ANXA5

Summary

ANXA5 (annexin A5, HGNC:543) is a protein-coding gene on chromosome 4q27, encoding Annexin A5 (P08758). This protein is an anticoagulant protein that acts as an indirect inhibitor of the thromboplastin-specific complex, which is involved in the blood coagulation cascade.

The Annexin 5 gene spans 29 kb containing 13 exons, and encodes a single transcript of approximately 1.6 kb and a protein product with a molecular weight of about 35 kDa.The protein encoded by this gene belongs to the annexin family of calcium-dependent phospholipid binding proteins some of which have been implicated in membrane-related events along exocytotic and endocytotic pathways. Annexin 5 is a phospholipase A2 and protein kinase C inhibitory protein with calcium channel activity and a potential role in cellular signal transduction, inflammation, growth and differentiation. Annexin 5 has also been described as placental anticoagulant protein I, vascular anticoagulant-alpha, endonexin II, lipocortin V, placental protein 4 and anchorin CII. Polymorphisms in this gene have been implicated in various obstetric complications.

Source: NCBI Gene 308 — RefSeq curated summary.

At a glance

• Gene–disease (curated): pregnancy loss, recurrent, susceptibility to, 3 (Moderate, GenCC)
• GWAS associations: 6
• Clinical variants (ClinVar): 78 total
• Phenotypes (HPO): 3
• Druggable target: yes
• MANE Select transcript: NM_001154

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:543
Approved symbol	ANXA5
Name	annexin A5
Location	4q27
Locus type	gene with protein product
Status	Approved
Aliases	CPB-I, PAP-I, VAC-alph, RPRGL3
Ensembl gene	ENSG00000164111
Ensembl biotype	protein_coding
OMIM	131230
Entrez	308

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 27 protein_coding, 5 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000296511, ENST00000501272, ENST00000506395, ENST00000509016, ENST00000509648, ENST00000511552, ENST00000513428, ENST00000513523, ENST00000513728, ENST00000515017, ENST00000515717, ENST00000854795, ENST00000854796, ENST00000854797, ENST00000854798, ENST00000854799, ENST00000923799, ENST00000923800, ENST00000923801, ENST00000923802, ENST00000923803, ENST00000923804, ENST00000923805, ENST00000923806, ENST00000923807, ENST00000969927, ENST00000969928, ENST00000969929, ENST00000969930, ENST00000969931, ENST00000969932, ENST00000969933, ENST00000969934, ENST00000969935, ENST00000969936

RefSeq mRNA: 1 — MANE Select: NM_001154 NM_001154

CCDS: CCDS3720

Canonical transcript exons

ENST00000296511 — 13 exons

Exon	Start	End
ENSE00001377438	121696863	121696980
ENSE00001866494	121667946	121668527
ENSE00003466252	121684677	121684771
ENSE00003487997	121669954	121670012
ENSE00003492195	121686288	121686372
ENSE00003523368	121671547	121671642
ENSE00003528136	121677894	121677950
ENSE00003563676	121681671	121681761
ENSE00003607401	121678415	121678494
ENSE00003611119	121696581	121696624
ENSE00003624802	121683364	121683477
ENSE00003659224	121672533	121672626
ENSE00003691852	121669602	121669724

Expression profiles

Bgee: expression breadth ubiquitous, 305 present calls, max score 99.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 558.9560 / max 6803.0573, expressed in 1823 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
53837	551.6936	1823
53833	1.6558	105
53836	1.1742	585
53818	0.9958	577
53817	0.9388	541
53825	0.8541	457
53813	0.7581	421
53814	0.4859	261
53834	0.3686	67
53835	0.0311	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	99.65	gold quality
smooth muscle tissue	UBERON:0001135	99.50	gold quality
calcaneal tendon	UBERON:0003701	99.46	gold quality
endocervix	UBERON:0000458	99.45	gold quality
right lung	UBERON:0002167	99.45	gold quality
gall bladder	UBERON:0002110	99.44	gold quality
monocyte	CL:0000576	99.43	gold quality
ascending aorta	UBERON:0001496	99.43	gold quality
thoracic aorta	UBERON:0001515	99.43	gold quality
descending thoracic aorta	UBERON:0002345	99.43	gold quality
islet of Langerhans	UBERON:0000006	99.42	gold quality
synovial joint	UBERON:0002217	99.41	gold quality
upper lobe of lung	UBERON:0008948	99.41	gold quality
upper lobe of left lung	UBERON:0008952	99.41	gold quality
right coronary artery	UBERON:0001625	99.40	gold quality
peritoneum	UBERON:0002358	99.38	gold quality
cartilage tissue	UBERON:0002418	99.38	gold quality
adipose tissue of abdominal region	UBERON:0007808	99.38	gold quality
body of uterus	UBERON:0009853	99.38	gold quality
omental fat pad	UBERON:0010414	99.38	gold quality
right adrenal gland cortex	UBERON:0035827	99.36	gold quality
aorta	UBERON:0000947	99.35	gold quality
left adrenal gland	UBERON:0001234	99.35	gold quality
left coronary artery	UBERON:0001626	99.35	gold quality
mononuclear cell	CL:0000842	99.33	gold quality
left adrenal gland cortex	UBERON:0035825	99.32	gold quality
leukocyte	CL:0000738	99.31	gold quality
right adrenal gland	UBERON:0001233	99.31	gold quality
placenta	UBERON:0001987	99.31	gold quality
adrenal cortex	UBERON:0001235	99.30	gold quality

Single-cell (SCXA)

Detected in 34 experiment(s), a significant marker in 26.

Experiment	Marker?	Max mean expression
E-MTAB-7249	yes	5686.36
E-MTAB-8142	yes	2016.45
E-HCAD-29	yes	1312.31
E-GEOD-98556	yes	750.04
E-GEOD-93593	yes	398.92
E-GEOD-75140	yes	262.81
E-MTAB-6701	yes	117.16
E-HCAD-1	yes	99.75
E-HCAD-4	yes	81.75
E-CURD-122	yes	73.95
E-MTAB-8410	yes	52.14
E-GEOD-135922	yes	38.78
E-CURD-46	yes	30.24
E-MTAB-9221	yes	29.80
E-MTAB-9467	yes	27.87

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CDX1, CEBPB, NFKBIA, PBX1, SP1, TFAP2A, TLX2

miRNA regulators (miRDB)

41 targeting ANXA5, 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-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-802	99.61	67.70	1254
HSA-MIR-2054	99.20	68.89	1699
HSA-MIR-548L	99.06	70.90	2560
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-6877-3P	98.98	65.83	560
HSA-MIR-6819-3P	98.95	65.57	572
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-224-3P	98.91	68.42	1815
HSA-MIR-522-3P	98.91	68.56	1817
HSA-MIR-1301-3P	98.64	68.27	1071
HSA-MIR-5047	98.64	68.62	1035
HSA-MIR-6837-3P	98.42	66.71	1149
HSA-MIR-2681-3P	98.18	65.28	577

Literature-anchored findings (GeneRIF, showing 40)

• The NF-kappaB/Relish Activates miR-308 to Negatively Regulate Imd Pathway Immune Signaling in Drosophila. (PMID:37358278)
• Annexin V expression in apoptotic peripheral blood lymphocytes: an electron microscopic evaluation (PMID:11773704)
• In vivo imaging of acute cardiac rejection in human patients using (99m)technetium labeled compound. (PMID:12102261)
• A common polymorphism in the annexin V Kozak sequence (-1C>T) increases translation efficiency and plasma levels of annexin V, and decreases the risk of myocardial infarction in young patients. (PMID:12200370)
• The -1C>T mutation in this gene does not afffect plama levels of this protein (PMID:12732504)
• CR2-positive cells undergo apoptosis; the unmasking of Annexin V binding sites resembles the unmasking of CR2. Therefore, apoptotic cells from the same lineage may share a similar mechanism for neo-surface markers. (PMID:12798778)
• displacement of annexin A5 from cellular surfaces by antiphospholipid antibodies is not a common mechanism in patients with antiphospholipid antibodies (PMID:12871462)
• IGF-I activates specific apoptotic pathways (Caspase-3 activation, Annexin-V binding and DNA degradation in an osteosarcoma cell line. (PMID:14710359)
• a massive number of circulating annexin-V-binding neutrophils in the absence of apoptosis can be demonstrated in BTHS. These neutrophils expose an alternative substrate for annexin-V different from PS and not recognized by macrophages. (PMID:14764526)
• annexin V regulates coagulability in the blood stream by binding not only to phosphatidylserine but also to sulfatide (PMID:15173196)
• plasmas from patients with aPL antibodies with thromboembolism reduce both A5 binding to phospholipid and A5 anticoagulant activity, identifying a novel mechanism for thrombosis in the aPL syndrome. (PMID:15242878)
• B-helix calcium binding sites have an essential role in the membrane binding of annexin V (PMID:15280367)
• In mature sperm, caspase activation was only detected in annexin V fraction. Selection of annexin V-negative mature spermatozoa might be of relevance for fertility preservation, as this fraction shows no activated apoptosis during cryopreservation. (PMID:15286043)
• phosphatidylserine-annexin A5-mediated pinocytic pathway (PMID:15381697)
• Human colon adenocarcinoma cell differentiation is associated with an up-regulation of AnxA1, AnxA2, and AnxA5 and with a subcellular relocation of these proteins (PMID:15526283)
• analysis of Annexin A5-1C/T polymorphism in ischemic stroke (PMID:15634283)
• CRP and annexin A5 at physiological concentrations bind to distinct sites of negatively charged phospholipids present in oxidized LDL (PMID:15692104)
• The -1C to T polymorphism in the annexin A5 gene is not associated with the risk of acute myocardial infarction or sudden cardiac death in middle-aged Finnish males. (PMID:16025836)
• Reduction of annexin A5 and interference with its anticoagulant and binding activities are associated significantly with history of recurrent spontaneous pregnancy losses. Possible significant role for annexin A5 in maintenance of pregnancy. (PMID:16389029)
• AnxA5 is present in amniotic fluid and increases through gestation from 15 to 24 weeks. Elevated AF-AnxA5 levels were present in patients who developed intrauterine growth restriction. (PMID:16579937)
• Through an inducible association with the R2 subunit of the IFN-gamma receptor, annexin 5 modulates cellular responses to IFN-gamma by modulating signaling through the Jak-Stat1 pathway. (PMID:16670301)
• The -1T variant of the annexin V gene, which has been suggested to have a protective role against thrombotic disease, was evaluated in 140 women with pregnancy complications and 317 control women with uncomplicated pregnancies. (PMID:16704958)
• following cell activation, deltaPKC-annexin V binding is a transient and an essential step in the function of deltaPKC (PMID:16785226)
• Plasmas with beta2GPI-dependent LAC that recognize domain I displayed significantly increased AnxA5 resistance, suggesting that specifically anti-beta2GPI antibodies compete with AnxA5 for anionic phospholipids (PMID:17053060)
• Sequence analysis of 70 German recurrent pregnancy loss patients, carrying neither factor V Leiden nor a prothrombin mutation, revealed four consecutive nucleotide substitutions in the ANXA5 promoter, which were transmitted as a joint haplotype (M2). (PMID:17339269)
• Patients with recurrent miscarriage show elevated plasma levels of annexin V in presence of antiphospholipid antibodies (PMID:17363042)
• an Annexin A5 polymorphism may have a protective role against thrombotic episodes after the first myocardial infarct in young patients (PMID:17408414)
• Recombinant human annexin V homodimer, Diannexin, protects sinsuoidal endothelial cells from ischemia reperfusion damage. (PMID:17681182)
• myocardial AnxA5 upregulation is associated with hypertensive heart disease and impairment of systolic function in hypertensive patients, this association being independent of apoptosis. (PMID:17766279)
• annexin V is necessary for normal CFTR chloride channel activity. (PMID:17869070)
• ANXA5 deserves further attention and careful studies as the mechanism behind the majority of clinically significant cardiovascular ischemic disease (PMID:17893975)
• analysis of translocation and assembly at the plasma membrane and the nuclear envelope (PMID:18164291)
• adenosine triphosphate synthase alpha chain was up-regulated, whereas annexin II, annexin V, beta(2)-tubulin, and profilin 1 were down-regulated in nasopharyngeal cancer cell lines (PMID:18384219)
• Annexin V expression in human placenta is influenced by the carriership of the common haplotype M2. (PMID:18462735)
• GnRH stimulation of signaling pathway for annexin A5 mRNA expression is distinct from that of LHbeta mRNA and dependent more on MAPK. (PMID:18703851)
• Raised anxA5 expression induces an augmented function of DeltaF508-CFTR due to its increased membrane localization, suggesting that anxA5 is a potential therapeutic target in cystic fibrosis. (PMID:18773956)
• suggest that apoptosis in cultured monocytes, as evidenced by Annexin V(+), operates through genes well known in apoptosis, but that the process also involves additional genes not commonly associated with apoptosis (PMID:18951241)
• These findings indicate that the polymorphisms of ANXA6 are associated with osteonecrosis of the femoral head. (PMID:19345290)
• invasion capacity, a main characteristic of tumors, is at least partially regulated by annexin A5 in oral carcinoma (PMID:19372761)
• ANXA5 expression seems to be related to the tumor stage and clinical outcome of colorectal adenocarcinoma. Thus ANXA5 could serve as a prognostic marker for tumor progression. (PMID:19461527)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	anxa5b	ENSDARG00000016470
danio_rerio	anxa5a	ENSDARG00000026406
mus_musculus	Anxa5	ENSMUSG00000027712
rattus_norvegicus	Anxa5	ENSRNOG00000014453
drosophila_melanogaster	AnxB9	FBGN0000083
drosophila_melanogaster	AnxB11	FBGN0030749

Paralogs (12): ANXA13 (ENSG00000104537), ANXA10 (ENSG00000109511), ANXA11 (ENSG00000122359), ANXA1 (ENSG00000135046), ANXA7 (ENSG00000138279), ANXA3 (ENSG00000138772), ANXA9 (ENSG00000143412), ANXA2 (ENSG00000182718), ANXA4 (ENSG00000196975), ANXA6 (ENSG00000197043), ANXA8L1 (ENSG00000264230), ANXA8 (ENSG00000265190)

Protein

Protein identifiers

Annexin A5 — P08758 (reviewed: P08758)

Alternative names: Anchorin CII, Annexin V, Annexin-5, Calphobindin I, Endonexin II, Lipocortin V, Placental anticoagulant protein 4, Placental anticoagulant protein I, Thromboplastin inhibitor, Vascular anticoagulant-alpha

All UniProt accessions (6): D6RBE9, D6RBL5, D6RCN3, P08758, E9PHT9, V9HWE0

UniProt curated annotations — full annotation on UniProt →

Function. This protein is an anticoagulant protein that acts as an indirect inhibitor of the thromboplastin-specific complex, which is involved in the blood coagulation cascade.

Subunit / interactions. Monomer. Binds ATRX and EIF5B. Interacts with hepatitis B virus (HBV).

Post-translational modifications. S-nitrosylation is induced by interferon-gamma and oxidatively-modified low-densitity lipoprotein (LDL(ox)) possibly implicating the iNOS-S100A8/9 transnitrosylase complex.

Disease relevance. Pregnancy loss, recurrent, 3 (RPRGL3) [MIM:614391] A common complication of pregnancy, resulting in spontaneous abortion before the fetus has reached viability. The term includes all miscarriages from the time of conception until 24 weeks of gestation. Recurrent pregnancy loss is defined as 3 or more consecutive spontaneous abortions. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Domain organisation. The [IL]-x-C-x-x-[DE] motif is a proposed target motif for cysteine S-nitrosylation mediated by the iNOS-S100A8/A9 transnitrosylase complex. A pair of annexin repeats may form one binding site for calcium and phospholipid.

Similarity. Belongs to the annexin family.

RefSeq proteins (1): NP_001145* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001464	Annexin	Family
IPR002392	ANX5	Family
IPR018252	Annexin_repeat_CS	Conserved_site
IPR018502	Annexin_repeat	Repeat
IPR037104	Annexin_sf	Homologous_superfamily

Pfam: PF00191

UniProt features (45 total): helix 21, modified residue 8, repeat 4, strand 3, cross-link 2, sequence conflict 2, turn 2, initiator methionine 1, chain 1, short sequence motif 1

Structure

Experimental structures (PDB)

17 structures.

PDB	Method	Resolution (Å)
8H9Z	X-RAY DIFFRACTION	1.42
8GYC	X-RAY DIFFRACTION	1.8
1ANX	X-RAY DIFFRACTION	1.9
1HVD	X-RAY DIFFRACTION	2
1HVF	X-RAY DIFFRACTION	2
8H0J	X-RAY DIFFRACTION	2.23
1AVH	X-RAY DIFFRACTION	2.3
1AVR	X-RAY DIFFRACTION	2.3
1HVE	X-RAY DIFFRACTION	2.3
2XO3	X-RAY DIFFRACTION	2.3
1ANW	X-RAY DIFFRACTION	2.4
6K25	X-RAY DIFFRACTION	2.4
1SAV	X-RAY DIFFRACTION	2.5
6K22	X-RAY DIFFRACTION	2.75
2XO2	X-RAY DIFFRACTION	2.8
1HAK	X-RAY DIFFRACTION	3
1HVG	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P08758-F1	96.33	0.94

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 (10): 76, 79, 97, 101, 290, 29, 29, 2, 37, 70

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation
R-HSA-109582	Hemostasis
R-HSA-76002	Platelet activation, signaling and aggregation
R-HSA-76005	Response to elevated platelet cytosolic Ca2+

MSigDB gene sets: 329 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, GOBP_REGULATION_OF_COAGULATION, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, DITTMER_PTHLH_TARGETS_UP, GOCC_CELL_SURFACE, LINDGREN_BLADDER_CANCER_CLUSTER_2A_DN, GOBP_NEGATIVE_REGULATION_OF_COAGULATION, GOBP_WOUND_HEALING, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, ROSS_LEUKEMIA_WITH_MLL_FUSIONS, CASORELLI_APL_SECONDARY_VS_DE_NOVO_UP, WINTER_HYPOXIA_METAGENE, BROWN_MYELOID_CELL_DEVELOPMENT_UP, GOBP_HEMOSTASIS, GUENTHER_GROWTH_SPHERICAL_VS_ADHERENT_DN

GO Biological Process (5): signal transduction (GO:0007165), blood coagulation (GO:0007596), negative regulation of apoptotic process (GO:0043066), negative regulation of coagulation (GO:0050819), hemostasis (GO:0007599)

GO Molecular Function (6): phosphatidylserine binding (GO:0001786), phospholipase inhibitor activity (GO:0004859), calcium ion binding (GO:0005509), phospholipid binding (GO:0005543), calcium-dependent phospholipid binding (GO:0005544), protein binding (GO:0005515)

GO Cellular Component (13): extracellular region (GO:0005576), cytoplasm (GO:0005737), cytosol (GO:0005829), focal adhesion (GO:0005925), external side of plasma membrane (GO:0009897), vesicle membrane (GO:0012506), membrane (GO:0016020), extracellular matrix (GO:0031012), sarcolemma (GO:0042383), extracellular exosome (GO:0070062), endothelial microparticle (GO:0072563), cytoplasmic vesicle (GO:0031410), zymogen granule membrane (GO:0042589)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Response to elevated platelet cytosolic Ca2+	1
Hemostasis	1
Platelet activation, signaling and aggregation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
coagulation	2
phospholipid binding	2
cytoplasm	2
plasma membrane	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
hemostasis	1
wound healing	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
regulation of coagulation	1
negative regulation of multicellular organismal process	1
regulation of body fluid levels	1
anion binding	1
modified amino acid binding	1
glycerophospholipase activity	1
lipase inhibitor activity	1
metal ion binding	1
lipid binding	1
binding	1
intracellular anatomical structure	1
cell-substrate junction	1
cell surface	1
side of membrane	1
organelle membrane	1
vesicle	1
external encapsulating structure	1
extracellular vesicle	1
blood microparticle	1
intracellular vesicle	1
secretory granule membrane	1
zymogen granule	1

Protein interactions and networks

STRING

5688 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANXA5	GAPDH	P00354	942
ANXA5	ACTB	P02570	940
ANXA5	CASP3	P42574	919
ANXA5	BCL2	P10415	898
ANXA5	CCK	P06307	891
ANXA5	PXDNL	A1KZ92	887
ANXA5	PXDN	Q92626	886
ANXA5	CASP9	P55211	885
ANXA5	PARP1	P09874	874
ANXA5	F3	P13726	852
ANXA5	HEPN1	Q6WQI6	844
ANXA5	CYCS	P00001	841
ANXA5	CASP8	Q14790	837
ANXA5	ACTG1	P02571	827
ANXA5	AKT1	P31749	819

IntAct

130 interactions, top by confidence:

A	B	Type	Score
PIK3CA	PIK3R2	psi-mi:“MI:0914”(association)	0.900
PPP2R1B	STRN	psi-mi:“MI:0914”(association)	0.730
RPRD1B	POLR2D	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
GSC2	ANXA5	psi-mi:“MI:0915”(physical association)	0.560
ANXA5	HSPB1	psi-mi:“MI:0915”(physical association)	0.560
ANXA5	WFS1	psi-mi:“MI:0915”(physical association)	0.560
ANXA5	OPTN	psi-mi:“MI:0915”(physical association)	0.560
TINF2	ANXA5	psi-mi:“MI:0915”(physical association)	0.510
LMTK3	GPI	psi-mi:“MI:0914”(association)	0.420
ANXA5	LRRC15	psi-mi:“MI:0915”(physical association)	0.400
Pds5a		psi-mi:“MI:0915”(physical association)	0.400
Bles03		psi-mi:“MI:0915”(physical association)	0.400
	GNAT3	psi-mi:“MI:0915”(physical association)	0.400
TBX3	ANXA5	psi-mi:“MI:0915”(physical association)	0.400
ANXA5	OR1M1	psi-mi:“MI:0915”(physical association)	0.400
Atrx	ANXA5	psi-mi:“MI:0915”(physical association)	0.400
Dnmt1	ANXA5	psi-mi:“MI:0915”(physical association)	0.400
Eif5b	ANXA5	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (266): ANXA5 (Affinity Capture-MS), ANXA5 (Affinity Capture-MS), ANXA5 (Affinity Capture-MS), LRRC15 (Affinity Capture-MS), ANXA5 (Co-fractionation), ANXA5 (Co-fractionation), ANXA5 (Co-fractionation), ANXA5 (Co-fractionation), GCN1L1 (Co-fractionation), PDCD6 (Co-fractionation), PDIA3 (Co-fractionation), TUBB (Co-fractionation), ANXA5 (Affinity Capture-MS), ANXA5 (Synthetic Lethality), ANXA5 (Affinity Capture-MS)

ESM2 similar proteins: A2SW69, A5A6L7, A6NMY6, O35639, O35640, O97529, P04272, P07355, P07356, P08132, P08758, P09525, P12429, P13214, P13928, P14668, P14669, P14824, P14950, P17153, P17785, P19620, P22464, P24551, P24801, P26256, P27006, P27216, P48036, P50994, P51074, P55260, P70075, P81287, P93157, P97429, Q07936, Q29471, Q2Q1M6, Q3SWX7

Diamond homologs: A2SW69, A5A6L7, A5A6M2, A6NMY6, C0HJG9, C1L7Y4, C4QH88, O35639, O35640, O76027, O97529, P04083, P04272, P07150, P07355, P07356, P08132, P08133, P08758, P09525, P10107, P12429, P13214, P13928, P14087, P14668, P14669, P14824, P14950, P17153, P17785, P19619, P19620, P20072, P20073, P22464, P22465, P24551, P24639, P24801

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 138 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Packaging Of Telomere Ends	5	11.1×	4e-03
Extra-nuclear estrogen signaling	6	10.3×	2e-03
Recognition and association of DNA glycosylase with site containing an affected purine	5	10.3×	5e-03
Cleavage of the damaged purine	5	10.3×	5e-03
Inhibition of DNA recombination at telomere	6	10.2×	2e-03
Recognition and association of DNA glycosylase with site containing an affected pyrimidine	5	9.3×	5e-03
Cleavage of the damaged pyrimidine	5	9.3×	5e-03
Cellular Senescence	6	8.3×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of telomere maintenance	7	31.4×	2e-06
positive regulation of miRNA transcription	5	12.7×	8e-03
energy homeostasis	5	11.9×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	46
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2027 predictions. Top by Δscore:

Variant	Effect	Δscore
4:121669637:T:TA	donor_gain	1.0000
4:121669949:CTTA:C	donor_loss	1.0000
4:121669950:TTA:T	donor_loss	1.0000
4:121669951:TA:T	donor_loss	1.0000
4:121669952:A:AC	donor_gain	1.0000
4:121669953:C:CC	donor_gain	1.0000
4:121669953:C:T	donor_loss	1.0000
4:121669953:CCTT:C	donor_gain	1.0000
4:121670008:TTTCA:T	acceptor_gain	1.0000
4:121670009:TTCA:T	acceptor_gain	1.0000
4:121670010:TCA:T	acceptor_gain	1.0000
4:121670010:TCAC:T	acceptor_loss	1.0000
4:121670011:CA:C	acceptor_gain	1.0000
4:121670011:CAC:C	acceptor_gain	1.0000
4:121670012:AC:A	acceptor_loss	1.0000
4:121670013:C:CC	acceptor_gain	1.0000
4:121670013:CTAA:C	acceptor_loss	1.0000
4:121671641:CA:C	acceptor_gain	1.0000
4:121671643:C:CC	acceptor_gain	1.0000
4:121672531:AC:A	donor_gain	1.0000
4:121672532:CC:C	donor_gain	1.0000
4:121672622:AAAGC:A	acceptor_gain	1.0000
4:121672623:AAGC:A	acceptor_gain	1.0000
4:121672624:AGC:A	acceptor_gain	1.0000
4:121672625:GC:G	acceptor_gain	1.0000
4:121672626:CC:C	acceptor_gain	1.0000
4:121672627:CTGCA:C	acceptor_loss	1.0000
4:121677889:CTCA:C	donor_loss	1.0000
4:121677890:TCACC:T	donor_loss	1.0000
4:121677891:CACCT:C	donor_loss	1.0000

AlphaMissense

2080 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:121684695:A:C	F57L	0.996
4:121684695:A:T	F57L	0.996
4:121684697:A:G	F57L	0.996
4:121684718:G:T	R50S	0.996
4:121669641:A:C	F288L	0.995
4:121669641:A:T	F288L	0.995
4:121669643:A:G	F288L	0.995
4:121672622:A:G	L179S	0.995
4:121683380:A:G	L96P	0.994
4:121671594:A:T	I225N	0.993
4:121684717:C:G	R50P	0.993
4:121672614:C:G	A182P	0.992
4:121683461:A:G	L69P	0.992
4:121669678:C:A	R276M	0.991
4:121669980:C:G	A252P	0.990
4:121672577:A:G	F194S	0.989
4:121677899:C:G	A176P	0.989
4:121683449:A:G	L73P	0.989
4:121684732:C:G	R45P	0.989
4:121686311:A:T	L24H	0.989
4:121671558:A:G	L237P	0.988
4:121677898:G:T	A176D	0.988
4:121678419:A:G	L157P	0.988
4:121686303:C:G	A27P	0.988
4:121669962:C:G	A258P	0.987
4:121669970:A:G	L255P	0.987
4:121671588:C:G	R227P	0.987
4:121669642:A:G	F288S	0.986
4:121672541:A:G	L206S	0.986
4:121672576:A:C	F194L	0.986

dbSNP variants (sampled 300 via entrez): RS1000010176 (4:121668238 A>C), RS1000422058 (4:121694677 C>A), RS1000502929 (4:121697883 C>T), RS1000510467 (4:121680425 A>G), RS10006900 (4:121694152 T>A,G), RS10006927 (4:121694213 T>A,C), RS1000754991 (4:121695933 A>C), RS10008313 (4:121678868 T>C), RS1000856390 (4:121685795 C>T), RS10008778 (4:121693252 C>A,T), RS1000956956 (4:121689979 A>G), RS1001021176 (4:121671809 T>C), RS1001040789 (4:121683177 G>A,T), RS1001156409 (4:121683591 T>C), RS10011722 (4:121686818 A>C,G,T)

Disease associations

OMIM: gene MIM:131230 | disease phenotypes: MIM:614391

GenCC curated gene-disease

Disease	Classification	Inheritance
pregnancy loss, recurrent, susceptibility to, 3	Moderate	Autosomal dominant

Mondo (1): pregnancy loss, recurrent, susceptibility to, 3 (MONDO:0013729)

Orphanet (0):

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0011462	Young adult onset
HP:0200067	Recurrent spontaneous abortion

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001113_13	Age at smoking initiation in chronic obstructive pulmonary disease	5.000000e-07
GCST006138_30	Resting-state electroencephalogram vigilance	2.000000e-06
GCST009439_15	Age-related cognitive decline (language) (slope of z-scores)	5.000000e-07
GCST90020024_682	A body shape index	1.000000e-09
GCST90020025_613	Waist-to-hip ratio adjusted for BMI	6.000000e-09
GCST90020027_1940	Waist-hip index	5.000000e-09

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0005670	smoking initiation
EFO:0004357	electroencephalogram measurement
EFO:0007710	cognitive decline measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066971 (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
7.28	Kd	53.02	nM	CHEMBL5653589
7.28	ED50	53.02	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	2147858: Binding affinity to human ANXA5 incubated for 45 mins by Kinobead based pull down assay	kd	0.0530	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, decreases methylation, affects cotreatment	8
Tretinoin	decreases expression, increases reaction, increases expression	5
Cisplatin	decreases expression, increases reaction, increases expression	3
Smoke	decreases expression, increases abundance	3
bisphenol A	decreases expression, increases expression	2
sodium arsenite	increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
bisphenol S	affects expression, increases expression	2
Decitabine	increases expression, affects cotreatment, affects expression	2
Air Pollutants	increases abundance, decreases expression	2
Benzo(a)pyrene	increases expression	2
Calcium	affects binding, increases activity, increases reaction	2
Paraquat	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Phosphatidylserines	affects binding, increases reaction, affects localization	2
Cyclosporine	increases expression	2
Cadmium Chloride	increases expression	2
Nanotubes, Carbon	increases expression, affects expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
TAK-243	decreases sumoylation	1
triphenyl phosphate	affects expression	1
glycidyl methacrylate	increases expression	1
lead acetate	affects binding, increases activity	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
salinomycin	decreases expression	1
pyrithione zinc	increases expression	1
tributyltin	decreases expression, increases reaction	1
triphenyltin chloride	decreases expression, increases reaction	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5650900	Binding	Binding affinity to human ANXA5 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

6 cell lines: 6 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1VA	Abcam A-549 ANXA5 KO	Cancer cell line	Male
CVCL_D1ZX	Abcam HCT 116 ANXA5 KO	Cancer cell line	Male
CVCL_D2N5	Abcam THP-1 ANXA5 KO	Cancer cell line	Male
CVCL_E6IT	FTO 9.1	Cancer cell line	Male
CVCL_SC68	HAP1 ANXA5 (-) 1	Cancer cell line	Male
CVCL_XL37	HAP1 ANXA5 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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