ANXA4

Summary

ANXA4 (annexin A4, HGNC:542) is a protein-coding gene on chromosome 2p13.3, encoding Annexin A4 (P09525). Calcium/phospholipid-binding protein which promotes membrane fusion and is involved in exocytosis.

Annexin IV (ANX4) belongs to the annexin family of calcium-dependent phospholipid binding proteins. Although their functions are still not clearly defined, several members of the annexin family have been implicated in membrane-related events along exocytotic and endocytotic pathways. ANX4 has 45 to 59% identity with other members of its family and shares a similar size and exon-intron organization. Isolated from human placenta, ANX4 encodes a protein that has possible interactions with ATP, and has in vitro anticoagulant activity and also inhibits phospholipase A2 activity. ANX4 is almost exclusively expressed in epithelial cells. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 307 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 70 total
• Druggable target: yes
• MANE Select transcript: NM_001153

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:542
Approved symbol	ANXA4
Name	annexin A4
Location	2p13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000196975
Ensembl biotype	protein_coding
OMIM	106491
Entrez	307

Gene structure

Transcript identifiers

Ensembl transcripts: 57 — 47 protein_coding, 4 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay, 3 retained_intron

ENST00000394295, ENST00000409920, ENST00000418066, ENST00000460439, ENST00000460942, ENST00000468815, ENST00000471395, ENST00000472124, ENST00000477632, ENST00000484219, ENST00000487351, ENST00000635311, ENST00000892545, ENST00000892547, ENST00000892549, ENST00000892551, ENST00000892553, ENST00000892555, ENST00000892557, ENST00000892559, ENST00000892561, ENST00000892562, ENST00000892563, ENST00000892564, ENST00000892565, ENST00000892566, ENST00000892567, ENST00000892568, ENST00000892569, ENST00000892570, ENST00000892571, ENST00000892572, ENST00000892573, ENST00000892574, ENST00000892575, ENST00000892576, ENST00000892577, ENST00000892578, ENST00000892579, ENST00000892580, ENST00000892581, ENST00000892582, ENST00000892583, ENST00000892584, ENST00000892585, ENST00000892586, ENST00000892587, ENST00000892588, ENST00000892589, ENST00000892590, ENST00000892591, ENST00000939478, ENST00000939479, ENST00000955418, ENST00000955419, ENST00000955420, ENST00000955421

RefSeq mRNA: 5 — MANE Select: NM_001153 NM_001153, NM_001320698, NM_001320700, NM_001320702, NM_001365496

CCDS: CCDS1894, CCDS82459

Canonical transcript exons

ENST00000394295 — 13 exons

Exon	Start	End
ENSE00001129960	69825456	69827112
ENSE00003468799	69804533	69804627
ENSE00003489992	69807906	69807996
ENSE00003516531	69819280	69819338
ENSE00003533742	69806385	69806498
ENSE00003574586	69820699	69820821
ENSE00003583997	69788054	69788141
ENSE00003600288	69781520	69781574
ENSE00003604986	69810594	69810673
ENSE00003689118	69818599	69818694
ENSE00003691277	69816101	69816194
ENSE00003691757	69812653	69812709
ENSE00003846637	69742134	69742175

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 99.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 65.5365 / max 1933.6366, expressed in 1820 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
20769	49.1242	1796
20768	12.2319	1711
20765	1.6436	1039
20762	0.9692	591
20761	0.8934	475
20767	0.4704	246
20766	0.1549	47
20770	0.0254	12
20763	0.0236	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	99.93	gold quality
gall bladder	UBERON:0002110	99.68	gold quality
jejunal mucosa	UBERON:0000399	99.48	gold quality
duodenum	UBERON:0002114	99.34	gold quality
body of pancreas	UBERON:0001150	99.28	gold quality
pancreas	UBERON:0001264	99.16	gold quality
ileal mucosa	UBERON:0000331	99.13	gold quality
islet of Langerhans	UBERON:0000006	99.07	gold quality
bronchial epithelial cell	CL:0002328	98.96	gold quality
colonic mucosa	UBERON:0000317	98.72	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.63	gold quality
tendon of biceps brachii	UBERON:0008188	98.59	gold quality
germinal epithelium of ovary	UBERON:0001304	98.46	gold quality
epithelium of bronchus	UBERON:0002031	98.46	gold quality
visceral pleura	UBERON:0002401	98.46	gold quality
choroid plexus epithelium	UBERON:0003911	98.40	gold quality
epithelial cell of pancreas	CL:0000083	98.32	gold quality
calcaneal tendon	UBERON:0003701	98.31	gold quality
bronchus	UBERON:0002185	98.30	gold quality
parietal pleura	UBERON:0002400	97.98	gold quality
pleura	UBERON:0000977	97.95	gold quality
pylorus	UBERON:0001166	97.92	gold quality
synovial joint	UBERON:0002217	97.91	gold quality
rectum	UBERON:0001052	97.87	gold quality
tendon	UBERON:0000043	97.84	gold quality
palpebral conjunctiva	UBERON:0001812	97.82	gold quality
placenta	UBERON:0001987	97.82	gold quality
mammalian vulva	UBERON:0000997	97.76	gold quality
urethra	UBERON:0000057	97.72	gold quality
skin of hip	UBERON:0001554	97.70	gold quality

Single-cell (SCXA)

Detected in 18 experiment(s), a significant marker in 17.

Experiment	Marker?	Max mean expression
E-MTAB-8495	yes	6487.38
E-GEOD-81547	yes	5115.20
E-MTAB-5061	yes	4461.58
E-GEOD-130473	yes	3881.02
E-GEOD-83139	yes	2957.40
E-MTAB-10553	yes	2691.27
E-HCAD-9	yes	2366.91
E-ENAD-27	yes	1799.63
E-CURD-98	yes	922.62
E-HCAD-10	yes	451.90
E-MTAB-8410	yes	46.06
E-MTAB-6701	yes	23.58
E-CURD-119	yes	18.87
E-CURD-114	yes	10.36
E-MTAB-6678	yes	8.40

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

73 targeting ANXA4, 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-3662	99.99	73.82	5684
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-8076	99.78	68.52	1170
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-6505-5P	99.73	69.25	1595

Literature-anchored findings (GeneRIF, showing 36)

• annexin IV plays an important role in the morphological diversification and dissemination of the clear cell renal cell carcinoma (PMID:15145526)
• This work provides mechanistic insight into how annexin A4 may regulate plasma membrane protein function. (PMID:16687573)
• ANXA4 transcription and translation are regulated by progesterone. ANXA4 may be important in regulating ion and water transport across the endometrial epithelium. (PMID:16954445)
• There were no significant differences in plasma annexin IV levels between women with and without antiphospholipid antibodies (PMID:17363042)
• analysis of translocation and assembly at the plasma membrane and the nuclear envelope (PMID:18164291)
• Enhanced expression of Annexin A4 is associated with clear cell carcinoma of the ovary (PMID:19598262)
• The overexpression of Annexin IV may be an ovarian CCC-specific molecular marker. (PMID:19955935)
• Annexin A4 differentially modulates the NF-kappaB signaling pathway, depending on its interactions with p50 and the intracellular Ca(2+) ion level. (PMID:20237821)
• Expression of ANXs was different in histologic subtypes of penile carcinomas. Strong expression of ANX AI and ANX AIV in the invasion front seems to indicate a higher risk of lymph node metastasis. (PMID:20602103)
• In an Alzheimer model, transgenic mice overexpressing mutant human amyloid precursor protein (APP) show a significant increase of annexin A5 in the brain cortex but not in other organs, including liver, kidney, lung, and intestine. (PMID:20648654)
• that H3K4 tri- and dimethylation play an important role and that JARID1A is the histone-demethylating enzyme responsible for removal of this mark (PMID:21348943)
• ANXA1 and, to a lesser extent, ANXA4 were detected on late but not early apoptotic HeLa cells. (PMID:22056994)
• Eight ANXA4 polymorphisms are significantly associated with the risk of aspirin-exacerbated respiratory disease. (PMID:22847161)
• Lower expression of annexin A4 during window of implantation in infertile patients with endometriosis might be associated with the decrease of endometrial receptivity. (PMID:22883517)
• suggest that ANXA4 triggers a signaling cascade, leading to increased epithelial cell proliferation, ultimately promoting carcinogenesis (PMID:22970268)
• This study showed that overexpression and nuclear localization of annexin A4 are related to chemoresistance and poor survival in patients with serous papillary ovarian carcinomas. (PMID:23290009)
• enhanced expression of Anx A4 confers platinum resistance by promoting efflux of platinum drugs via ATP7A. (PMID:24150977)
• Fhit delocalizes annexin A4 from plasma membrane to cytosol and sensitizes lung cancer cells to paclitaxel. (PMID:24223161)
• These findings indicate that the calcium-binding site in the ANXA4 repeat induces chemoresistance to the platinum-based drug by elevating the intracellular chloride concentration. (PMID:25277200)
• Data shows that CYTB and ANXA4 overexpression may be involved in carcinogenesis and histopathological differentiation of ovarian clear cell carcinoma and suggest they may serve as a potential diagnostic biomarkers. (PMID:25633807)
• these results suggest that AnxA4 is a novel direct negative regulator of AC5, adding a new facet to the functions of annexins. (PMID:26023182)
• role of annexin A4 in cancer (PMID:26048190)
• High ANXA4 expression is associated with metastasis of hepatocellular carcinoma. (PMID:26779633)
• Upregulation and nuclear translocation of ANXA4 have been observed in the progression of colorectal cancer and ovarian serous carcinoma. Knockdown of ANXA4 attenuated migration in ovarian cancer and breast cancer cells. In contrast, knockdown of ANXA4 increased susceptibility to platinum in ovarian cancer and malignant mesothelioma cells. Review. (PMID:27100483)
• Detecting ANXA2 and ANXA4 expression may aid the evaluation of cervical carcinoma prognosis. (PMID:27402115)
• Study identifies ANXA4 and FLNA as up-regulated in buccal squamous cell carcinoma arising from oral submucous fibrosis. (PMID:27485544)
• Taken together, these data indicate that up-regulation of ANXA4 leads to activation of the NF-kappaB pathway and its target genes in a feedback regulatory mechanism via the p65 subunit, resulting in tumor growth in GBC. (PMID:27491820)
• annexin A4 can be regarded as an important molecular marker in triple-negative breast cancer prognosis. (PMID:27650619)
• Annexin A4 binds to artificial membranes and generates curvature force initiated from free edges, whereas annexin A6 induces constriction force. (PMID:29158488)
• ANXA4 expression was increased at both the mRNA and protein level in the drugresistant ovarian cancer cells, and ANXA4 contained a Lewis(y) structure. ANXA4 overexpression can abnormally activate signaling pathways and regulate the expression of a numbers of factors, forming a positive feedback loop to induce the chemoresistance of ovarian cancer cells. (PMID:30066907)
• Bioinformatics analysis predicted that annexin A4 was a potential target gene of miR-203. Next, luciferase reporter assay confirmed that miR-203 could directly target annexin A4. (PMID:30837034)
• GSK3beta-Ikaros-ANXA4 signaling inhibits high-glucose-induced fibroblast migration. (PMID:32807499)
• Clinical Significance of Annexin A4 as a Biomarker in the Early Diagnosis of Hepatocellular Carcinoma. (PMID:32986366)
• p53 and ANXA4/NFkappaB p50 complexes regulate cell proliferation, apoptosis and tumor progression in ovarian clear cell carcinoma. (PMID:33125094)
• Membrane-cytoplasm translocation of annexin A4 is involved in the metastasis of colorectal carcinoma. (PMID:33761465)
• Evidence of an Annexin A4 mediated plasma membrane repair response to biomechanical strain associated with glaucoma pathogenesis. (PMID:35862065)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	anxa4	ENSDARG00000036456
mus_musculus	Anxa4	ENSMUSG00000029994
rattus_norvegicus	Anxa4	ENSRNOG00000018159
drosophila_melanogaster	AnxB9	FBGN0000083
drosophila_melanogaster	AnxB11	FBGN0030749

Paralogs (12): ANXA13 (ENSG00000104537), ANXA10 (ENSG00000109511), ANXA11 (ENSG00000122359), ANXA1 (ENSG00000135046), ANXA7 (ENSG00000138279), ANXA3 (ENSG00000138772), ANXA9 (ENSG00000143412), ANXA5 (ENSG00000164111), ANXA2 (ENSG00000182718), ANXA6 (ENSG00000197043), ANXA8L1 (ENSG00000264230), ANXA8 (ENSG00000265190)

Protein

Protein identifiers

Annexin A4 — P09525 (reviewed: P09525)

Alternative names: 35-beta calcimedin, Annexin IV, Annexin-4, Carbohydrate-binding protein p33/p41, Chromobindin-4, Endonexin I, Lipocortin IV, P32.5, PP4-X, Placental anticoagulant protein II, Protein II

All UniProt accessions (5): A0A0U1RRE7, A0A1Y8EKW3, B4E1S2, P09525, Q6P452

UniProt curated annotations — full annotation on UniProt →

Function. Calcium/phospholipid-binding protein which promotes membrane fusion and is involved in exocytosis.

Subcellular location. Zymogen granule membrane.

Domain organisation. A pair of annexin repeats may form one binding site for calcium and phospholipid.

Miscellaneous. Seems to bind one calcium ion with high affinity.

Similarity. Belongs to the annexin family.

Isoforms (3)

UniProt ID	Names	Canonical?
P09525-1	1	yes
P09525-2	2
P09525-3	3

RefSeq proteins (5): NP_001144, NP_001307627, NP_001307629, NP_001307631, NP_001352425 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001464	Annexin	Family
IPR002391	ANX4	Family
IPR018252	Annexin_repeat_CS	Conserved_site
IPR018502	Annexin_repeat	Repeat
IPR037104	Annexin_sf	Homologous_superfamily

Pfam: PF00191

UniProt features (43 total): helix 20, modified residue 6, strand 4, repeat 4, turn 3, splice variant 2, initiator methionine 1, chain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
9GA6	X-RAY DIFFRACTION	1.27
9GA7	X-RAY DIFFRACTION	1.45
9GA8	X-RAY DIFFRACTION	1.5
2ZOC	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P09525-F1	96.84	0.96

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): 293, 300, 2, 7, 12, 213

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 394 (showing top): FLECHNER_PBL_KIDNEY_TRANSPLANT_REJECTED_VS_OK_UP, GOBP_EPITHELIUM_DEVELOPMENT, KOBAYASHI_EGFR_SIGNALING_24HR_UP, GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_RESPONSE_TO_PEPTIDE, GOCC_SECRETORY_GRANULE, LFA1_Q6, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOCC_CELL_SURFACE, GOBP_NEGATIVE_REGULATION_OF_TUMOR_NECROSIS_FACTOR_MEDIATED_SIGNALING_PATHWAY, GGGTGGRR_PAX4_03, BOYLAN_MULTIPLE_MYELOMA_D_DN, GRANDVAUX_IRF3_TARGETS_DN, GOLDRATH_ANTIGEN_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION

GO Biological Process (9): negative regulation of transcription by RNA polymerase II (GO:0000122), signal transduction (GO:0007165), Notch signaling pathway (GO:0007219), negative regulation of tumor necrosis factor-mediated signaling pathway (GO:0010804), epithelial cell differentiation (GO:0030855), negative regulation of interleukin-8 production (GO:0032717), negative regulation of apoptotic process (GO:0043066), negative regulation of canonical NF-kappaB signal transduction (GO:0043124), negative regulation of coagulation (GO:0050819)

GO Molecular Function (9): phosphatidylserine binding (GO:0001786), phospholipase inhibitor activity (GO:0004859), calcium ion binding (GO:0005509), calcium-dependent phospholipid binding (GO:0005544), identical protein binding (GO:0042802), calcium-dependent protein binding (GO:0048306), NF-kappaB binding (GO:0051059), transcription regulator inhibitor activity (GO:0140416), protein binding (GO:0005515)

GO Cellular Component (12): nucleus (GO:0005634), cytoplasm (GO:0005737), plasma membrane (GO:0005886), cell surface (GO:0009986), vesicle membrane (GO:0012506), extracellular matrix (GO:0031012), nuclear membrane (GO:0031965), zymogen granule membrane (GO:0042589), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
phospholipid binding	2
protein binding	2
organelle membrane	2
cytoplasm	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell surface receptor signaling pathway	1
negative regulation of cytokine-mediated signaling pathway	1
regulation of tumor necrosis factor-mediated signaling pathway	1
tumor necrosis factor-mediated signaling pathway	1
cell differentiation	1
epithelium development	1
negative regulation of cytokine production	1
interleukin-8 production	1
regulation of interleukin-8 production	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
negative regulation of intracellular signal transduction	1
coagulation	1
regulation of coagulation	1
negative regulation of multicellular organismal process	1
anion binding	1
modified amino acid binding	1
glycerophospholipase activity	1
lipase inhibitor activity	1
metal ion binding	1
calcium ion binding	1
RNA polymerase II-specific DNA-binding transcription factor binding	1
regulation of gene expression	1
transcription regulator activity	1

Protein interactions and networks

STRING

1338 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANXA4	CCR5	P51681	790
ANXA4	S100A10	P08206	768
ANXA4	ANXA6	P08133	686
ANXA4	ACTG1	P02571	678
ANXA4	F3	P13726	603
ANXA4	ACTB	P02570	587
ANXA4	CD248	Q9HCU0	569
ANXA4	RBP2	P50120	542
ANXA4	S100A6	P06703	526
ANXA4	CRABP2	P29373	507
ANXA4	AHSG	P02765	506
ANXA4	CXCR4	P30991	505
ANXA4	CTSB	P07858	444
ANXA4	ALB	P02768	436
ANXA4	WDR1	O75083	436

IntAct

70 interactions, top by confidence:

A	B	Type	Score
PADI4	ANXA4	psi-mi:“MI:0915”(physical association)	0.720
ANXA4	PADI4	psi-mi:“MI:0915”(physical association)	0.720
ANXA4	BDNF	psi-mi:“MI:0915”(physical association)	0.560
CASP6	ANXA4	psi-mi:“MI:0915”(physical association)	0.560
ANXA4	CRYAB	psi-mi:“MI:0915”(physical association)	0.560
ANXA4	FKBP1A	psi-mi:“MI:0915”(physical association)	0.560
ANXA4	LAMP2	psi-mi:“MI:0915”(physical association)	0.560
RAN	ANXA4	psi-mi:“MI:0915”(physical association)	0.560
ANXA4	SARS1	psi-mi:“MI:0915”(physical association)	0.560
DNALI1	ANXA4	psi-mi:“MI:0915”(physical association)	0.560
KLF11	ANXA4	psi-mi:“MI:0915”(physical association)	0.560
DNAJB6	ANXA4	psi-mi:“MI:0915”(physical association)	0.560
PRPF40A	ANXA4	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (62): PADI4 (Two-hybrid), ANXA4 (Affinity Capture-MS), ANXA4 (Co-fractionation), ANXA4 (Reconstituted Complex), ANXA4 (Proximity Label-MS), SF3A3 (Affinity Capture-MS), ANXA4 (Affinity Capture-RNA), ANXA4 (Proximity Label-MS), ANXA4 (Affinity Capture-MS), ANXA4 (Affinity Capture-MS), RAB11FIP5 (Co-fractionation), ANXA4 (Two-hybrid), ANXA4 (Affinity Capture-MS), ANXA4 (Affinity Capture-MS), PDIA3 (Proximity Label-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 47 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
protein folding	5	12.3×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	39
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2368 predictions. Top by Δscore:

Variant	Effect	Δscore
2:69804529:CCAG:C	acceptor_loss	1.0000
2:69804531:A:AG	acceptor_gain	1.0000
2:69804531:A:T	acceptor_loss	1.0000
2:69804531:AG:A	acceptor_gain	1.0000
2:69804532:G:GC	acceptor_gain	1.0000
2:69804532:GG:G	acceptor_gain	1.0000
2:69804532:GGC:G	acceptor_gain	1.0000
2:69804532:GGCA:G	acceptor_gain	1.0000
2:69804532:GGCAC:G	acceptor_gain	1.0000
2:69804623:GCAGG:G	donor_gain	1.0000
2:69804626:GG:G	donor_gain	1.0000
2:69804626:GGGTA:G	donor_loss	1.0000
2:69804627:GG:G	donor_gain	1.0000
2:69804627:GGT:G	donor_loss	1.0000
2:69804628:G:GG	donor_gain	1.0000
2:69804628:G:T	donor_gain	1.0000
2:69804676:G:GT	donor_gain	1.0000
2:69806379:TTGCA:T	acceptor_loss	1.0000
2:69806381:GCAG:G	acceptor_loss	1.0000
2:69806382:CA:C	acceptor_loss	1.0000
2:69806383:A:AC	acceptor_loss	1.0000
2:69806383:A:AG	acceptor_gain	1.0000
2:69806384:G:GG	acceptor_gain	1.0000
2:69807992:GCAGC:G	donor_gain	1.0000
2:69807995:GC:G	donor_gain	1.0000
2:69810592:A:AG	acceptor_gain	1.0000
2:69810593:G:GG	acceptor_gain	1.0000
2:69810593:GA:G	acceptor_gain	1.0000
2:69810671:GCT:G	donor_gain	1.0000
2:69810674:G:GG	donor_gain	1.0000

AlphaMissense

2103 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000016989 (2:69813718 A>G), RS1000028386 (2:69692008 C>A,T), RS1000051225 (2:69813452 T>A), RS1000068325 (2:69654586 T>C), RS1000071288 (2:69726824 C>A), RS1000074272 (2:69644345 T>C), RS1000084965 (2:69752087 T>A), RS1000092664 (2:69725131 C>G), RS1000093660 (2:69805174 G>A,C,T), RS1000121710 (2:69726452 A>G), RS1000126040 (2:69743124 A>C,G), RS1000163764 (2:69679698 G>C), RS1000184951 (2:69656732 T>G), RS1000242107 (2:69656992 A>G,T), RS1000262913 (2:69698715 C>T)

Disease associations

OMIM: gene MIM:106491 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001841_13	Palmitoleic acid (16:1n-7) levels	5.000000e-06
GCST004297_2	Atrial fibrillation	1.000000e-10
GCST006414_66	Atrial fibrillation	1.000000e-16

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066970 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression	7
bisphenol A	affects expression, decreases expression, increases expression	4
trichostatin A	affects cotreatment, increases expression	3
Acetaminophen	decreases expression, increases expression	3
Air Pollutants	decreases expression, increases expression, increases abundance	3
perfluorooctanoic acid	decreases expression, increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
Resveratrol	affects cotreatment, decreases expression, increases expression	2
Caffeine	affects phosphorylation, decreases expression	2
Cisplatin	decreases response to substance, increases reaction, affects localization, affects cotreatment, increases expression	2
Copper	affects binding	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Tretinoin	increases expression	2
Cyclosporine	decreases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
bufotalin	decreases expression	1
methylmercuric chloride	decreases expression	1
potassium perchlorate	increases expression	1
pyrogallol 1,3-dimethyl ether	affects localization, increases expression, affects cotreatment	1
arsenite	affects binding, increases reaction	1
methylparaben	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	increases methylation	1
epigallocatechin gallate	decreases expression	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
CHEMBL5650899	Binding	Binding affinity to human ANXA4 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)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery