ANXA2R

Summary

ANXA2R (annexin A2 receptor, HGNC:33463) is a protein-coding gene on chromosome 5p12, encoding Annexin-2 receptor (Q3ZCQ2). May act as a receptor for annexin II on marrow stromal cells to induce osteoclast formation.

Predicted to enable signaling receptor activity.

Source: NCBI Gene 389289 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 37 total — 4 pathogenic
• MANE Select transcript: NM_001014279

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33463
Approved symbol	ANXA2R
Name	annexin A2 receptor
Location	5p12
Locus type	gene with protein product
Status	Approved
Aliases	AXIIR
Ensembl gene	ENSG00000177721
Ensembl biotype	protein_coding
OMIM	611296
Entrez	389289

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000314890, ENST00000616064

RefSeq mRNA: 2 — MANE Select: NM_001014279 NM_001014279, NM_001382352

CCDS: CCDS34153

Canonical transcript exons

ENST00000616064 — 1 exons

Exon	Start	End
ENSE00003720498	43039371	43040319

Expression profiles

Bgee: expression breadth ubiquitous, 174 present calls, max score 90.34.

FANTOM5 (CAGE): breadth broad, TPM avg 5.3736 / max 200.5405, expressed in 872 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
61535	2.0170	207
61536	1.7377	375
61534	0.8240	255
61541	0.7949	368

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	90.34	gold quality
blood	UBERON:0000178	82.69	gold quality
lymph node	UBERON:0000029	82.61	gold quality
spleen	UBERON:0002106	82.27	gold quality
vermiform appendix	UBERON:0001154	79.20	gold quality
ileal mucosa	UBERON:0000331	77.94	gold quality
bone marrow	UBERON:0002371	77.54	gold quality
leukocyte	CL:0000738	77.09	gold quality
bone marrow cell	CL:0002092	76.31	gold quality
monocyte	CL:0000576	76.12	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.92	silver quality
thymus	UBERON:0002370	75.67	gold quality
tendon of biceps brachii	UBERON:0008188	74.47	silver quality
small intestine Peyer’s patch	UBERON:0003454	73.78	gold quality
omental fat pad	UBERON:0010414	71.74	gold quality
peritoneum	UBERON:0002358	71.66	gold quality
small intestine	UBERON:0002108	71.52	gold quality
adipose tissue of abdominal region	UBERON:0007808	71.33	gold quality
stromal cell of endometrium	CL:0002255	70.98	gold quality
caecum	UBERON:0001153	70.86	gold quality
subcutaneous adipose tissue	UBERON:0002190	70.76	gold quality
right uterine tube	UBERON:0001302	70.67	gold quality
ectocervix	UBERON:0012249	70.10	gold quality
tibial nerve	UBERON:0001323	69.78	gold quality
right coronary artery	UBERON:0001625	69.57	gold quality
upper lobe of left lung	UBERON:0008952	69.48	gold quality
tibialis anterior	UBERON:0001385	68.97	silver quality
endocervix	UBERON:0000458	68.84	gold quality
vagina	UBERON:0000996	68.80	gold quality
oviduct epithelium	UBERON:0004804	68.78	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	3.72
E-ANND-3	no	2.86

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

35 targeting ANXA2R, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-888-3P	99.53	69.77	1057
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-8065	99.19	70.38	1289
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-6830-5P	99.01	68.73	1884
HSA-MIR-4738-3P	98.98	67.98	1846
HSA-MIR-520G-3P	98.91	67.38	1914
HSA-MIR-520H	98.91	67.38	1914
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-12114	98.70	63.45	730
HSA-MIR-4703-5P	98.53	70.13	1645
HSA-MIR-3942-5P	98.52	69.51	1517
HSA-MIR-561-5P	98.25	68.13	1365

Literature-anchored findings (GeneRIF, showing 7)

• analysis of the annexin II receptor on human marrow stromal cells (PMID:16895901)
• annexin II and its receptor axis play a central role in prostate cancer metastasis, and prostate cancer utilizes the hematopoietic stem cell homing mechanisms to gain access to the niche. (PMID:18636554)
• Results show that AXII and AXIIR play important roles in multiple myeloma (MM) and that targeting the AXII/AXIIR axis may be a novel therapeutic approach for MM. (PMID:22223826)
• AXIIR acts as a novel inducer of apoptosis in human cells, partially through activating Caspase-8. (PMID:23640736)
• these subsequent effects might be via suppressing the expression of matrix metalloproteinase 2 and matrix metalloproteinase 9. … AXIIR participates in angiogenesis, and may be a potential therapeutic target for angiogenesis related diseases (PMID:25633185)
• Data highlighted the crucial role of AXIIR in reducing Mum2C cell viability through inducing apoptosis, while autophagy played a protective role in this process. (PMID:27183438)
• Overexpression of AX2R significantly inhibited cell proliferation, migration and tube formation in both types of endothelial cells and increased the expression of KLF2, mediating VEGF and VEGFR2. (PMID:29694949)

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Annexin-2 receptor — Q3ZCQ2 (reviewed: Q3ZCQ2)

Alternative names: Annexin II receptor

All UniProt accessions (1): Q3ZCQ2

UniProt curated annotations — full annotation on UniProt →

Function. May act as a receptor for annexin II on marrow stromal cells to induce osteoclast formation.

Tissue specificity. Widely expressed. Highly expressed in lymphocytes. Expressed in both resting CD4(+) and CD8(+) T-cells.

RefSeq proteins (2): NP_001014301, NP_001369281 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR031449	ANXA2R	Family

Pfam: PF15721

UniProt features (5 total): sequence variant 2, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q3ZCQ2-F1	55.65	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 70 (showing top): BENPORATH_ES_WITH_H3K27ME3, RICKMAN_TUMOR_DIFFERENTIATED_MODERATELY_VS_POORLY_UP, ACEVEDO_LIVER_CANCER_UP, BOSCO_TH1_CYTOTOXIC_MODULE, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, ATF5_TARGET_GENES, BARX1_TARGET_GENES, CHAMP1_TARGET_GENES, FOXN3_TARGET_GENES, GLI4_TARGET_GENES, HDAC4_TARGET_GENES, HES2_TARGET_GENES, HOXB4_TARGET_GENES, ID2_TARGET_GENES, MIER1_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (2): signaling receptor activity (GO:0038023), protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
molecular transducer activity	1
binding	1

Protein interactions and networks

STRING

142 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANXA2R	ANXA2	P07355	997
ANXA2R	S100A10	P08206	733
ANXA2R	CXCL12	P48061	527
ANXA2R	PLAT	P00750	520
ANXA2R	AXL	P30530	486
ANXA2R	CXCR4	P30991	441
ANXA2R	GAS6	Q14393	391
ANXA2R	TMLHE	Q9NVH6	356
ANXA2R	HNRNPA0	Q13151	322
ANXA2R	GPATCH11	Q8N954	322
ANXA2R	IL6	P05231	320
ANXA2R	CD8A	P01732	317
ANXA2R	C4orf33	Q8N1A6	305
ANXA2R	BBX	Q8WY36	305
ANXA2R	CD4	P01730	304

IntAct

4 interactions, top by confidence:

A	B	Type	Score
ANXA2R	CNOT1	psi-mi:“MI:0914”(association)	0.540
CNOT1	ANXA2R	psi-mi:“MI:0915”(physical association)	0.540
CNOT1	ANXA2R	psi-mi:“MI:0403”(colocalization)	0.540

BioGRID (8): CNOT1 (Affinity Capture-MS), CNOT3 (Affinity Capture-MS), CNOT6L (Affinity Capture-MS), CNOT7 (Affinity Capture-MS), RQCD1 (Affinity Capture-MS), TNKS1BP1 (Affinity Capture-MS), ANXA2R (Affinity Capture-MS), ANXA2R (Affinity Capture-RNA)

ESM2 similar proteins: A0A1B0GVZ6, A0A1W2PR82, A0A286YDK6, A2A9F4, A2VE02, A5D7I0, A6H7B4, A6NE82, A6NEV1, A6NJB7, A6NJI1, A6NJJ6, A6QP24, A6QPM6, A8MZG2, D3ZAQ5, D4AAA5, O94850, O95873, P0C7X2, P50617, P70339, Q0P5M0, Q2KIL8, Q2KIS6, Q3UN58, Q3ZCQ2, Q5JPB2, Q5M844, Q5VZ46, Q6AY88, Q6GQX2, Q6NZ36, Q6ZW13, Q76NI1, Q7TNS8, Q80TS7, Q86YN6, Q8C1M2, Q8K2F3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	32
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1458418	NC_000005.9:g.(?42688972)(44388784_?)del	Pathogenic
1705919	GRCh37/hg19 5p13.2-11(chr5:36053583-46389339)x3	Pathogenic
58092	GRCh38/hg38 5p13.2-12(chr5:35700480-45260029)x3	Pathogenic
58093	GRCh38/hg38 5p13.2-q11.1(chr5:36374107-51103841)x3	Pathogenic

SpliceAI

285 predictions. Top by Δscore:

Variant	Effect	Δscore
5:43039917:GTACT:G	acceptor_gain	0.7700
5:43039916:AGTAC:A	acceptor_gain	0.7600
5:43039912:T:A	donor_gain	0.7000
5:43039643:T:TA	donor_gain	0.6900
5:43040233:TAGA:T	donor_gain	0.6900
5:43040234:AGAA:A	donor_gain	0.6900
5:43039871:C:CC	acceptor_gain	0.6800
5:43040305:G:C	donor_gain	0.6700
5:43039964:A:AC	donor_gain	0.6600
5:43039965:C:CC	donor_gain	0.6600
5:43039817:ACTCC:A	acceptor_gain	0.6500
5:43039919:ACTGG:A	acceptor_gain	0.6300
5:43039918:TACTG:T	acceptor_gain	0.5900
5:43039920:C:A	acceptor_gain	0.5900
5:43039632:AGACC:A	donor_loss	0.5800
5:43039633:GACC:G	donor_loss	0.5800
5:43039634:A:T	donor_loss	0.5800
5:43039635:C:CA	donor_loss	0.5800
5:43039868:GGG:G	acceptor_gain	0.5800
5:43039868:GGGCT:G	acceptor_loss	0.5800
5:43039869:GGCTG:G	acceptor_loss	0.5800
5:43039870:GCTGG:G	acceptor_loss	0.5800
5:43039871:CTG:C	acceptor_loss	0.5800
5:43039818:C:A	acceptor_gain	0.5700
5:43039872:T:G	acceptor_loss	0.5700
5:43039920:C:CC	acceptor_gain	0.5700
5:43039636:C:G	donor_loss	0.5500
5:43039873:G:C	acceptor_loss	0.5400
5:43039582:CGG:C	acceptor_gain	0.5100
5:43039821:C:CT	acceptor_gain	0.5100

AlphaMissense

1242 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:43039926:A:C	Y41D	0.891
5:43040032:A:C	F5L	0.873
5:43040032:A:T	F5L	0.873
5:43040034:A:G	F5L	0.873
5:43040017:C:A	K10N	0.862
5:43040017:C:G	K10N	0.862
5:43039561:G:C	F162L	0.834
5:43039561:G:T	F162L	0.834
5:43039563:A:G	F162L	0.834
5:43039926:A:T	Y41N	0.818
5:43039774:G:C	F91L	0.817
5:43039774:G:T	F91L	0.817
5:43039776:A:G	F91L	0.817
5:43039926:A:G	Y41H	0.816
5:43039870:G:C	S59R	0.807
5:43039870:G:T	S59R	0.807
5:43039872:T:G	S59R	0.807
5:43039925:T:G	Y41S	0.793
5:43039530:C:G	G173R	0.790
5:43039861:C:A	W62C	0.789
5:43039861:C:G	W62C	0.789
5:43040007:C:G	D14H	0.774
5:43039516:G:C	F177L	0.769
5:43039516:G:T	F177L	0.769
5:43039518:A:G	F177L	0.769
5:43039925:T:C	Y41C	0.767
5:43040008:C:A	W13C	0.758
5:43040008:C:G	W13C	0.758
5:43039529:C:T	G173D	0.750
5:43039934:A:T	L38H	0.739

dbSNP variants (sampled 300 via entrez): RS1000180747 (5:43042463 AAAAG>A), RS1000524274 (5:43039957 T>C), RS1001091892 (5:43041100 C>T), RS1001274196 (5:43043456 T>C), RS1001409958 (5:43043245 G>A,C), RS1002947846 (5:43042251 G>A), RS1003042753 (5:43042083 G>C), RS1004268361 (5:43041837 G>A), RS1004690313 (5:43043513 T>A), RS1004785081 (5:43043307 G>A,C), RS1005125694 (5:43044403 A>C), RS1005360374 (5:43040779 A>G), RS1006037902 (5:43043305 G>A), RS1006393321 (5:43042588 T>G), RS1007260978 (5:43044400 C>T)

Disease associations

OMIM: gene MIM:611296 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): developmental and epileptic encephalopathy (MONDO:0100620)

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	decreases expression	1
sodium arsenite	increases abundance, affects cotreatment, decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
di-n-butylphosphoric acid	affects expression	1
ICG 001	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
jinfukang	increases expression	1
Temozolomide	decreases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Arsenicals	increases methylation	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Catechin	decreases expression, affects cotreatment	1
Drugs, Chinese Herbal	decreases expression	1
Manganese	increases abundance, affects cotreatment, decreases expression	1
Nickel	increases expression	1
Niclosamide	increases expression	1
Aflatoxin B1	decreases methylation	1
Asbestos, Serpentine	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03347526	PHASE3	SUSPENDED	A Novel Approach to Infantile Spasms
NCT03421496	PHASE3	TERMINATED	A Study to Assess Cannabidiol Oral Solution With Vigabatrin as Initial Therapy in Participants With Infantile Spasms
NCT06719141	PHASE3	RECRUITING	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathies (DEE)
NCT06908226	PHASE3	ENROLLING_BY_INVITATION	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathy (DEE)
NCT04289467	PHASE2	RECRUITING	Treatment of Refractory Infantile Spasms With Fenfluramine
NCT05626634	PHASE2	COMPLETED	Open-label, Long-term Safety Study of LP352 in Subjects With Developmental and Epileptic Encephalopathy
NCT04727970	PHASE1	COMPLETED	Tricaprilin Infantile Spasms Pilot Study
NCT06700811	PHASE1	RECRUITING	Ketogenic Diet for Prevention of Epileptic Spasms in Infantile Onset Genetic Epilepsies
NCT03876444	PHASE2/PHASE3	UNKNOWN	Intravenous Methylprednisolone Versus Oral Prednisolone for Infantile Spasms
NCT05279118	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Ketogenic Diet vs ACTH for the Treatment of Children With West Syndrome
NCT05364021	PHASE1/PHASE2	COMPLETED	Study to Investigate LP352 in Subjects With Developmental and Epileptic Encephalopathies
NCT06983158	PHASE1/PHASE2	SUSPENDED	A Clinical Trial of CAP-002 Gene Therapy in Pediatric Patients With Syntaxin-Binding Protein 1 (STXBP1) Encephalopathy
NCT04937062	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	Phenylbutyrate for Monogenetic Developmental and Epileptic Encephalopathy
NCT04302116	Not specified	RECRUITING	Vigabatrin With High Dose Prednisolone Combination Therapy vs Vigabatrin Alone for Infantile Spasm
NCT05538936	Not specified	COMPLETED	The Effect of Spa and Massage on Babies on Colic Symptoms
NCT06149663	Not specified	AVAILABLE	Intermediate-Size Expanded Access Protocol (EAP) for LP352
NCT06266234	Not specified	RECRUITING	Characterization by Automated System on Infantile Spasmes
NCT06380192	Not specified	RECRUITING	Developmental and Epileptic Encephalopathy of Genetic Etiology: Natural History Through Reuse of Clinical Data
NCT07396883	Not specified	NOT_YET_RECRUITING	Developmental and Epileptic Encephalopathies Diagnosed Via Long-read Genome Sequencing
NCT07413211	Not specified	RECRUITING	Genetic Developmental and Epileptic Encephalopathy Natural History Study for Clinical Trial Readiness
NCT07531511	Not specified	NOT_YET_RECRUITING	SLC6A1-NDD Prospective Longitudinal Natural History Study
NCT07585643	Not specified	NOT_YET_RECRUITING	IBIS - Investigating Reliability of BIS and SEDLINE Monitoring in Children With Developmental and Epileptic Encephalopathies (DEE).