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): 41 total
• GTEx eGene: eQTL in 12 tissues, sQTL in 0 (q < 0.05)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.21 (highly constrained)
• 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: 34 — 28 protein_coding, 3 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000531273

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 5, TSL 3: 2, TSL 5: 3

ENST00000531273, ENST00000378852, ENST00000420461, ENST00000455725, ENST00000526394, ENST00000529334, ENST00000529932, ENST00000530300, ENST00000532267, ENST00000534600, ENST00000534695, ENST00000866289, ENST00000866290, ENST00000866291, ENST00000866292, ENST00000866293, ENST00000866294, ENST00000866295, ENST00000931881, ENST00000949751, ENST00001003232, ENST00001003233, ENST00001043104, ENST00001043105, ENST00001043108, ENST00001081311, ENST00001081312, ENST00001081313, ENST00001100572, ENST00001100573, ENST00001117000, ENST00001122658, ENST00001122659, ENST00001144291

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.

Highest expression (Bgee): islet of Langerhans, rectum, ventricular zone, superficial temporal artery, oocyte.

Genetic regulation across tissues (GTEx eQTL / sQTL)

API5 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 12 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

12 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Esophagus Mucosa	eqtl	1.3e-18	-0.16	11:43311926:G:T
Whole Blood	eqtl	1.0e-09	-0.10	11:43311926:G:T
Skin Not Sun Exposed Suprapubic	eqtl	6.4e-04	-0.09	11:43525148:A:G
Cells Cultured fibroblasts	eqtl	2.8e-03	-0.11	11:43316326:T:A
Skin Sun Exposed Lower leg	eqtl	3.9e-03	-0.07	11:43406449:T:C
Adipose Visceral Omentum	eqtl	7.9e-03	-0.21	11:43513338:A:G
Artery Tibial	eqtl	2.4e-02	+0.18	11:43989426:A:G
Thyroid	eqtl	3.0e-02	-0.42	11:44310000:G:A
Brain Cerebellar Hemisphere	eqtl	3.3e-02	+0.19	11:44155504:A:T
Breast Mammary Tissue	eqtl	3.5e-02	+0.17	11:43250017:G:A
Brain Putamen basal ganglia	eqtl	3.9e-02	-0.87	11:42433377:G:C
Artery Aorta	eqtl	4.9e-02	-0.08	11:42383912:G:T

FANTOM5 promoters

2 alternative TSS:

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

Top tissues by expression

showing 100 of 295 tissues 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
tonsil	UBERON:0002372	94.47	gold quality
pancreas	UBERON:0001264	94.39	gold quality
lower lobe of lung	UBERON:0008949	94.32	gold quality
gall bladder	UBERON:0002110	94.26	gold quality
body of pancreas	UBERON:0001150	94.25	gold quality
jejunum	UBERON:0002115	94.19	gold quality
lateral globus pallidus	UBERON:0002476	94.16	gold quality
superior surface of tongue	UBERON:0007371	94.16	gold quality
lateral nuclear group of thalamus	UBERON:0002736	94.15	gold quality
saphenous vein	UBERON:0007318	94.13	gold quality
endothelial cell	CL:0000115	94.11	gold quality
urethra	UBERON:0000057	94.10	gold quality
tendon	UBERON:0000043	94.06	gold quality
substantia nigra pars reticulata	UBERON:0001966	93.98	gold quality
uterus	UBERON:0000995	93.97	gold quality
subthalamic nucleus	UBERON:0001906	93.97	gold quality
substantia nigra pars compacta	UBERON:0001965	93.97	gold quality
inferior vagus X ganglion	UBERON:0005363	93.93	gold quality
nipple	UBERON:0002030	93.76	gold quality
pharyngeal mucosa	UBERON:0000355	93.73	gold quality
blood vessel layer	UBERON:0004797	93.73	gold quality
pigmented layer of retina	UBERON:0001782	93.72	gold quality
corpus callosum	UBERON:0002336	93.66	gold quality
popliteal artery	UBERON:0002250	93.62	gold quality
tibial artery	UBERON:0007610	93.62	gold quality
synovial joint	UBERON:0002217	93.54	gold quality
trigeminal ganglion	UBERON:0001675	93.53	gold quality
cerebellar cortex	UBERON:0002129	93.50	gold quality
nasal cavity mucosa	UBERON:0001826	93.49	gold quality
cerebellar hemisphere	UBERON:0002245	93.49	gold quality
caput epididymis	UBERON:0004358	93.45	gold quality
colonic mucosa	UBERON:0000317	93.40	gold quality
corpus epididymis	UBERON:0004359	93.40	gold quality
prefrontal cortex	UBERON:0000451	93.33	gold quality
cardia of stomach	UBERON:0001162	93.33	gold quality
mammalian vulva	UBERON:0000997	93.30	gold quality
urinary bladder	UBERON:0001255	93.30	gold quality
cerebellum	UBERON:0002037	93.29	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.27	gold quality
myometrium	UBERON:0001296	93.26	gold quality
mammary duct	UBERON:0001765	93.25	gold quality
saliva-secreting gland	UBERON:0001044	93.22	gold quality
female reproductive system	UBERON:0000474	93.21	gold quality
body of uterus	UBERON:0009853	93.17	gold quality
upper leg skin	UBERON:0004262	93.07	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.06	gold quality
dorsal root ganglion	UBERON:0000044	93.01	gold quality
seminal vesicle	UBERON:0000998	93.01	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.01	gold quality
medulla oblongata	UBERON:0001896	92.98	gold quality
sigmoid colon	UBERON:0001159	92.96	gold quality
lower esophagus	UBERON:0013473	92.96	gold quality
lower esophagus muscularis layer	UBERON:0035833	92.96	gold quality
aorta	UBERON:0000947	92.93	gold quality
esophagus	UBERON:0001043	92.93	gold quality
right coronary artery	UBERON:0001625	92.93	gold quality
minor salivary gland	UBERON:0001830	92.91	gold quality
muscle layer of sigmoid colon	UBERON:0035805	92.91	gold quality
stromal cell of endometrium	CL:0002255	92.90	gold quality
large intestine	UBERON:0000059	92.89	gold quality
descending thoracic aorta	UBERON:0002345	92.87	gold quality
superior vestibular nucleus	UBERON:0007227	92.86	gold quality
intestine	UBERON:0000160	92.85	gold quality
vagina	UBERON:0000996	92.84	gold quality
left uterine tube	UBERON:0001303	92.84	gold quality
mouth mucosa	UBERON:0003729	92.78	gold quality
colon	UBERON:0001155	92.77	gold quality
spinal cord	UBERON:0002240	92.77	gold quality
pons	UBERON:0000988	92.76	gold quality
left coronary artery	UBERON:0001626	92.76	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Thymus	tissue	57.9
Corpus callosum	tissue	54.9
Postcentral gyrus	tissue	54.7
Caudate putamen	tissue	54.1
Liver	tissue	53.9	low
Tonsil	tissue	53.6	high
Putamen	tissue	53.3
Nucleus accumbens	tissue	52.6
Midbrain	tissue	52.2
Frontal cortex	tissue	52.1
Hippocampal formation	tissue	52.0
Spinal cord	tissue	51.4
Lymph node	tissue	50.0	low
Thyroid gland	tissue	48.1	low
Thalamus	tissue	47.5
Septum	tissue	47.3
Pons	tissue	46.7
Superior colliculi	tissue	46.6
Medulla oblongata	tissue	46.4
Cerebral cortex	tissue	46.3	medium
Occipital cortex	tissue	46.3
Locus coeruleus	tissue	46.2
Kidney	tissue	45.9	medium
Substantia nigra	tissue	45.6
Somatosensory cortex	tissue	45.6
Hippocampus	tissue	44.8	low
Ventral forebrain	tissue	44.8
Hypothalamus	tissue	44.7
Basal ganglia	tissue	44.0	low
Motor cortex	tissue	43.9
Rectum	tissue	43.8	medium
Parathyroid gland	tissue	43.8
Choroid plexus	tissue	43.8
Smooth muscle	tissue	43.5	not detected
Pancreas	tissue	43.3	medium
Cerebellum	tissue	43.3	low
Small intestine	tissue	42.9	high
Breast	tissue	42.8	low
Prefrontal cortex	tissue	42.2
Olfactory bulb	tissue	42.1
Esophagus	tissue	42.0	medium
Entorhinal cortex	tissue	42.0
Periaqueductal gray	tissue	41.8
Colon	tissue	41.5	medium
Urinary bladder	tissue	41.3	high
Retina	tissue	40.9
Appendix	tissue	40.9	high
Retrosplenial and cingulate cortex	tissue	40.6
Duodenum	tissue	40.3	medium
Temporal cortex	tissue	39.8
Retrosplenial cortex	tissue	39.6
Endometrium 1	tissue	39.4	medium
Stomach 1	tissue	38.8	low
Spleen	tissue	38.0	not detected
Skin 1	tissue	37.9	medium
Prostate	tissue	37.9	high
Amygdala	tissue	37.4
Seminal vesicle	tissue	37.2	low
Cervix	tissue	37.0	high
Salivary gland	tissue	36.8	not detected

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Cerebellar cortex (69.4), Corpus callosum, splenium (white matter) (68.0), Corpus callosum, genu (white matter) (67.4), Occipital cortex (white matter) (65.2), Lateral funiculus (white matter) (64.2).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting API5 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 174 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.211, missense Z 3.68 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000531273 splits into 3 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
11:43,312,128–43,323,501	127 / 237.6	0.53	no
11:43,323,502–43,323,580	37 / 31.3	1.18	no
11:43,323,581–43,342,507	168 / 343.9	0.49	no

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

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5R644	99.8%	Diamond
Xenopus laevis	Q6DDM4	96.6%	Diamond
Gallus gallus	Q5ZMW3	95.0%	Diamond
Dictyostelium discoideum	Q54CL0	37.0%	Diamond
Oryza sativa Japonica Group	Q6Z6S1	32.6%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
TTC17	protein-coding	55761
MIR670	ncRNA	100313777
HSD17B12	protein-coding	51144

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 (66 total): helix 34, 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 by resolution:

PDB	Title	Method	Resolution (Å)
3U0R	Helical repeat structure of apoptosis inhibitor 5 reveals protein-protein interaction …	X-RAY DIFFRACTION	2.5
3V6A	Helical repeat structure of apoptosis inhibitor 5 reveals protein-protein interaction …	X-RAY DIFFRACTION	2.6
6L4O	Crystal structure of API5-FGF2 complex	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nuclear speckles

Antibody reliability (HPA): IH approved · IF enhanced

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)

Type	Positions
Phosphoserine	462, 464, 469
Omega-n-methylarginine	500
N6-acetyllysine	251
Phosphothreonine	399

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

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 (2): apoptotic process (GO:0006915), negative regulation of apoptotic process (GO:0043066)

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

15 GO namespaces:

Category	Terms
cellular anatomical structure	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 6 of 10 annotations. The rest are phylogenetic / computational / electronic (IEA).

6 experimentally-supported GO terms:

GO term	NS	Evidence
negative regulation of apoptotic process	BP	mutant phenotype
membrane	CC	high-throughput assay
nuclear speck	CC	direct assay
nucleus	CC	direct assay
RNA binding	MF	high-throughput assay
fibroblast growth factor binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 1,668 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
API5	TTC17	Q96AE7	530
API5	XIAP	P98170	445
API5	AP1S1	P61966	427
API5	ACIN1	Q9UKV3	403
API5	PIM3	Q86V86	398
API5	PIM2	Q9P1W9	397
API5	SAMM50	Q9Y512	374
API5	FNDC3B	Q53EP0	370
API5	GPHB5	Q86YW7	370
API5	CRLF3	Q8IUI8	369
API5	CASP2	P42575	366
API5	FGF2	P09038	365
API5	A0A2R8YFG2	A0A2R8YFG2	364
API5	FAF1	Q9UNN5	362
API5	CAAP1	Q9H8G2	353

IntAct

Human interaction partners of API5 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

10 partners by confidence:

Partner	Interaction type	MIscore	Records
DDX39B	physical association	0.560	1
ACIN1	physical association	0.460	5
CEP112	physical association	0.400	1
FRG2	physical association	0.400	1
H1-9P	physical association	0.400	1
LTV1	physical association	0.400	1
OSGEPL1	physical association	0.400	1
SOCS6	physical association	0.400	1
HTT	physical association	0.370	1
PRKAB1	physical association	0.000	1

BioGRID (224 interactions; top human partners by supporting records): DDX39A (Co-fractionation; 3 records), ACIN1 (Affinity Capture-MS; 2 records), CDC5L (Affinity Capture-MS; 2 records), CTNNB1 (Affinity Capture-MS; 2 records), DDX27 (Affinity Capture-MS; 2 records), DDX39B (Affinity Capture-MS; 2 records), EBNA1BP2 (Affinity Capture-MS; 2 records), HNRNPK (Affinity Capture-MS; 2 records), HNRNPL (Affinity Capture-MS; 2 records), HNRNPU (Affinity Capture-MS; 2 records), ILF3 (Affinity Capture-MS; 2 records), MCM9 (Affinity Capture-MS; 2 records), PARK2 (Affinity Capture-MS; 2 records), PARP12 (Affinity Capture-MS; 2 records), SNW1 (Affinity Capture-MS; 2 records)

Protein complexes (CORUM) (2)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

2 complexes by size:

Complex	Subunits	Members
★ Emerin complex 52	23	DDX39A, ILF3, LEMD3, RBL2, H1-1, HNRNPK, HNRNPU, IQGAP1, NMI, PDCD4, SNRPD1, THRA, API5, CKB, EMD, HDGF, LSM8, YWHAQ, ACTB, C1QBP, HNRNPL, LMNB1, YWHAE
FIF-FGR2 complex	2	API5, FGF2

Disease & clinical

Genetic variants

Variant evidence for API5: 41 ClinVar records (0 pathogenic / likely pathogenic); 6 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	2
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 24 predictions of 1,121):

Position(s)	Effect	Δscore	Sites
11:43312197	donor_loss	1.0000	2
11:43318634	acceptor_gain	1.0000
11:43318638–43318639	acceptor_loss	1.0000	5
11:43318802–43318803	donor_loss	1.0000	3
11:43320806	acceptor_gain	1.0000
11:43320810–43320811	acceptor_gain	1.0000	2
11:43320814	acceptor_gain	1.0000	2
11:43320819	acceptor_loss	1.0000
11:43320915	donor_loss	1.0000	2
11:43321409–43321410	acceptor_loss	1.0000	5

AlphaMissense

2,143 missense substitutions predicted likely pathogenic (of 3,425 scored), across 452 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M318	9	0.932	0.999
M195	9	0.885	0.997
N420	8	0.998	1.000
D427	8	0.998	1.000
F340	8	0.997	1.000
F429	8	0.997	1.000
D69	8	0.996	0.998
F48	8	0.995	1.000
D73	8	0.993	0.999
D100	8	0.993	0.998
F191	8	0.993	1.000
D185	8	0.992	0.999
H351	8	0.992	1.000
S341	8	0.991	1.000
F380	8	0.990	0.998
H430	8	0.989	1.000
F249	8	0.987	0.999
F373	8	0.984	0.999
D236	8	0.979	0.994
S489	8	0.975	0.998

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	5.79e-07
Kidney Chromophobe (TCGA)	unfavorable	6.12e-06
Rectum Adenocarcinoma (TCGA)	favorable	0.00046

Disease associations

OMIM: gene MIM:609774 | disease phenotypes:

GWAS associations

6 associations:

Study	Trait	p-value
GCST010002_188	Refractive error	2e-24
GCST006291_140	Spherical equivalent or myopia (age of diagnosis)	5e-8
GCST011696_7	Alzheimer’s disease	9e-8
GCST003800_4	Response to bupropion in depression	7e-7
GCST000477_11	Cognitive performance	5e-6
GCST009391_1768	Metabolite levels	6e-6

EFO canonical traits (from GWAS)

3 canonical traits:

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 (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

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	increases expression, affects cotreatment	4
Resveratrol	affects cotreatment, increases expression, decreases expression	2
Doxorubicin	decreases response to substance, decreases expression	2
Ozone	increases expression, affects cotreatment, increases oxidation	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	affects cotreatment, increases oxidation	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
CGP 52608	increases reaction, affects binding	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*

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_F4YY	EDITGENE API5 Knockout HEK293 Cell Line	Transformed cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for API5 across ~30M SureChEMBL compounds — explore on Sugi Predict.