ANXA7

Summary

ANXA7 (annexin A7, HGNC:545) is a protein-coding gene on chromosome 10q22.2, encoding Annexin A7 (P20073). Calcium/phospholipid-binding protein which promotes membrane fusion and is involved in exocytosis.

Annexin VII is a member of the annexin family of calcium-dependent phospholipid binding proteins.The Annexin VII gene contains 14 exons and spans approximately 34 kb of DNA. An alternatively spliced cassette exon results in two mRNA transcripts of 2.0 and 2.4 kb which are predicted to generate two protein isoforms differing in their N-terminal domain. The alternative splicing event is tissue specific and the mRNA containing the cassette exon is prevalent in brain, heart and skeletal muscle. The transcripts also differ in their 3’-non coding regions by the use of two alternative poly(A) signals. Annexin VII encodes a protein with a molecular weight of approximately 51 kDa with a unique, highly hydrophobic N-terminal domain of 167 amino acids and a conserved C-terminal region of 299 amino acids. The latter domain is composed of alternating hydrophobic and hydrophilic segments. Structural analysis of the protein suggests that Annexin VII is a membrane binding protein with diverse properties, including voltage-sensitive calcium channel activity, ion selectivity and membrane fusion.

Source: NCBI Gene 310 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 85 total — 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_001156

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:545
Approved symbol	ANXA7
Name	annexin A7
Location	10q22.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000138279
Ensembl biotype	protein_coding
OMIM	186360
Entrez	310

Gene structure

Transcript identifiers

Ensembl transcripts: 48 — 46 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000372919, ENST00000372921, ENST00000394847, ENST00000463788, ENST00000492380, ENST00000892948, ENST00000892949, ENST00000892950, ENST00000892951, ENST00000892952, ENST00000892953, ENST00000892954, ENST00000892955, ENST00000892956, ENST00000892957, ENST00000892958, ENST00000892959, ENST00000892960, ENST00000892961, ENST00000892962, ENST00000892963, ENST00000892964, ENST00000892965, ENST00000892966, ENST00000892967, ENST00000892968, ENST00000892969, ENST00000930446, ENST00000930447, ENST00000930448, ENST00000930449, ENST00000930450, ENST00000961262, ENST00000961263, ENST00000961264, ENST00000961265, ENST00000961266, ENST00000961267, ENST00000961268, ENST00000961269, ENST00000961270, ENST00000961271, ENST00000961272, ENST00000961273, ENST00000961274, ENST00000961275, ENST00000961276, ENST00000961277

RefSeq mRNA: 4 — MANE Select: NM_001156 NM_001156, NM_001320879, NM_001320880, NM_004034

CCDS: CCDS7325, CCDS7326

Canonical transcript exons

ENST00000372921 — 13 exons

Exon	Start	End
ENSE00001102255	73379879	73379954
ENSE00001102259	73378911	73379023
ENSE00001102268	73380031	73380201
ENSE00001102270	73383175	73383345
ENSE00001459061	73400803	73400857
ENSE00003476886	73396519	73396583
ENSE00003538818	73398181	73398385
ENSE00003552632	73387689	73387783
ENSE00003616785	73388312	73388414
ENSE00003666215	73383577	73383690
ENSE00003673501	73397164	73397274
ENSE00003704541	73375101	73376217
ENSE00003849770	73414012	73414058

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 41.2929 / max 299.4776, expressed in 1820 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
110059	40.5319	1820
110054	0.3671	136
110055	0.2102	74
110058	0.1153	35
110056	0.0433	18
110057	0.0252	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	99.21	gold quality
islet of Langerhans	UBERON:0000006	98.86	gold quality
secondary oocyte	CL:0000655	98.61	gold quality
type B pancreatic cell	CL:0000169	98.32	gold quality
tendon	UBERON:0000043	98.30	gold quality
cauda epididymis	UBERON:0004360	98.27	gold quality
calcaneal tendon	UBERON:0003701	98.17	gold quality
gastrocnemius	UBERON:0001388	98.10	gold quality
muscle of leg	UBERON:0001383	98.07	gold quality
right coronary artery	UBERON:0001625	98.00	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.00	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.97	gold quality
tendon of biceps brachii	UBERON:0008188	97.96	gold quality
bronchial epithelial cell	CL:0002328	97.85	gold quality
popliteal artery	UBERON:0002250	97.85	gold quality
tibial artery	UBERON:0007610	97.85	gold quality
caput epididymis	UBERON:0004358	97.84	gold quality
muscle organ	UBERON:0001630	97.83	gold quality
synovial joint	UBERON:0002217	97.83	gold quality
gingival epithelium	UBERON:0001949	97.81	gold quality
descending thoracic aorta	UBERON:0002345	97.77	gold quality
nephron tubule	UBERON:0001231	97.74	gold quality
aorta	UBERON:0000947	97.69	gold quality
corpus epididymis	UBERON:0004359	97.67	gold quality
seminal vesicle	UBERON:0000998	97.63	gold quality
germinal epithelium of ovary	UBERON:0001304	97.61	gold quality
gingiva	UBERON:0001828	97.61	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.56	gold quality
epithelium of bronchus	UBERON:0002031	97.54	gold quality
heart right ventricle	UBERON:0002080	97.53	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-8498	yes	10.26
E-GEOD-93593	yes	8.16
E-GEOD-125970	yes	6.72
E-HCAD-11	yes	6.47
E-MTAB-10137	no	377.33
E-MTAB-6058	no	228.58
E-CURD-112	no	2.60
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
ITGB4	Repression

miRNA regulators (miRDB)

75 targeting ANXA7, 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-3163	100.00	77.23	8605
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4639-5P	99.81	67.37	1028
HSA-MIR-489-3P	99.80	66.46	839
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-6832-5P	99.58	64.82	1132
HSA-MIR-7844-5P	99.55	68.56	1428
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-3923	99.52	69.21	446
HSA-MIR-4761-5P	99.51	66.69	804
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-6833-5P	99.50	68.93	1161

Literature-anchored findings (GeneRIF, showing 35)

• synexin mediates galectin-3 translocation to the perinuclear mitochondrial membranes, where it regulates mitochondrial integrity critical for apoptosis regulation. (PMID:11839755)
• the calcium-dependent membrane fusion activity of annexin 7 in vitro is further potentiated by the combined addition of guanine nucleotide and protein kinase C (PMID:11994295)
• The penta-EF-hand domain of ALG-2 interacts with the amino-terminal domain of annexin VII in a Ca2+-dependent manner. (PMID:12445460)
• ANXA7 and p53 can distinctly regulate LOX transcription that is potentially relevant to the arachidonic acid -mediated cell growth control in tumor suppression. (PMID:17018618)
• Annexin VII was present in reticulocytes but was then lost as the cells matured. A different pattern was found in band 3-deficient samples: annexin VII was in fact present in both mature and immature red cell membranes. (PMID:17112522)
• Decreased ANXA7 expression was mostly associated with high invasive potential in multiple tumors. The lymph node metastases from different sites (including prostate and breast) had decreased ANXA7 expression. (PMID:17708571)
• correlation between ANXA7 expression and cell differentiation of gastric cancer was observed (PMID:18449914)
• Haploinsufficiency of the tumor suppressor ANXA7 due to monosomy of chromosome 10 provides a clinically relevant mechanism to augment EGFR signaling in glioblastomas beyond that resulting from amplification of the EGFR gene. (PMID:19602687)
• A7 and A11 have sequence repeats that form novel structures, called YP pro-beta helices, that are characterized by an ability to interact with one another (PMID:20093729)
• a multi-hnRNP complex can be responsible for aberrant ANXA7 transcription and splicing, thereby affecting ANXA7 expression pattern and tumor suppressor function in prostate cancer. (PMID:20190808)
• The study indicates that stomatin, sorcin, and synexin are echinophilic membrane components that mainly locate outside GM1 rafts in the human erythrocyte membrane. (PMID:20858460)
• Annexin A7 may be involved in the pathophysiology of refractory epilepsy and may play a role in developing and maintaining the epilepsy (PMID:21432772)
• ANXA7, PPP3CB, DNAJC9, and ZMYND17 genes are potential candidate genes for schizophrenia, especially in patients with deficits in sustained attention and executive function. (PMID:21531385)
• The study data have demonstrated the pathogenic roles and therapeutic significance of Anx7 in RA for the first time. (PMID:21586441)
• The present observations demonstrate that enhanced eryptosis of annexin7 deficient cells is paralleled by increased adhesion of erythrocytes to the vascular wall, an effect, which may impact on microcirculation during ischemia. (PMID:23437197)
• We have found ANXA7 to be functioning like a tumour promoter in HepG2 human hepatocellular carcinoma cells (PMID:23582794)
• by identifying ABO as an unprecedented modulator of ANXA7 as well as GCA and LC3 as interacting proteins of ANXA7, we demonstrated the possible mechanisms how ANXA7 regulates autophagy for the first time. (PMID:23651924)
• Both annexin A7 and integrin beta4 were essential for small molecule, 6-amino-2, 3-dihydro-3-hydroxymethyl-1, 4-benzoxazine-induced autophagy. (PMID:24007983)
• Annexin A7 expression was able to inhibit HCC lymph node metastasis, whereas knockdown of Annexin A7 expression significantly induced HCC metastasis to local lymph nodes. (PMID:24188284)
• The role of distinct SGK1/FOXO3A-associated regulation in p53 versus ANXA7 responses were elucidated and proposed that aberrant SGK1 could affect reciprocal SGK1-FOXO3A-Akt regulation. (PMID:24864229)
• Alternative ANXA7 splicing was present in precursor cells, suggesting that glioblastoma cells inherit the trait from a potential tumor-initiating ancestor and that these cells exploit this the through accumulation of mutations that enhance EGFR signaling. (PMID:24865424)
• miRNA-155 promoted the proliferation of prostate cancer cells by regulating ANX7 expression levels. (PMID:25339368)
• High annexin A7 expression is associated with poor differentiation in gastric cancer patients, and it may be a predictor for lymphatic metastasis. (PMID:25400735)
• data reveal that high UBE3C expression contributes to glioma progression by ubiquitination and degradation of ANXA7, and thus presents a novel and promising target for glioma therapy. (PMID:26067607)
• Up-regulation of ANXA7-GTPase tumor suppressor reverses tumorigenesis. (Review) (PMID:27807828)
• Study demonstrates that annexin A7 protein has an important role in gastric cancer. Silencing the expression of ANXA7 in vitro and in vivo induces the apoptosis of BGC823 gastric cancer cells and, importantly, inhibits the growth of tumor xenografts in mice. (PMID:28176245)
• ANXA7 was downregulated in breast cancer cells and higher expression of ANXA7 was associated with better prognosis of breast cancer patients. (PMID:29893423)
• Overexpression of ANXA7 enhances eucalyptol cytotoxicity in prostate cancer cell lines (PMID:29970503)
• Annexin A7 has a prognostic role in prostate cancer progression (PMID:30321230)
• Meanwhile, the key biomarkers of cell metastasis E-cadherin expression increased while MMP-9 decreased.we found that ANXA7 played its role via MAPK/ERK pathway. ANXA7 might involve in the development of hepatocellular carcinoma and act as an oncogene which might be a potential therapeutic target for treatment. (PMID:30347600)
• Annexin A7 is required for ESCRT III-mediated plasma membrane repair. (PMID:31040365)
• ANXA7 regulates trophoblast proliferation and apoptosis in preeclampsia. (PMID:31446642)
• Knockdown of annexin VII enhances nasopharyngeal carcinoma cell radiosensitivity in vivo and in vitro. (PMID:31958076)
• ANXA7 promotes the cell cycle, proliferation and cell adhesion-mediated drug resistance of multiple myeloma cells by up-regulating CDC5L. (PMID:32526706)
• AnnexinA7 promotes epithelial-mesenchymal transition by interacting with Sorcin and contributes to aggressiveness in hepatocellular carcinoma. (PMID:34716295)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Anxa7	ENSMUSG00000021814
rattus_norvegicus	Anxa7	ENSRNOG00000007136
drosophila_melanogaster	AnxB9	FBGN0000083
drosophila_melanogaster	AnxB11	FBGN0030749

Paralogs (12): ANXA13 (ENSG00000104537), ANXA10 (ENSG00000109511), ANXA11 (ENSG00000122359), ANXA1 (ENSG00000135046), ANXA3 (ENSG00000138772), ANXA9 (ENSG00000143412), ANXA5 (ENSG00000164111), ANXA2 (ENSG00000182718), ANXA4 (ENSG00000196975), ANXA6 (ENSG00000197043), ANXA8L1 (ENSG00000264230), ANXA8 (ENSG00000265190)

Protein

Protein identifiers

Annexin A7 — P20073 (reviewed: P20073)

Alternative names: Annexin VII, Annexin-7, Synexin

All UniProt accessions (2): B9ZVT2, P20073

UniProt curated annotations — full annotation on UniProt →

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

Subunit / interactions. Interacts with PDCD6.

Tissue specificity. Isoform 1 is expressed in brain, heart and skeletal muscle. Isoform 2 is more abundant in liver, lung, kidney, spleen, fibroblasts and placenta.

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

Similarity. Belongs to the annexin family.

Isoforms (2)

UniProt ID	Names	Canonical?
P20073-1	1, Annexin VIIb	yes
P20073-2	2, Annexin VIIa

RefSeq proteins (4): NP_001147, NP_001307808, NP_001307809, NP_004025 (=MANE)

Domains & families (InterPro)

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

Pfam: PF00191

UniProt features (14 total): repeat 4, region of interest 4, compositionally biased region 2, chain 1, modified residue 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8W5S	X-RAY DIFFRACTION	2.12

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P20073-F1	77.67	0.66

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 (1): 233

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 194 (showing top): AP1_01, GOBP_EPITHELIUM_DEVELOPMENT, GOCC_SECRETORY_GRANULE, AAGCCAT_MIR135A_MIR135B, DITTMER_PTHLH_TARGETS_UP, MORF_HDAC2, GGGTGGRR_PAX4_03, AP1_Q4_01, ROZANOV_MMP14_TARGETS_UP, GOTZMANN_EPITHELIAL_TO_MESENCHYMAL_TRANSITION_DN, TGANTCA_AP1_C, SCHLOSSER_SERUM_RESPONSE_DN, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_UP, SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_UP, FLECHNER_BIOPSY_KIDNEY_TRANSPLANT_REJECTED_VS_OK_DN

GO Biological Process (6): autophagy (GO:0006914), negative regulation of gene expression (GO:0010629), epithelial cell differentiation (GO:0030855), response to calcium ion (GO:0051592), membrane fusion (GO:0061025), response to phorbol 13-acetate 12-myristate (GO:1904627)

GO Molecular Function (7): phosphatidylserine binding (GO:0001786), RNA binding (GO:0003723), integrin binding (GO:0005178), calcium ion binding (GO:0005509), calcium-dependent phospholipid binding (GO:0005544), calcium-dependent protein binding (GO:0048306), protein binding (GO:0005515)

GO Cellular Component (9): nucleus (GO:0005634), cytoplasm (GO:0005737), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), vesicle membrane (GO:0012506), membrane (GO:0016020), extracellular matrix (GO:0031012), extracellular exosome (GO:0070062), chromaffin granule membrane (GO:0042584)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phospholipid binding	2
cellular anatomical structure	2
organelle membrane	2
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
cell differentiation	1
epithelium development	1
response to metal ion	1
membrane organization	1
response to lipid	1
response to alcohol	1
response to ketone	1
anion binding	1
modified amino acid binding	1
nucleic acid binding	1
signaling receptor binding	1
protein-containing complex binding	1
cell adhesion molecule binding	1
metal ion binding	1
calcium ion binding	1
protein binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
vesicle	1
external encapsulating structure	1
extracellular vesicle	1
secretory granule membrane	1
chromaffin granule	1

Protein interactions and networks

STRING

1184 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANXA7	LGALS3	P17931	929
ANXA7	SRI	P30626	830
ANXA7	VPS29	Q9UBQ0	778
ANXA7	VPS26A	O75436	752
ANXA7	VPS35	Q96QK1	738
ANXA7	RACK1	P25388	618
ANXA7	GTPBP4	Q9BZE4	590
ANXA7	SNX1	Q13596	570
ANXA7	BAG4	O95429	542
ANXA7	PEF1	Q9UBV8	522
ANXA7	TSG101	Q99816	516
ANXA7	SNX2	P82862	507
ANXA7	SNX6	Q9UNH7	505
ANXA7	PRDX6	P30041	503
ANXA7	SNX5	Q9Y5X3	479

IntAct

150 interactions, top by confidence:

A	B	Type	Score
HRAS	RAF1	psi-mi:“MI:0914”(association)	0.980
NRAS	RAF1	psi-mi:“MI:0914”(association)	0.930
	MYL12B	psi-mi:“MI:0914”(association)	0.460
ANXA7	SRI	psi-mi:“MI:0407”(direct interaction)	0.440
SRI	ANXA7	psi-mi:“MI:0407”(direct interaction)	0.440
ANXA7	PDCD6	psi-mi:“MI:0915”(physical association)	0.400
ANXA7	MOB1A	psi-mi:“MI:0915”(physical association)	0.400
SPG11	ANXA7	psi-mi:“MI:0915”(physical association)	0.370
A1BG	ANXA7	psi-mi:“MI:0915”(physical association)	0.370
ANXA7	A2M	psi-mi:“MI:0915”(physical association)	0.370
ANXA7	ACTB	psi-mi:“MI:0915”(physical association)	0.370
ACTL6B	ANXA7	psi-mi:“MI:0915”(physical association)	0.370
ANXA7	ADAMTS10	psi-mi:“MI:0915”(physical association)	0.370
ANGPT2	ANXA7	psi-mi:“MI:0915”(physical association)	0.370
ANXA7	APLP1	psi-mi:“MI:0915”(physical association)	0.370
ANXA7	ATP5F1B	psi-mi:“MI:0915”(physical association)	0.370
ANXA7	ATP6V1A	psi-mi:“MI:0915”(physical association)	0.370
ANXA7	ATXN3	psi-mi:“MI:0915”(physical association)	0.370
BAG6	ANXA7	psi-mi:“MI:0915”(physical association)	0.370
ANXA7	ERG28	psi-mi:“MI:0915”(physical association)	0.370
LRIF1	ANXA7	psi-mi:“MI:0915”(physical association)	0.370
RBM48	ANXA7	psi-mi:“MI:0915”(physical association)	0.370
CCDC90B	ANXA7	psi-mi:“MI:0915”(physical association)	0.370
ANXA7	CCT7	psi-mi:“MI:0915”(physical association)	0.370
CDK4	ANXA7	psi-mi:“MI:0915”(physical association)	0.370
ANXA7	CENPB	psi-mi:“MI:0915”(physical association)	0.370
CHGB	ANXA7	psi-mi:“MI:0915”(physical association)	0.370
CLEC3B	ANXA7	psi-mi:“MI:0915”(physical association)	0.370
COL11A2	ANXA7	psi-mi:“MI:0915”(physical association)	0.370
COL4A2	ANXA7	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (207): ANXA7 (Affinity Capture-RNA), ANXA7 (Affinity Capture-RNA), ANXA7 (Co-fractionation), ANXA7 (Co-fractionation), ANXA7 (Co-fractionation), ANXA7 (Co-fractionation), C11orf54 (Co-fractionation), PCBP1 (Co-fractionation), TKT (Co-fractionation), TTN (Co-fractionation), ANXA7 (Affinity Capture-Western), UBE3C (Affinity Capture-Western), ANXA7 (Affinity Capture-MS), ANXA7 (Affinity Capture-MS), ANXA7 (Affinity Capture-MS)

ESM2 similar proteins: A1CEK6, A2QW93, B5X370, C1BZR1, J9VS56, O55201, P0CO44, P0CO45, P0CR70, P0CR71, P13230, P20072, P20073, P24639, P27214, P30599, P33477, P34122, P50995, P91277, P97384, Q07076, Q0CJU8, Q0U6X7, Q2QY10, Q3B8H2, Q4LBC7, Q4LBC8, Q4P0H7, Q4R5L5, Q4WXV6, Q52DM9, Q5BBL4, Q5PQ53, Q5ZI08, Q641Z8, Q6CFT4, Q6DC93, Q6DFR0, Q75B43

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 148 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
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	5	18.2×	3e-03
Prefoldin mediated transfer of substrate to CCT/TriC	5	17.6×	3e-03
Signaling by high-kinase activity BRAF mutants	5	14.2×	4e-03
Chaperonin-mediated protein folding	5	13.4×	4e-03
Aggrephagy	6	13.3×	3e-03
MAP2K and MAPK activation	5	12.8×	4e-03
Ovarian tumor domain proteases	5	12.4×	4e-03
Signaling by RAF1 mutants	5	12.4×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	70
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3065768	NM_001156.5(ANXA7):c.1089+1G>T	Likely pathogenic

SpliceAI

1827 predictions. Top by Δscore:

Variant	Effect	Δscore
10:73376214:CAAT:C	acceptor_gain	1.0000
10:73376217:TC:T	acceptor_loss	1.0000
10:73376218:C:CA	acceptor_loss	1.0000
10:73376218:C:CC	acceptor_gain	1.0000
10:73376219:T:G	acceptor_loss	1.0000
10:73378905:CCTCA:C	donor_loss	1.0000
10:73378906:CTCA:C	donor_loss	1.0000
10:73378907:TCACC:T	donor_loss	1.0000
10:73378908:CACCT:C	donor_loss	1.0000
10:73378909:ACCTC:A	donor_loss	1.0000
10:73378910:C:CA	donor_loss	1.0000
10:73378910:CCTCA:C	donor_gain	1.0000
10:73379873:TCTTA:T	donor_loss	1.0000
10:73379874:CTTAC:C	donor_loss	1.0000
10:73379875:TTACA:T	donor_loss	1.0000
10:73379876:TA:T	donor_loss	1.0000
10:73379877:A:AC	donor_gain	1.0000
10:73379877:A:C	donor_loss	1.0000
10:73379878:C:CG	donor_gain	1.0000
10:73379878:CAG:C	donor_gain	1.0000
10:73379878:CAGAT:C	donor_gain	1.0000
10:73379951:CCAT:C	acceptor_gain	1.0000
10:73379952:CATC:C	acceptor_gain	1.0000
10:73379955:C:CC	acceptor_gain	1.0000
10:73380027:ATAC:A	donor_gain	1.0000
10:73380029:AC:A	donor_gain	1.0000
10:73380030:CC:C	donor_gain	1.0000
10:73380060:G:C	donor_gain	1.0000
10:73380155:T:TA	donor_gain	1.0000
10:73380197:TTTCC:T	acceptor_gain	1.0000

AlphaMissense

2997 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:73383674:A:G	L239P	0.999
10:73387707:A:C	F227L	0.999
10:73387707:A:T	F227L	0.999
10:73387709:A:G	F227L	0.999
10:73387728:C:A	R220S	0.999
10:73387728:C:G	R220S	0.999
10:73387783:C:T	G202E	0.999
10:73380059:A:G	L376P	0.998
10:73380094:A:C	F364L	0.998
10:73380094:A:T	F364L	0.998
10:73380096:A:G	F364L	0.998
10:73380132:C:G	A352P	0.998
10:73380140:A:G	L349P	0.998
10:73380150:C:G	A346P	0.998
10:73380195:G:T	R331S	0.998
10:73383197:C:G	R321P	0.998
10:73383686:A:G	L235S	0.998
10:73387729:C:G	R220T	0.998
10:73387765:A:T	I208N	0.998
10:73388335:A:G	L194P	0.998
10:73388335:A:T	L194H	0.998
10:73388345:C:G	A191P	0.998
10:73380039:A:C	Y383D	0.997
10:73380095:A:G	F364S	0.997
10:73380140:A:T	L349H	0.997
10:73380149:G:T	A346D	0.997
10:73383191:A:G	L323P	0.997
10:73383674:A:T	L239H	0.997
10:73387708:A:G	F227S	0.997
10:73387744:C:G	R215P	0.997

dbSNP variants (sampled 300 via entrez): RS1000062632 (10:73391965 A>C), RS1000093329 (10:73392149 G>A,C), RS1000246590 (10:73399867 C>T), RS1000470000 (10:73405729 C>T), RS1000500686 (10:73395644 G>A), RS1000631291 (10:73412357 T>A,G), RS1000665464 (10:73374679 G>A), RS1000667873 (10:73404749 C>T), RS1000695288 (10:73385395 A>T), RS1000739690 (10:73404986 C>T), RS1000849685 (10:73378727 T>C), RS1000868978 (10:73408167 A>T), RS1000948971 (10:73403055 C>G), RS1001044776 (10:73385016 AT>A), RS1001087645 (10:73379060 T>C)

Disease associations

OMIM: gene MIM:186360 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002938_13	Copper levels	1.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066944 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.16	Kd	69.72	nM	CHEMBL5653589
7.16	ED50	69.72	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 4 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	2147860: Binding affinity to human ANXA7 incubated for 45 mins by Kinobead based pull down assay	kd	0.0697	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression	3
Cadmium Chloride	decreases expression, increases abundance, increases expression	3
bisphenol S	affects expression, increases expression	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
Silicon Dioxide	decreases expression	2
Particulate Matter	decreases reaction, increases expression, decreases expression, increases abundance	2
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization, increases expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
manganese chloride	increases expression, affects cotreatment, increases abundance	1
deguelin	increases expression	1
K 7174	increases expression	1
bisphenol B	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases reaction, increases expression	1
picoxystrobin	increases expression	1
bisphenol AF	increases expression	1
Vorinostat	increases expression	1
Acetaminophen	decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Vehicle Emissions	decreases reaction, increases expression	1
Benztropine	increases expression	1
Cadmium	increases abundance, increases expression	1
Catechin	affects cotreatment, increases expression	1
Furaldehyde	affects cotreatment, affects localization, decreases expression, increases expression	1
Ivermectin	decreases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Ozone	affects expression, increases abundance	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
CHEMBL5650902	Binding	Binding affinity to human ANXA7 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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