UBERON:0005343	95.02	gold quality
calcaneal tendon	UBERON:0003701	95.00	gold quality
lymph node	UBERON:0000029	94.98	gold quality
renal medulla	UBERON:0000362	94.88	gold quality
monocyte	CL:0000576	94.79	gold quality
secondary oocyte	CL:0000655	94.77	gold quality
medial globus pallidus	UBERON:0002477	94.73	gold quality
pylorus	UBERON:0001166	94.71	gold quality
embryo	UBERON:0000922	94.70	gold quality
mononuclear cell	CL:0000842	94.66	gold quality
leukocyte	CL:0000738	94.60	gold quality
germinal epithelium of ovary	UBERON:0001304	94.59	gold quality
globus pallidus	UBERON:0001875	94.58	gold quality
oral cavity	UBERON:0000167	94.54	gold quality
jejunal mucosa	UBERON:0000399	94.53	gold quality
smooth muscle tissue	UBERON:0001135	94.49	gold quality
cauda epididymis	UBERON:0004360	94.48	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.68
E-ENAD-17	no	922.44
E-MTAB-2983	no	415.28

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

174 targeting API5, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-3658	99.96	73.87	4379

Literature-anchored findings (GeneRIF, showing 23)

• Apoptosis inhibitor-5/antiapoptosis clone-11 (Api5/Aac11) is a critical determinant of dE2F1-induced apoptosis in vivo and in vitro. (PMID:17112319)
• define a true in vivo target of miR-224 and reaffirm the important role of miRNAs in the dysregulation of cellular processes that may ultimately lead to tumorigenesis (PMID:18319255)
• The authors report here that AAC-11, a survival protein whose expression prevents apoptosis that occurs on deprivation of growth factors, physiologically binds to Acinus and prevents Acinus-mediated DNA fragmentation. (PMID:19387494)
• we infer that Pim-2 could activate API-5 to inhibit the apoptosis of liver cells, and NF-kappaB is the key regulator (PMID:19821157)
• The prognostic significance of the genes casein kinase 2 alpha subunit (CSNK2A1), anti-apoptosis clone-11 (AAC-11), and tumor metastasis suppressor NME1 in completely resected non-small cell lung cancer (NSCLC) patients, was analysed. (PMID:20671611)
• structure and function of API5 (PMID:22334682)
• Api5, even if not physically interacting with E2F1, contributes positively to E2F1 transcriptional activity by increasing E2F1 binding to its target promoters. (PMID:23940755)
• API5 acts as an immune escape gene in tumors by rendering them resistant to apoptosis triggered by tumor antigen-specific T cells. (PMID:24769442)
• Low miR-224 and high API5 expression correlated with worse survival of glioblastoma patients. (PMID:24785373)
• API5 overexpression promoted cell proliferation and colony formation in CaSki cancer cells, whereas API5 knockdown inhibited the both properties in HeLa cells; API5 expression is associated with pERK1/2 in a subset of cervical cancer patients and its expression predicts poor overall survival. (PMID:25070070)
• Authors show that API5 increases the metastatic capacity of cervical cancer cells in vitro and in vivo via up-regulation of MMP-9. (PMID:25248562)
• Negative regulation of API-5 expression by miR-1 was demonstrated to promote apoptosis of HepG2 cells. (PMID:25433291)
• miR-143 and miR-145 and the predicted target proteins API5, ERK5, K-RAS, and IRS-1 display regional differences in expression in the colon (PMID:25477374)
• rs17684886 (ZNRF1) and rs599019 (COLEC12) are associated with diabetic retinopathy and rs6427247 (SCYL1BP1) and rs899036 (API5) are associated with severe diabetic retinopathy in Chinese patients with type 2 diabetes (PMID:25819896)
• Authors propose a proapoptotic role for NP in IAV pathogenesis, whereby it suppresses expression of antiapoptotic factor API5, thus potentiating the E2F1-dependent apoptotic pathway and ensuring viral replication. (PMID:26673663)
• study demonstrates that apoptosis inhibitor 5 is an endogenous and direct inhibitor of caspase-2. API5 protein directly binds to the caspase recruitment domain (CARD) of caspase-2 and impedes dimerization and activation of caspase-2. (PMID:28336776)
• Regulation of mRNA export through API5 and nuclear FGF2 interaction. (PMID:32383752)
• Evolution and Structure of API5 and Its Roles in Anti-Apoptosis. (PMID:33319655)
• MicroRNA-224 modulates chemosensitivity of breast cancer cells to docetaxel by apoptosis inhibitor 5. (PMID:34076992)
• DeSUMOylation of Apoptosis Inhibitor 5 by Avibirnavirus VP3 Supports Virus Replication. (PMID:34372697)
• Interplay between p300 and HDAC1 regulate acetylation and stability of Api5 to regulate cell proliferation. (PMID:34385547)
• The gammadelta IEL effector API5 masks genetic susceptibility to Paneth cell death. (PMID:36198790)
• Altered expression of anti-apoptotic protein Api5 affects breast tumorigenesis. (PMID:37095445)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	api5	ENSDARG00000033597
mus_musculus	Api5	ENSMUSG00000027193
rattus_norvegicus	Api5	ENSRNOG00000009689
drosophila_melanogaster	cass	FBGN0286781

Protein

Protein identifiers

Apoptosis inhibitor 5 — Q9BZZ5 (reviewed: Q9BZZ5)

Alternative names: Antiapoptosis clone 11 protein, Cell migration-inducing gene 8 protein, Fibroblast growth factor 2-interacting factor, Protein XAGL

All UniProt accessions (3): E9PQK6, Q9BZZ5, H0YER7

UniProt curated annotations — full annotation on UniProt →

Function. Antiapoptotic factor that may have a role in protein assembly. Negatively regulates ACIN1. By binding to ACIN1, it suppresses ACIN1 cleavage from CASP3 and ACIN1-mediated DNA fragmentation. Also known to efficiently suppress E2F1-induced apoptosis. Its depletion enhances the cytotoxic action of the chemotherapeutic drugs.

Subunit / interactions. Monomer. Interacts with FGF2 and ACIN1.

Subcellular location. Nucleus. Cytoplasm Cytoplasm.

Tissue specificity. Expressed in all tissues tested, including heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Highest levels in heart, pancreas and placenta. Highly expressed in several cancers. Preferentially expressed in squamous cell carcinoma versus adenocarcinoma in non-small cell lung cancer.

Post-translational modifications. Acetylation at Lys-251 impairs antiapoptotic function.

Domain organisation. Two regions, an N-terminal (aa 96-107) and a C-terminal (aa 274-311) are required for binding FGF2.

Similarity. Belongs to the API5 family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q9BZZ5-4	4	yes
Q9BZZ5-1	1, FIF-510
Q9BZZ5-2	2, FIF-504
Q9BZZ5-3	3, FIF C1
Q9BZZ5-5	5
Q9BZZ5-6	6

RefSeq proteins (4): NP_001136402, NP_001136403, NP_001230676, NP_006586 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008383	API5	Family
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily

Pfam: PF05918

UniProt features (64 total): helix 32, splice variant 8, modified residue 6, region of interest 3, sequence variant 3, turn 3, strand 3, compositionally biased region 2, initiator methionine 1, chain 1, sequence conflict 1, short sequence motif 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3U0R	X-RAY DIFFRACTION	2.5
3V6A	X-RAY DIFFRACTION	2.6
6L4O	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BZZ5-F1	85.04	0.76

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (6): 462, 464, 469, 500, 251, 399

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 192 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, ENK_UV_RESPONSE_KERATINOCYTE_UP, MORF_SNRP70, AAGCCAT_MIR135A_MIR135B, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, LANG_MYB_FAMILY_TARGETS, GGGCATT_MIR365, CATTTCA_MIR203, AAACCAC_MIR140, LEE_METASTASIS_AND_ALTERNATIVE_SPLICING_DN, GARY_CD5_TARGETS_DN, DOUGLAS_BMI1_TARGETS_DN, AFFAR_YY1_TARGETS_DN, HU_GENOTOXIN_ACTION_DIRECT_VS_INDIRECT_24HR, CTTTGTA_MIR524

GO Biological Process (4): negative regulation of apoptotic process (GO:0043066), fibroblast apoptotic process (GO:0044346), negative regulation of fibroblast apoptotic process (GO:2000270), apoptotic process (GO:0006915)

GO Molecular Function (3): RNA binding (GO:0003723), fibroblast growth factor binding (GO:0017134), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), spliceosomal complex (GO:0005681), cytoplasm (GO:0005737), membrane (GO:0016020), nuclear speck (GO:0016607)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
apoptotic process	2
cellular anatomical structure	2
regulation of apoptotic process	1
negative regulation of programmed cell death	1
negative regulation of apoptotic process	1
fibroblast apoptotic process	1
regulation of fibroblast apoptotic process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
nucleic acid binding	1
growth factor binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1
intracellular anatomical structure	1
nuclear ribonucleoprotein granule	1

Protein interactions and networks

STRING

2174 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
API5	ACIN1	Q9UKV3	623
API5	FGF2	P09038	571
API5	FGF13	Q92913	566
API5	ANKS1A	Q92625	423
API5	CDKN1B	P46527	416
API5	AKT3	Q9Y243	410
API5	QTRT1	Q9BXR0	401
API5	TPSG1	Q9NRR2	399
API5	TMBIM6	P55061	393
API5	FNDC3B	Q53EP0	392
API5	VWCE	Q96DN2	386
API5	CASP2	P42575	383
API5	RPS19	P39019	383
API5	DDX42	Q86XP3	379
API5	AATF	Q9NY61	378

IntAct

69 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
API5	DDX39B	psi-mi:“MI:0915”(physical association)	0.560
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
CPSF6	DDX39A	psi-mi:“MI:0914”(association)	0.480
API5	ACIN1	psi-mi:“MI:0915”(physical association)	0.460
API5	ACIN1	psi-mi:“MI:0403”(colocalization)	0.460
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
API5	SOCS6	psi-mi:“MI:0915”(physical association)	0.400
OSGEPL1	API5	psi-mi:“MI:0915”(physical association)	0.400
FRG2	API5	psi-mi:“MI:0915”(physical association)	0.400
LTV1	API5	psi-mi:“MI:0915”(physical association)	0.400
CEP112	API5	psi-mi:“MI:0915”(physical association)	0.400
H1-9P	API5	psi-mi:“MI:0915”(physical association)	0.400
	AGPS	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
API5	ACIN1	psi-mi:“MI:0915”(physical association)	0.400
ACIN1	API5	psi-mi:“MI:0915”(physical association)	0.400
API5	API5	psi-mi:“MI:0915”(physical association)	0.400
API5	HTT	psi-mi:“MI:0915”(physical association)	0.370
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
ANG	DDX39A	psi-mi:“MI:0914”(association)	0.350
DLD	NFKBIE	psi-mi:“MI:0914”(association)	0.350
SOD1	NPEPPSL1	psi-mi:“MI:0914”(association)	0.350
MAPT	C11orf98	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
DCUN1D1	RGSL1	psi-mi:“MI:0914”(association)	0.350

BioGRID (223): API5 (Affinity Capture-MS), API5 (Co-fractionation), API5 (Co-fractionation), API5 (Co-fractionation), API5 (Co-fractionation), API5 (Co-fractionation), API5 (Co-fractionation), DDX39A (Co-fractionation), EIF6 (Co-fractionation), IMPDH2 (Co-fractionation), OSGEP (Co-fractionation), TBC1D23 (Co-fractionation), TTI1 (Co-fractionation), XRN2 (Co-fractionation), API5 (Affinity Capture-MS)

ESM2 similar proteins: A0MT11, A1Z3X3, A2VD00, A4GWN3, A4II09, A4QNE0, A4VCH4, B5KFI0, O35841, P23116, P49754, Q09161, Q0P5I8, Q14152, Q15006, Q15386, Q1JU68, Q3B8M3, Q5E993, Q5E9L7, Q5KU39, Q5R4J9, Q5R644, Q5R882, Q5RE70, Q5XI83, Q5ZJZ6, Q5ZKG8, Q5ZMW3, Q68E01, Q6GLK9, Q6N069, Q6NRL4, Q6PCR7, Q6TGY8, Q6WKZ8, Q7L5D6, Q7TPD0, Q80UM3, Q8BHL5

Diamond homologs: O35841, Q5R644, Q5ZMW3, Q6DDM4, Q6Z6S1, Q7ZY79, Q9BZZ5, Q9V431, Q54CL0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 74 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
mRNA splicing, via spliceosome	7	10.2×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

40 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	29
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1975 predictions. Top by Δscore:

Variant	Effect	Δscore
11:43312192:GCCAG:G	donor_gain	1.0000
11:43312195:AGG:A	donor_loss	1.0000
11:43312197:G:GG	donor_gain	1.0000
11:43312197:GT:G	donor_loss	1.0000
11:43318633:A:AG	acceptor_gain	1.0000
11:43318634:T:G	acceptor_gain	1.0000
11:43318636:TCA:T	acceptor_loss	1.0000
11:43318638:A:AG	acceptor_gain	1.0000
11:43318638:AGC:A	acceptor_loss	1.0000
11:43318639:G:GA	acceptor_gain	1.0000
11:43318639:GC:G	acceptor_gain	1.0000
11:43318639:GCA:G	acceptor_gain	1.0000
11:43318639:GCAT:G	acceptor_gain	1.0000
11:43318639:GCATA:G	acceptor_gain	1.0000
11:43318797:TATCT:T	donor_gain	1.0000
11:43318798:ATCT:A	donor_gain	1.0000
11:43318798:ATCTG:A	donor_loss	1.0000
11:43318800:CTGT:C	donor_loss	1.0000
11:43318802:G:GG	donor_gain	1.0000
11:43318803:T:TC	donor_loss	1.0000
11:43320806:T:A	acceptor_gain	1.0000
11:43320809:A:AG	acceptor_gain	1.0000
11:43320810:A:AG	acceptor_gain	1.0000
11:43320810:ATCAT:A	acceptor_gain	1.0000
11:43320811:T:G	acceptor_gain	1.0000
11:43320813:A:AG	acceptor_gain	1.0000
11:43320813:AT:A	acceptor_gain	1.0000
11:43320814:T:A	acceptor_gain	1.0000
11:43320814:T:G	acceptor_gain	1.0000
11:43320816:CCCAG:C	acceptor_loss	1.0000

AlphaMissense

3425 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:43312147:T:C	L7P	1.000
11:43312149:T:C	Y8H	1.000
11:43318652:T:G	Y28D	1.000
11:43318662:T:A	I31K	1.000
11:43318701:T:C	L44S	1.000
11:43318707:C:A	A46D	1.000
11:43318713:T:C	F48S	1.000
11:43318724:T:C	F52L	1.000
11:43318726:C:A	F52L	1.000
11:43318726:C:G	F52L	1.000
11:43318758:C:A	A63D	1.000
11:43318766:G:C	A66P	1.000
11:43318779:T:A	L70H	1.000
11:43318779:T:C	L70P	1.000
11:43318781:T:C	C71R	1.000
11:43318782:G:A	C71Y	1.000
11:43318783:T:G	C71W	1.000
11:43320825:G:C	R79P	1.000
11:43320833:G:C	A82P	1.000
11:43320846:T:C	L86P	1.000
11:43320891:T:A	I101K	1.000
11:43320894:T:C	L102P	1.000
11:43320903:T:C	L105P	1.000
11:43321443:G:C	A120P	1.000
11:43321447:T:C	L121P	1.000
11:43322012:T:A	I140K	1.000
11:43322036:G:C	R148T	1.000
11:43322036:G:T	R148I	1.000
11:43322037:A:C	R148S	1.000
11:43322037:A:T	R148S	1.000

dbSNP variants (sampled 300 via entrez): RS1000011936 (11:43328427 A>C), RS1000082828 (11:43335794 A>C), RS1000111116 (11:43316219 T>C), RS1000154251 (11:43328297 C>T), RS1000291477 (11:43335987 T>G), RS1000325505 (11:43341353 C>G), RS1000419191 (11:43344548 T>A), RS1000619374 (11:43317056 T>C), RS1000622864 (11:43335500 A>G), RS1000647570 (11:43335713 A>G), RS1000679587 (11:43317419 G>A,C), RS1000742330 (11:43311756 T>C), RS1000830654 (11:43311549 A>G), RS1001063927 (11:43330374 T>A), RS1001231800 (11:43344779 T>A,C)

Disease associations

OMIM: gene MIM:609774 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST000477_38	Cognitive performance	5.000000e-06
GCST003800_4	Response to bupropion in depression	7.000000e-07
GCST006291_25	Spherical equivalent or myopia (age of diagnosis)	5.000000e-08
GCST009391_1668	Metabolite levels	6.000000e-06
GCST010002_236	Refractive error	2.000000e-24
GCST011696_7	Alzheimer’s disease	9.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0003926	neuropsychological test
EFO:0004847	age at onset
EFO:0010470	carnosine measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067417 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.25	Kd	56.21	nM	CHEMBL5653589
7.25	ED50	56.21	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147874: Binding affinity to human API5 incubated for 45 mins by Kinobead based pull down assay	kd	0.0562	uM

CTD chemical–gene interactions

46 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	4
Resveratrol	affects cotreatment, increases expression, decreases expression	2
Doxorubicin	decreases response to substance, decreases expression	2
Ozone	affects cotreatment, increases oxidation, increases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
FR900359	decreases phosphorylation	1
testosterone enanthate	affects expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
testosterone undecanoate	affects cotreatment, decreases expression	1
arsenite	decreases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
coumarin	decreases phosphorylation	1
methacrylaldehyde	increases oxidation, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
CGP 52608	affects binding, increases reaction	1
CD 437	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	decreases expression	1
7-(benzylamino)-1,3,4,8-tetrahydropyrrolo(4,3,2-de)quinolin-8(1H)-one	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Sunitinib	increases expression	1
Zoledronic Acid	increases expression	1
Vorinostat	increases expression	1
Leflunomide	decreases expression	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, increases oxidation	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5650916	Binding	Binding affinity to human API5 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.