ANP32A

Summary

ANP32A (acidic nuclear phosphoprotein 32 family member A, HGNC:13233) is a protein-coding gene on chromosome 15q23, encoding Acidic leucine-rich nuclear phosphoprotein 32 family member A (P39687). Multifunctional protein that is involved in the regulation of many processes including tumor suppression, apoptosis, cell cycle progression or transcription.

Enables RNA binding activity. Involved in nucleocytoplasmic transport. Located in endoplasmic reticulum; nucleus; and perinuclear region of cytoplasm.

Source: NCBI Gene 8125 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 20 total
• Druggable target: yes
• MANE Select transcript: NM_006305

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13233
Approved symbol	ANP32A
Name	acidic nuclear phosphoprotein 32 family member A
Location	15q23
Locus type	gene with protein product
Status	Approved
Aliases	LANP, PP32, I1PP2A, PHAPI, MAPM, mapmodulin
Ensembl gene	ENSG00000140350
Ensembl biotype	protein_coding
OMIM	600832
Entrez	8125

Gene structure

Transcript identifiers

Ensembl transcripts: 39 — 30 protein_coding, 4 protein_coding_CDS_not_defined, 4 retained_intron, 1 nonsense_mediated_decay

ENST00000267918, ENST00000409628, ENST00000465139, ENST00000480858, ENST00000483221, ENST00000483551, ENST00000486054, ENST00000495420, ENST00000495764, ENST00000560303, ENST00000561430, ENST00000882106, ENST00000882107, ENST00000882108, ENST00000882109, ENST00000882110, ENST00000882111, ENST00000882112, ENST00000882113, ENST00000923059, ENST00000923060, ENST00000923061, ENST00000923062, ENST00000923063, ENST00000923064, ENST00000923065, ENST00000923066, ENST00000923067, ENST00000923068, ENST00000923069, ENST00000923070, ENST00000923071, ENST00000923072, ENST00000923073, ENST00000923074, ENST00000923075, ENST00000923076, ENST00000923077, ENST00000967540

RefSeq mRNA: 1 — MANE Select: NM_006305 NM_006305

CCDS: CCDS45292

Canonical transcript exons

ENST00000465139 — 7 exons

Exon	Start	End
ENSE00001929076	68778535	68780142
ENSE00002540651	68820698	68820895
ENSE00003496435	68782956	68783053
ENSE00003509325	68787413	68787535
ENSE00003527508	68780410	68780473
ENSE00003572937	68784397	68784595
ENSE00003624046	68787770	68787919

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.41.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 57.4730 / max 1073.5701, expressed in 1821 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
150677	33.7367	1816
150675	8.2529	1666
150674	6.8889	1589
150676	4.9561	1579
150678	2.2865	1241
150671	0.6796	320
150670	0.3871	191
150665	0.2852	111

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	99.41	gold quality
cortical plate	UBERON:0005343	99.29	gold quality
embryo	UBERON:0000922	99.14	gold quality
ventricular zone	UBERON:0003053	99.08	gold quality
monocyte	CL:0000576	99.03	gold quality
mononuclear cell	CL:0000842	98.96	gold quality
leukocyte	CL:0000738	98.91	gold quality
paraflocculus	UBERON:0005351	98.79	gold quality
middle frontal gyrus	UBERON:0002702	98.41	gold quality
rectum	UBERON:0001052	97.98	gold quality
blood	UBERON:0000178	97.92	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.87	gold quality
inferior vagus X ganglion	UBERON:0005363	97.86	gold quality
granulocyte	CL:0000094	97.81	gold quality
bone marrow	UBERON:0002371	97.70	gold quality
vermiform appendix	UBERON:0001154	97.69	gold quality
lymph node	UBERON:0000029	97.65	gold quality
spinal cord	UBERON:0002240	97.55	gold quality
caecum	UBERON:0001153	97.47	gold quality
mucosa of transverse colon	UBERON:0004991	97.45	gold quality
tendon of biceps brachii	UBERON:0008188	97.44	gold quality
subthalamic nucleus	UBERON:0001906	97.38	gold quality
cerebellum	UBERON:0002037	97.37	gold quality
cerebellar hemisphere	UBERON:0002245	97.37	gold quality
spleen	UBERON:0002106	97.29	gold quality
cerebellar cortex	UBERON:0002129	97.29	gold quality
cranial nerve II	UBERON:0000941	97.21	gold quality
right atrium auricular region	UBERON:0006631	97.12	gold quality
frontal pole	UBERON:0002795	97.01	gold quality
medial globus pallidus	UBERON:0002477	97.00	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-9221	yes	23.89
E-MTAB-10042	yes	9.96
E-GEOD-36552	no	196.61
E-MTAB-7303	no	95.51
E-GEOD-93593	no	6.70
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1, LHX3, SPI1, STAT5A, STAT5B

miRNA regulators (miRDB)

83 targeting ANP32A, 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-6798-5P	100.00	65.77	699
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-1305	99.91	71.43	3443

Literature-anchored findings (GeneRIF, showing 40)

• Regulation of histone acetylation and transcription by nuclear protein pp32, a subunit of the INHAT complex. (PMID:11830591)
• regulatory roles of oncoprotein ProT and tumor suppressor PHAP in apoptosis (PMID:12522243)
• LANP could play a key role in neuronal development and/or neurodegeneration by its interactions with microtubule associated proteins (PMID:12807913)
• Set/TAF-Ibeta and pp32 proteins have roles as transducers of chromatin signaling by integrating chromatin hypoacetylation and transcriptional repression (PMID:15136563)
• tyrosine phosphorylation of PHAPI is accompanied by the release of PP2A from association with PHAPI, allowing increased phosphatase activity of PP2A and consequent complete dephosphorylation of the ERK kinase, MEK1/2, by 10 min and of ERK1/2 by 60 min (PMID:15247276)
• We now show pp32 increases androgen receptor-mediated transcription and the retinoblastoma protein modulates this activity. (PMID:16009334)
• The ANP32A protein is characterizing as modulators of Wnt protein signaling of Axin-1. (PMID:16169070)
• pp32 plays a repressive role by inhibiting transcription and triggering apoptosis. (PMID:16341127)
• Immunoblot detection revealed that the inhibitor I1PP2A is expressed throughout the brain, including the hippocampus, temporal cortex, parietal cortex, subcortical nuclei and brain stem. (PMID:17266954)
• LANP and ATAXN1 interact in E4F-mediated transcriptional repression. (PMID:17557114)
• These results identify pp32/PHAPI as regulator of the apoptosis response of cancer cells in vitro and in vivo, and as a predictor of survival following chemotherapy for advanced non-small-cell lung cancer. (PMID:17962813)
• Results describe the solution structure of the evolutionarily conserved N-terminal leucine-rich repeat (LRR) domain of Anp32a and model its interactions with other proteins. (PMID:18410380)
• PHAPI, CAS, and Hsp70 function together to accelerate nucleotide exchange on Apaf-1 and prevent inactive Apaf-1/cytochrome c aggregation. (PMID:18439902)
• PHAPI/pp32 suppresses tumorigenesis by stimulating apoptosis. (PMID:19121999)
• ANP32A is involved in the pathogenesis of osteoarthritis of the hip. (PMID:19565487)
• Sphingosine interaction with acidic leucine-rich nuclear phosphoprotein-32A (ANP32A) regulates PP2A activity and cyclooxygenase (COX)-2 expression in human endothelial cells. (PMID:20558741)
• The HPPCn expression might be involved in the development of hepatocellular carcinoma and could be served as a promising biomarker. (PMID:20683644)
• Data provide evidence that the tumor suppressor function of pp32 can be attributed to its ability to disrupt HuR binding to target mRNAs encoding key proteins for cancer cell survival and drug efficacy. (PMID:21152064)
• MicroRNA-21 targets tumor suppressor genes ANP32A and SMARCA4. (PMID:21317927)
• pp32 interacted with STAT1 and STAT2 in an IFNB-dependent manner. (PMID:21325029)
• Demonstrate that HPPCn attenuated oxidative injury and fibrosis induced by ethanol feeding and that the SphK1/S1P/S1PRs signalling pathway contributes to this protective effect. (PMID:23839903)
• conformational analysis of the C-terminal transition state of the leucine-rich repeat domain of PP32 (PMID:25902505)
• High-resolution crystal structure of the leucine-rich repeat domain of the human tumour suppressor PP32A (ANP32A) has been reported. (PMID:26057796)
• Host-derived proteins pp32 and APRIL interact with a free form of influenza virus RNA-dependent RNA polymerase and preferentially upregulates viral RNA synthesis rather than cRNA synthesis. (PMID:26512887)
• ANP32A represents an essential host partner co-opted to support influenza virus replication and is a candidate host target for novel antivirals (PMID:26738596)
• Results suggest that ANP32A is commonly increased in oral squamous cell carcinoma and ANP32A protein could act as a potential biomarker for prognosis assessment of oral cancer patients with lymph node metastasis. (PMID:26918356)
• ANP32A promoted CRC proliferation by inhibition of p38. (PMID:28731192)
• These data suggest compensatory mechanisms underlying viral Polymerase adaptation to host ANP32A independent of species-specific interactions. (PMID:28903035)
• Data show that PP32 and SET/TAF-Ibeta proteins block HAT1-mediated H4 acetylation. (PMID:28977641)
• According to the cellular function of the characterized targets of ProTalpha, and the evolution in the composition of the diverse ProTalpha-complexes when proliferation activity was reduced or apoptosis induced, leads to hypothesized that ProTalpha interactions might be related to the proliferation activity and control of the cell survival. (PMID:29106904)
• our study reveals that ANP32A dysregulation may be a critical factor contributing to acute megakaryoblastic leukemia (PMID:29269781)
• our data indicate that ANP32A is a novel regulator of histone H3 acetylation and promotes leukemogenesis. (PMID:29467488)
• PHAP1 expression is elevated in glioma patients, which may accelerate the proliferation of glioma cells by regulating the Akt/p27/stathmin pathway. (PMID:29667783)
• ANP32A/ATM axis discovered in cartilage is also present in brain and bone. (PMID:30209244)
• The C-terminal portion of ANP32A and the middle domains (residues 307-534) of PB2 were required for PB2-ANP32A interaction. (PMID:30666459)
• ANP32A and ANP32B from different species are powerful factors in the maintenance of viral polymerase activity. Human ANP32A and ANP32B contribute equally to support human influenza viral RNA replication. (PMID:30996088)
• Human ANP32A and ANP32B homologues both support function of human-adapted influenza polymerase but do not support efficient activity of avian IAV polymerase which requires avian ANP32A. (PMID:31159925)
• The contribution of minimal asparagine ladder from the leucine-rich repeat protein pp32 to stability is tested and lattice rigidity and hydrogen bond character is investigated. Point substitutions of the two ladder asparagines of pp32 are strongly destabilizing and decrease the cooperativity of unfolding. Asparagine side chains are held in a very rigid, nondynamic structure, making a significant contribution to stability. (PMID:31347358)
• ANP32A and ANP32B mediate the export of unspliced or partially spliced viral mRNA via interactions with Rev and CRM1. (PMID:31444273)
• ANP32A differentially regulates vRNA levels for species-specific effects on PB2 627E polymerase activity. (PMID:31608791)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	anp32a	ENSDARG00000006487
mus_musculus	Anp32a	ENSMUSG00000032249
rattus_norvegicus	Anp32a	ENSRNOG00000014846
rattus_norvegicus		ENSRNOG00000063773
drosophila_melanogaster	Mapmodulin	FBGN0034282
caenorhabditis_elegans	F33H2.3	WBGENE00009367
caenorhabditis_elegans		WBGENE00020588

Paralogs (3): ANP32B (ENSG00000136938), ANP32D (ENSG00000139223), ANP32E (ENSG00000143401)

Protein

Protein identifiers

Acidic leucine-rich nuclear phosphoprotein 32 family member A — P39687 (reviewed: P39687)

Alternative names: Acidic nuclear phosphoprotein pp32, Leucine-rich acidic nuclear protein, Mapmodulin, Potent heat-stable protein phosphatase 2A inhibitor I1PP2A, Putative HLA-DR-associated protein I

All UniProt accessions (4): P39687, A0A384P5U2, H0YN26, H7BZ09

UniProt curated annotations — full annotation on UniProt →

Function. Multifunctional protein that is involved in the regulation of many processes including tumor suppression, apoptosis, cell cycle progression or transcription. Promotes apoptosis by favouring the activation of caspase-9/CASP9 and allowing apoptosome formation. In addition, plays a role in the modulation of histone acetylation and transcription as part of the INHAT (inhibitor of histone acetyltransferases) complex. Inhibits the histone-acetyltranferase activity of EP300/CREBBP (CREB-binding protein) and EP300/CREBBP-associated factor by histone masking. Preferentially binds to unmodified histone H3 and sterically inhibiting its acetylation and phosphorylation leading to cell growth inhibition. Participates in other biochemical processes such as regulation of mRNA nuclear-to-cytoplasmic translocation and stability by its association with ELAVL1 (Hu-antigen R). Plays a role in E4F1-mediated transcriptional repression as well as inhibition of protein phosphatase 2A. (Microbial infection) Plays an essential role in influenza A, B and C viral genome replication. Mechanistically, mediates the assembly of the viral replicase asymmetric dimers composed of PB1, PB2 and PA via its N-terminal region. Also plays an essential role in foamy virus mRNA export from the nucleus.

Subunit / interactions. Component of the SET complex, composed of at least ANP32A, APEX1, HMGB2, NME1, SET and TREX1. Directly interacts with SET. Interacts with ATXN1/SCA1. Interacts with MAP1B. Interacts with ELAVL1. Part of the INHAT (inhibitor of histone acetyltransferases) complex. Interacts with E4F1. (Microbial infection) Interacts (via C-terminus) with influenza virus A protein PB2; this interaction promotes viral replication. (Microbial infection) Interacts (via C-terminus) with influenza virus B protein PB2; this interaction promotes viral replication. (Microbial infection) Interacts (via C-terminus) with influenza virus C protein PB2; this interaction promotes viral replication by bridging viral replicase dimers together.

Subcellular location. Nucleus. Cytoplasm. Endoplasmic reticulum.

Tissue specificity. Expressed in all tissues tested. Highly expressed in kidney and skeletal muscle, moderate levels of expression in brain, placenta and pancreas, and weakly expressed in lung. Found in all regions of the brain examined (amygdala, caudate nucleus, corpus callosum, hippocampus and thalamus), with highest levels in amygdala.

Post-translational modifications. Phosphorylated on serine residues, at least in part by casein kinase 2/CK2. The N-terminus is blocked. Some glutamate residues are glycylated by TTLL8. This modification occurs exclusively on glutamate residues and results in a glycine chain on the gamma-carboxyl group.

Similarity. Belongs to the ANP32 family.

RefSeq proteins (1): NP_006296* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001611	Leu-rich_rpt	Repeat
IPR003603	U2A’_phosphoprotein32A_C	Domain
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR045081	AN32	Family

Pfam: PF14580

UniProt features (35 total): helix 7, mutagenesis site 6, strand 5, repeat 4, modified residue 4, region of interest 3, compositionally biased region 2, chain 1, sequence conflict 1, turn 1, domain 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
4XOS	X-RAY DIFFRACTION	1.56
2JE0	X-RAY DIFFRACTION	2.4
2JE1	X-RAY DIFFRACTION	2.69
8RN0	ELECTRON MICROSCOPY	3.13
8RMR	ELECTRON MICROSCOPY	3.25
8RNB	ELECTRON MICROSCOPY	3.31
8RNC	ELECTRON MICROSCOPY	3.52
8RNA	ELECTRON MICROSCOPY	3.57
6XZQ	ELECTRON MICROSCOPY	3.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P39687-F1	79.69	0.61

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 (4): 15, 17, 158, 204

Mutagenesis-validated functional residues (6):

Position	Phenotype
158	complete loss of phosphorylation; when associated with a-204.
158	no loss of phosphorylation.
189	loss of interaction with influenza virus a pb2.
196	loss of interaction with influenza virus a pb2.
204	complete loss of phosphorylation; when associated with a-158.
204	no loss of phosphorylation.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-450520	HuR (ELAVL1) binds and stabilizes mRNA
R-HSA-450531	Regulation of mRNA stability by proteins that bind AU-rich elements
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 279 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, MORF_DNMT1, MYAATNNNNNNNGGC_UNKNOWN, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GCANCTGNY_MYOD_Q6, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, MORF_RRM1, MORF_HDAC1, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_DN, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN, MORF_HDAC2, CAGCTG_AP4_Q5, SP1_Q2_01

GO Biological Process (3): nucleocytoplasmic transport (GO:0006913), intracellular signal transduction (GO:0035556), regulation of apoptotic process (GO:0042981)

GO Molecular Function (3): RNA binding (GO:0003723), histone binding (GO:0042393), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), perinuclear region of cytoplasm (GO:0048471)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Regulation of mRNA stability by proteins that bind AU-rich elements	1
Metabolism of RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
intracellular anatomical structure	2
intracellular membrane-bounded organelle	2
cytoplasm	2
nuclear transport	1
signal transduction	1
apoptotic process	1
regulation of programmed cell death	1
nucleic acid binding	1
protein binding	1
binding	1
nuclear lumen	1
endomembrane system	1

Protein interactions and networks

STRING

1334 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANP32A	APEX1	P27695	995
ANP32A	SET	Q01105	991
ANP32A	NME1	P15531	978
ANP32A	ELAVL1	Q15717	904
ANP32A	PTMA	P06454	845
ANP32A	GZMA	P12544	841
ANP32A	XPO1	O14980	817
ANP32A	PPP2CA	P05323	784
ANP32A	MAP4	P27816	772
ANP32A	ATXN1	P54253	770
ANP32A	HMGB2	P26583	724
ANP32A	DEK	P35659	658
ANP32A	LGMN	Q99538	596
ANP32A	E4F1	Q66K89	594
ANP32A	ANP32B	P78458	586

IntAct

66 interactions, top by confidence:

A	B	Type	Score
KPNA6	RNMT	psi-mi:“MI:0914”(association)	0.800
KPNA1	TCERG1	psi-mi:“MI:0914”(association)	0.640
ANP32A	ATXN1	psi-mi:“MI:0915”(physical association)	0.560
ANP32A	E4F1	psi-mi:“MI:0403”(colocalization)	0.560
E4F1	ANP32A	psi-mi:“MI:0915”(physical association)	0.560
AXIN1	ANP32A	psi-mi:“MI:0915”(physical association)	0.510
	ANP32A	psi-mi:“MI:0915”(physical association)	0.500
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
ANP32A	CSNK2A1	psi-mi:“MI:0915”(physical association)	0.400
ANP32A	Ppp2ca	psi-mi:“MI:0915”(physical association)	0.400
Ppp2ca	ANP32A	psi-mi:“MI:0915”(physical association)	0.400
ANP32A	PPP2CA	psi-mi:“MI:0915”(physical association)	0.400
PCBP1	ANP32A	psi-mi:“MI:0915”(physical association)	0.370
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
JUN		psi-mi:“MI:0914”(association)	0.350
	TBKBP1	psi-mi:“MI:0914”(association)	0.350
VP24	SLC25A3	psi-mi:“MI:0914”(association)	0.350
VP24	PGRMC1	psi-mi:“MI:0914”(association)	0.350
DLD	NFKBIE	psi-mi:“MI:0914”(association)	0.350
SERPINE1	HSP90B1	psi-mi:“MI:0914”(association)	0.350
PB2	DNAJB6	psi-mi:“MI:0914”(association)	0.350
ARHGEF39	SEC16A	psi-mi:“MI:0914”(association)	0.350
DOCK8	IPO5	psi-mi:“MI:0914”(association)	0.350
Pik3r2	EDIL3	psi-mi:“MI:0914”(association)	0.350
HIRIP3	H2AX	psi-mi:“MI:0914”(association)	0.350
NEDD4	HMGB1P1	psi-mi:“MI:0914”(association)	0.350

BioGRID (198): AHCYL1 (Co-fractionation), ANP32A (Co-fractionation), ANP32A (Co-fractionation), ANP32A (Co-fractionation), ANP32A (Co-fractionation), ANP32A (Co-fractionation), ANP32B (Co-fractionation), ANP32E (Co-fractionation), DMAP1 (Co-fractionation), PAPPA (Co-fractionation), VPRBP (Co-fractionation), VPS72 (Co-fractionation), ANP32A (Affinity Capture-MS), ELAVL1 (Affinity Capture-Western), ANP32A (Proximity Label-MS)

ESM2 similar proteins: G3V9R8, O35381, O43423, O60812, O77768, O88978, P07910, P0DME0, P19600, P39687, P49911, P50503, P51122, P97822, Q01105, Q1RMR5, Q28XE2, Q32KP2, Q3SZC6, Q4KLJ8, Q4R3F0, Q5F4A3, Q5RA82, Q5REE1, Q5UAK0, Q5XIE0, Q5ZKT9, Q5ZLF0, Q5ZMN0, Q63945, Q64G17, Q6A1I3, Q6NUW5, Q6P1U7, Q6PAF6, Q7ZUP0, Q7ZY40, Q86X45, Q8AVC1, Q8HY67

Diamond homologs: O01615, O35381, O62220, O95626, P39687, P49911, P51122, P97822, Q28XE2, Q3SZC6, Q5F4A3, Q5XIE0, Q5ZMN0, Q64G17, Q6A1I3, Q6NUW5, Q6P1U7, Q6PAF6, Q6YSF3, Q7ZUP0, Q86QS6, Q8AVC1, Q8HY67, Q8ILI6, Q92688, Q9BTT0, Q9EST5, Q9EST6, Q9SCQ7, Q9V895, O43423, O88984, Q4P5F9, Q5BGW9, Q7Y180, Q7ZY40, Q9UBU9, Q9V4Q8, P34390, Q5Y2C3

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ANP32A	“up-regulates activity”	CASP9	binding
RB1	“down-regulates activity”	ANP32A	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 81 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
NLS-bearing protein import into nucleus	5	59.0×	1e-05
protein import into nucleus	6	12.7×	2e-03
response to endoplasmic reticulum stress	5	12.3×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	10
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1475 predictions. Top by Δscore:

Variant	Effect	Δscore
15:68780083:A:AC	donor_gain	1.0000
15:68780083:AGT:A	donor_gain	1.0000
15:68780084:G:C	donor_gain	1.0000
15:68780138:TTCTT:T	acceptor_gain	1.0000
15:68780140:CTT:C	acceptor_gain	1.0000
15:68780141:TT:T	acceptor_gain	1.0000
15:68780142:TC:T	acceptor_loss	1.0000
15:68780143:C:CC	acceptor_gain	1.0000
15:68780143:CTGGA:C	acceptor_loss	1.0000
15:68780144:T:A	acceptor_loss	1.0000
15:68780405:CATA:C	donor_loss	1.0000
15:68780406:ATAC:A	donor_loss	1.0000
15:68780407:TACCA:T	donor_loss	1.0000
15:68780408:A:C	donor_loss	1.0000
15:68780409:C:A	donor_loss	1.0000
15:68780409:CCA:C	donor_gain	1.0000
15:68780416:G:C	donor_gain	1.0000
15:68780430:T:TA	donor_gain	1.0000
15:68780469:TCCTC:T	acceptor_gain	1.0000
15:68780470:CCTCC:C	acceptor_gain	1.0000
15:68780471:CTC:C	acceptor_gain	1.0000
15:68780474:C:CC	acceptor_gain	1.0000
15:68780474:CT:C	acceptor_loss	1.0000
15:68782953:TA:T	donor_loss	1.0000
15:68782954:A:C	donor_loss	1.0000
15:68782954:ACCT:A	donor_gain	1.0000
15:68782955:CCTC:C	donor_gain	1.0000
15:68782957:T:TA	donor_gain	1.0000
15:68782972:ACGT:A	donor_gain	1.0000
15:68782973:CGTC:C	donor_gain	1.0000

AlphaMissense

1663 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:68784483:C:A	G147V	1.000
15:68784483:C:T	G147D	1.000
15:68784484:C:G	G147R	1.000
15:68784485:G:C	D146E	1.000
15:68784485:G:T	D146E	1.000
15:68784486:T:A	D146V	1.000
15:68784486:T:G	D146A	1.000
15:68784487:C:G	D146H	1.000
15:68784489:A:G	L145P	1.000
15:68784489:A:T	L145H	1.000
15:68784498:A:T	L142H	1.000
15:68784532:A:G	Y131H	1.000
15:68784554:G:C	C123W	1.000
15:68784555:C:A	C123F	1.000
15:68784555:C:T	C123Y	1.000
15:68784556:A:G	C123R	1.000
15:68784560:G:C	F121L	1.000
15:68784560:G:T	F121L	1.000
15:68784562:A:C	F121V	1.000
15:68784562:A:G	F121L	1.000
15:68784562:A:T	F121I	1.000
15:68784564:A:G	L120P	1.000
15:68784564:A:T	L120H	1.000
15:68784567:T:C	D119G	1.000
15:68784567:T:G	D119A	1.000
15:68784570:A:G	L118S	1.000
15:68784579:A:G	L115P	1.000
15:68784579:A:T	L115H	1.000
15:68787441:A:G	I100T	1.000
15:68787446:G:C	N98K	1.000

dbSNP variants (sampled 300 via entrez): RS1000079547 (15:68800980 G>A), RS1000181224 (15:68818749 C>G,T), RS1000220833 (15:68801124 G>C), RS1000263178 (15:68800580 T>C), RS1000291463 (15:68801452 G>A), RS1000346303 (15:68821265 G>A), RS1000454020 (15:68807105 C>T), RS1000491225 (15:68782478 T>A,C), RS1000504749 (15:68806082 A>C,G), RS1000601494 (15:68816038 C>G), RS1000605813 (15:68799429 G>C), RS1000634166 (15:68811528 G>C), RS1000775377 (15:68810685 C>T), RS1000780731 (15:68821115 G>C), RS1000916073 (15:68817233 C>A)

Disease associations

OMIM: gene MIM:600832 | 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

1 associations (top):

Study	Trait	p-value
GCST001089_6	Esophageal cancer	1.000000e-11

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): CHEMBL4295758 (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
5.64	Kd	2285	nM	CHEMBL3752910
5.64	ED50	2285	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 6 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-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147851: Binding affinity to human ANP32A incubated for 45 mins by Kinobead based pull down assay	kd	2.2852	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, decreases expression, increases abundance	4
bisphenol A	affects expression, increases expression	3
Acetaminophen	decreases expression	2
Benzo(a)pyrene	increases expression, decreases expression	2
Cisplatin	decreases expression, increases reaction	2
Doxorubicin	affects expression, decreases expression	2
Tobacco Smoke Pollution	decreases expression, affects expression	2
Valproic Acid	increases methylation, decreases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
arsenite	affects localization	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
quinoline	decreases expression	1
K 7174	decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	decreases expression	1
abrine	decreases expression	1
NSC 689534	affects binding, decreases expression	1
(+)-JQ1 compound	decreases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	decreases expression, increases abundance	1
Atrazine	increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118739	Binding	Binding affinity to ANP32A in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

3 cell lines: 1 embryonic stem cell, 1 transformed cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A1MX	WAe001-A-53	Embryonic stem cell	Male
CVCL_B2RN	Abcam HEK293T ANP32A KO	Transformed cell line	Female
CVCL_D7K3	Ubigene A-549 ANP32A KO	Cancer cell line	Male

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