ANP32B

Summary

ANP32B (acidic nuclear phosphoprotein 32 family member B, HGNC:16677) is a protein-coding gene on chromosome 9q22.33, encoding Acidic leucine-rich nuclear phosphoprotein 32 family member B (Q92688). Multifunctional protein that is involved in the regulation of many processes including cell proliferation, apoptosis, cell cycle progression or transcription.

Enables RNA polymerase binding activity and histone binding activity. Involved in several processes, including negative regulation of apoptotic process; nucleosome assembly; and positive regulation of protein export from nucleus. Located in cytoplasm; nucleolus; and nucleoplasm.

Source: NCBI Gene 10541 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 38 total — 4 pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_006401

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16677
Approved symbol	ANP32B
Name	acidic nuclear phosphoprotein 32 family member B
Location	9q22.33
Locus type	gene with protein product
Status	Approved
Aliases	SSP29, PHAPI2, APRIL
Ensembl gene	ENSG00000136938
Ensembl biotype	protein_coding
OMIM	619823
Entrez	10541

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 10 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000339399, ENST00000473205, ENST00000486769, ENST00000903803, ENST00000903804, ENST00000903805, ENST00000903806, ENST00000913152, ENST00000913153, ENST00000913154, ENST00000941386, ENST00000941387

RefSeq mRNA: 1 — MANE Select: NM_006401 NM_006401

CCDS: CCDS6732

Canonical transcript exons

ENST00000339399 — 7 exons

Exon	Start	End
ENSE00000983142	98004964	98005153
ENSE00001038075	98015364	98015943
ENSE00001038083	98011271	98011389
ENSE00001371353	97983341	97983609
ENSE00001383843	98012421	98012472
ENSE00003471343	97994631	97994780
ENSE00003622194	97998556	97998678

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.87.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 187.6186 / max 3612.0467, expressed in 1827 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
97590	171.0390	1827
97589	14.7700	1798
97592	1.4024	748
97591	0.4072	209

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	99.87	gold quality
trabecular bone tissue	UBERON:0002483	99.76	gold quality
cranial nerve II	UBERON:0000941	99.72	gold quality
cervix squamous epithelium	UBERON:0006922	99.69	gold quality
thymus	UBERON:0002370	99.62	gold quality
medial globus pallidus	UBERON:0002477	99.58	gold quality
corpus epididymis	UBERON:0004359	99.54	gold quality
cartilage tissue	UBERON:0002418	99.51	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	99.48	gold quality
parotid gland	UBERON:0001831	99.45	gold quality
caput epididymis	UBERON:0004358	99.45	gold quality
globus pallidus	UBERON:0001875	99.42	gold quality
inferior olivary complex	UBERON:0002127	99.41	gold quality
cauda epididymis	UBERON:0004360	99.41	gold quality
inferior vagus X ganglion	UBERON:0005363	99.37	gold quality
pylorus	UBERON:0001166	99.36	gold quality
hair follicle	UBERON:0002073	99.36	gold quality
amniotic fluid	UBERON:0000173	99.29	gold quality
endometrium epithelium	UBERON:0004811	99.27	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.26	gold quality
spinal cord	UBERON:0002240	99.25	gold quality
superficial temporal artery	UBERON:0001614	99.18	gold quality
middle frontal gyrus	UBERON:0002702	99.10	gold quality
mammalian vulva	UBERON:0000997	99.09	gold quality
embryo	UBERON:0000922	99.07	gold quality
medulla oblongata	UBERON:0001896	99.07	gold quality
oral cavity	UBERON:0000167	99.06	gold quality
mammary duct	UBERON:0001765	99.06	gold quality
epithelium of mammary gland	UBERON:0003244	99.03	gold quality
skin of hip	UBERON:0001554	99.02	gold quality

Single-cell (SCXA)

Detected in 16 experiment(s), a significant marker in 13.

Experiment	Marker?	Max mean expression
E-CURD-46	yes	1018.75
E-HCAD-4	yes	138.82
E-CURD-114	yes	63.20
E-CURD-122	yes	23.32
E-HCAD-1	yes	22.27
E-GEOD-125970	yes	22.08
E-HCAD-13	yes	21.69
E-HCAD-5	yes	19.55
E-MTAB-10553	yes	10.48
E-MTAB-10042	yes	9.48
E-MTAB-9388	yes	7.94
E-CURD-88	yes	6.71
E-MTAB-9221	no	783.36
E-HCAD-6	no	18.70
E-MTAB-8271	no	9.06

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): KLF5

miRNA regulators (miRDB)

82 targeting ANP32B, 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-4533	100.00	69.48	2758
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-548Y	99.94	71.28	3514
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488

Literature-anchored findings (GeneRIF, showing 20)

• regulatory roles of oncoprotein ProT and tumor suppressor PHAP in apoptosis (PMID:12522243)
• recruitment of ANP32B onto the promoter region requires KLF5 and results in promoter region-specific histone incorporation and inhibition of histone acetylation by ANP32B (PMID:18039846)
• The CK2 alpha’ phosphorylates APRIL and therefore is responsible for the regulation of the nucleocytoplasmic translocation of CD83 mRNA. (PMID:19130553)
• ANP32B is a direct substrate of caspase-3. It is cleaved at the sequence of Ala-Glu-Val-Asp, after Asp-163. The reduced expression of endogenous ANP32B by specific siRNA enhances caspase-3 activation & apoptosis induction by NSC606985 & etoposide. (PMID:20015864)
• the interaction of ANP32B with the core histones H3-H4 occurs on its concave side, and both the acidic and hydrophobic residues that compose the concave surface are critical for histone binding. (PMID:20538007)
• this is the first demonstration that ANP32B expression was down-regulated during differentiation induction of leukemic cells by all-trans retinoic acid. (PMID:22705300)
• ANP32B is a nuclear target of henipavirus M proteins. (PMID:24823948)
• Caspase-3-resistant uncleavable form of acidic leucine-rich nuclear phosphoprotein 32B potentiates leukemic cell apoptosis. (PMID:25483709)
• ANP32B modulates Bad phosphorylation as well as Bak and Bax expression, resulting in regulation of apoptosis in HCC. These findings indicate the potential value of ANP32B as a therapeutic target for HCC (PMID:28486557)
• 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)
• 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)
• ANP32A and ANP32B mediate the export of unspliced or partially spliced viral mRNA via interactions with Rev and CRM1. (PMID:31444273)
• Interaction of host cellular factor ANP32B with matrix proteins of different paramyxoviruses. (PMID:31793855)
• A natural variant in ANP32B impairs influenza virus replication in human cells. (PMID:34524075)
• KPNA6 is a Cofactor of ANP32A/B in Supporting Influenza Virus Polymerase Activity. (PMID:35044222)
• ANP32B promotes lung cancer progression by regulating VDAC1. (PMID:36642319)
• The histone chaperone ANP32B regulates chromatin incorporation of the atypical human histone variant macroH2A. (PMID:37858472)
• ANP32B inhibition suppresses the growth of prostate cancer cells by regulating c-Myc signaling. (PMID:38266312)
• Structures of H5N1 influenza polymerase with ANP32B reveal mechanisms of genome replication and host adaptation. (PMID:38750014)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	anp32b	ENSDARG00000023330
mus_musculus	Anp32b	ENSMUSG00000028333
rattus_norvegicus	Anp32b	ENSRNOG00000009266
drosophila_melanogaster	Mapmodulin	FBGN0034282
caenorhabditis_elegans	F33H2.3	WBGENE00009367
caenorhabditis_elegans		WBGENE00020588

Paralogs (3): ANP32D (ENSG00000139223), ANP32A (ENSG00000140350), ANP32E (ENSG00000143401)

Protein

Protein identifiers

Acidic leucine-rich nuclear phosphoprotein 32 family member B — Q92688 (reviewed: Q92688)

Alternative names: Acidic protein rich in leucines, Putative HLA-DR-associated protein I-2, Silver-stainable protein SSP29

All UniProt accessions (1): Q92688

UniProt curated annotations — full annotation on UniProt →

Function. Multifunctional protein that is involved in the regulation of many processes including cell proliferation, apoptosis, cell cycle progression or transcription. Regulates the proliferation of neuronal stem cells, differentiation of leukemic cells and progression from G1 to S phase of the cell cycle. As negative regulator of caspase-3-dependent apoptosis, may act as an antagonist of ANP32A in regulating tissue homeostasis. Exhibits histone chaperone properties, able to recruit histones to certain promoters, thus regulating the transcription of specific genes. Also plays an essential role in the nucleocytoplasmic transport of specific mRNAs via the uncommon nuclear mRNA export receptor XPO1/CRM1. Participates in the regulation of adequate adaptive immune responses by acting on mRNA expression and cell proliferation. (Microbial infection) Plays an essential role in influenza A and B viral genome replication. Also plays a role in foamy virus mRNA export from the nucleus to the cytoplasm.

Subunit / interactions. Interacts with histones H3 and H4. Interacts with KLF5; this interaction induces promoter region-specific histone incorporation and inhibition of histone acetylation by ANP32B. (Microbial infection) Interacts with Sendai virus protein M. (Microbial infection) Interacts with Measles virus protein M. (Microbial infection) Interacts with Hendra virus protein M; this interaction promotes nuclear localization of M. (Microbial infection) Interacts with influenza virus B protein PB2; this interaction strongly supports influenza B virus replication.

Subcellular location. Nucleus. Cytoplasm Cytoplasm.

Tissue specificity. Expressed in heart, lung, pancreas, prostate and in spleen, thymus and placenta.

Post-translational modifications. 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. Directly cleaved by caspase-3/CASP3.

Domain organisation. Histone binding is mediated by the concave surface of the LRR region.

Miscellaneous. No canonical donor splice site.

Similarity. Belongs to the ANP32 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q92688-1	1, Anp32b1, PHAPI2b	yes
Q92688-2	2, Anp32b2, PHAPI2b

RefSeq proteins (1): NP_006392* (*=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 (32 total): strand 9, helix 7, repeat 4, modified residue 3, compositionally biased region 2, chain 1, splice variant 1, mutagenesis site 1, sequence conflict 1, domain 1, region of interest 1, short sequence motif 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
8R1L	ELECTRON MICROSCOPY	3.1
8R1J	ELECTRON MICROSCOPY	3.2
2ELL	SOLUTION NMR
2RR6	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92688-F1	78.89	0.60

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 (3): 86, 158, 244

Mutagenesis-validated functional residues (1):

Position	Phenotype
163	complete loss of cleavage by casp3.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 255 (showing top): GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, PAL_PRMT5_TARGETS_UP, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT, MORF_UBE2I, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, MORF_HDAC1, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, MORF_RAD21, GOBP_REGULATION_OF_PROTEIN_EXPORT_FROM_NUCLEUS, HSIAO_HOUSEKEEPING_GENES, GNF2_MCM5, GOBP_VENTRICULAR_SYSTEM_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_TRANSPORT, GOBP_NUCLEAR_TRANSPORT, MORF_SKP1A

GO Biological Process (9): vasculature development (GO:0001944), nucleosome assembly (GO:0006334), ventricular system development (GO:0021591), regulation of apoptotic process (GO:0042981), negative regulation of apoptotic process (GO:0043066), negative regulation of cell differentiation (GO:0045596), positive regulation of protein export from nucleus (GO:0046827), inner ear development (GO:0048839), roof of mouth development (GO:0060021)

GO Molecular Function (3): histone binding (GO:0042393), RNA polymerase binding (GO:0070063), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), extracellular exosome (GO:0070062), nucleolus (GO:0005730)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
system development	2
apoptotic process	2
anatomical structure development	2
nuclear lumen	2
cellular anatomical structure	2
circulatory system development	1
chromatin organization	1
nucleosome organization	1
protein-DNA complex assembly	1
brain development	1
regulation of programmed cell death	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
cell differentiation	1
regulation of cell differentiation	1
negative regulation of cellular process	1
negative regulation of developmental process	1
protein export from nucleus	1
positive regulation of nucleocytoplasmic transport	1
regulation of protein export from nucleus	1
positive regulation of intracellular protein transport	1
ear development	1
protein binding	1
enzyme binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
extracellular vesicle	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

121 interactions, top by confidence:

A	B	Type	Score
KPNA1	ANP32B	psi-mi:“MI:0915”(physical association)	0.840
ANP32B	KPNA1	psi-mi:“MI:0915”(physical association)	0.840
KPNA1	ANP32B	psi-mi:“MI:0403”(colocalization)	0.840
KPNA6	RNMT	psi-mi:“MI:0914”(association)	0.800
KPNA5	ANP32B	psi-mi:“MI:0915”(physical association)	0.780
ANP32B	KPNA5	psi-mi:“MI:0915”(physical association)	0.780
SDCBP	ANP32B	psi-mi:“MI:0915”(physical association)	0.720
ANP32B	SDCBP	psi-mi:“MI:0915”(physical association)	0.720
KPNA6	ANP32B	psi-mi:“MI:0915”(physical association)	0.670
KPNA1	TCERG1	psi-mi:“MI:0914”(association)	0.640
MEOX2	ANP32B	psi-mi:“MI:0915”(physical association)	0.560
ANP32B		psi-mi:“MI:0915”(physical association)	0.560
BEND7	ANP32B	psi-mi:“MI:0915”(physical association)	0.560
ANP32B	MYNN	psi-mi:“MI:0915”(physical association)	0.560
	ANP32B	psi-mi:“MI:0915”(physical association)	0.560
ANP32B	DNTTIP1	psi-mi:“MI:0915”(physical association)	0.560
ANP32B	FAM217B	psi-mi:“MI:0915”(physical association)	0.560
YAF2	ANP32B	psi-mi:“MI:0915”(physical association)	0.560
ANP32B	HSPB1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (218): ANP32B (Affinity Capture-MS), ANP32B (Two-hybrid), ANP32B (Two-hybrid), ANP32B (Two-hybrid), ANP32B (Two-hybrid), ANP32B (Reconstituted Complex), AHCYL1 (Co-fractionation), AHCYL2 (Co-fractionation), ANP32B (Co-fractionation), ANP32B (Co-fractionation), ANP32B (Co-fractionation), DMAP1 (Co-fractionation), VPS72 (Co-fractionation), ANP32B (Affinity Capture-MS), KLF5 (Affinity Capture-Western)

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
CSNK2A1	up-regulates	ANP32B	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 100 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
Antimicrobial mechanism of IFN-stimulated genes	5	12.5×	7e-03
Regulation of PTEN stability and activity	5	11.7×	8e-03
Programmed Cell Death	6	11.1×	4e-03
Influenza Infection	5	11.1×	8e-03
Apoptosis	5	10.6×	9e-03
Activation of STAT3 by cadherin engagement	5	10.3×	9e-03
ISG15 antiviral mechanism	5	9.5×	1e-02
Signaling by ALK fusions and activated point mutants	5	9.5×	1e-02

GO biological processes:

GO term	Partners	Fold	FDR
NLS-bearing protein import into nucleus	5	47.8×	3e-05
cellular response to UV	5	17.6×	2e-03
protein import into nucleus	8	13.7×	5e-05
protein dephosphorylation	5	13.2×	5e-03
positive regulation of protein ubiquitination	5	12.7×	5e-03
glucose homeostasis	7	10.9×	9e-04
DNA damage response	9	5.7×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	23
Likely benign	2
Benign	3

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1341973	GRCh37/hg19 9q22.2-31.1(chr9:93864974-106661581)x1	Pathogenic
145977	GRCh38/hg38 9q22.32-22.33(chr9:94713892-98121186)x1	Pathogenic
59902	GRCh38/hg38 9q22.31-22.33(chr9:92561720-98122580)x3	Pathogenic
929316	GRCh37/hg19 9q22.31-31.2(chr9:96126075-108535272)x1	Pathogenic

SpliceAI

1942 predictions. Top by Δscore:

Variant	Effect	Δscore
9:97983607:GCT:G	donor_gain	1.0000
9:97983610:G:GG	donor_gain	1.0000
9:97994625:CCACA:C	acceptor_loss	1.0000
9:97994626:CACA:C	acceptor_loss	1.0000
9:97994629:A:AG	acceptor_gain	1.0000
9:97994629:A:C	acceptor_loss	1.0000
9:97994629:AG:A	acceptor_gain	1.0000
9:97994630:G:GG	acceptor_gain	1.0000
9:97994630:GG:G	acceptor_gain	1.0000
9:97994630:GGTTC:G	acceptor_gain	1.0000
9:97994777:AAAG:A	donor_gain	1.0000
9:97994778:AAG:A	donor_gain	1.0000
9:97994778:AAGG:A	donor_loss	1.0000
9:97994779:AG:A	donor_gain	1.0000
9:97994780:GG:G	donor_gain	1.0000
9:97994780:GGTA:G	donor_loss	1.0000
9:97994781:G:GG	donor_gain	1.0000
9:97998543:T:G	acceptor_gain	1.0000
9:97998553:CA:C	acceptor_loss	1.0000
9:97998554:A:AG	acceptor_gain	1.0000
9:97998554:A:T	acceptor_loss	1.0000
9:97998554:AGCTT:A	acceptor_gain	1.0000
9:97998555:G:GC	acceptor_gain	1.0000
9:97998555:GC:G	acceptor_gain	1.0000
9:97998555:GCT:G	acceptor_gain	1.0000
9:97998555:GCTT:G	acceptor_gain	1.0000
9:97998555:GCTTG:G	acceptor_gain	1.0000
9:97998674:CTTTG:C	donor_gain	1.0000
9:97998675:TTTG:T	donor_gain	1.0000
9:97998676:TTG:T	donor_gain	1.0000

AlphaMissense

1691 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:97994641:T:C	L22P	1.000
9:97994650:A:T	D25V	1.000
9:97994716:T:C	L47P	1.000
9:97994773:T:G	L66W	1.000
9:97998557:T:C	L69P	1.000
9:97998573:T:A	N74K	1.000
9:97998573:T:G	N74K	1.000
9:97998620:T:A	L90H	1.000
9:97998629:T:A	L93Q	1.000
9:97998629:T:C	L93P	1.000
9:97998635:T:C	L95S	1.000
9:97998645:T:A	N98K	1.000
9:97998645:T:G	N98K	1.000
9:98004989:T:A	L118Q	1.000
9:98004989:T:C	L118P	1.000
9:98004995:T:C	L120P	1.000
9:98004997:T:C	F121L	1.000
9:98004999:T:A	F121L	1.000
9:98004999:T:G	F121L	1.000
9:98005027:T:C	Y131H	1.000
9:98005070:T:C	L145S	1.000
9:98005073:A:T	D146V	1.000
9:97983572:G:T	R6M	0.999
9:97983581:T:C	L9P	0.999
9:97983583:G:A	E10K	0.999
9:97983587:T:C	L11P	0.999
9:97983590:G:T	R12M	0.999
9:97994647:T:C	L24S	0.999
9:97994647:T:G	L24W	0.999
9:97994649:G:C	D25H	0.999

dbSNP variants (sampled 300 via entrez): RS1000014447 (9:98011332 A>C,T), RS1000022416 (9:97994801 A>G), RS1000054772 (9:97994384 T>G), RS1000062274 (9:97986096 C>T), RS1000078875 (9:97983191 C>T), RS1000092744 (9:97988530 G>C), RS1000113159 (9:97991537 C>G,T), RS1000249397 (9:97991881 C>G), RS1000280248 (9:98007313 T>A), RS1000417303 (9:98007530 T>C), RS1000477007 (9:97997272 GA>G,GAA), RS1000539428 (9:97986320 T>G), RS1000548097 (9:98010133 C>T), RS1000622702 (9:98005768 C>T), RS1000650115 (9:98004041 TA>T)

Disease associations

OMIM: gene MIM:619823 | disease phenotypes: MIM:109400, MIM:607906, MIM:616228, MIM:607086

GenCC curated gene-disease

Mondo (4): nevoid basal cell carcinoma syndrome (MONDO:0007187), ALG2-congenital disorder of glycosylation (MONDO:0011933), congenital myasthenic syndrome 14 (MONDO:0014543), familial thoracic aortic aneurysm and aortic dissection (MONDO:0019625)

Orphanet (5): Gorlin syndrome (Orphanet:377), Congenital myasthenic syndrome with glycosylation defect (Orphanet:353327), Congenital myasthenic syndrome (Orphanet:590), ALG2-CDG (Orphanet:79326), Familial thoracic aortic aneurysm and aortic dissection (Orphanet:91387)

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST002707_12	Serum thyroid-stimulating hormone levels	6.000000e-06
GCST004601_117	Red blood cell count	9.000000e-11
GCST004628_104	Immature fraction of reticulocytes	1.000000e-11
GCST004630_230	Mean corpuscular hemoglobin	8.000000e-14
GCST004866_3	Alopecia areata	9.000000e-07
GCST005196_170	Coronary artery disease	4.000000e-06
GCST90002381_478	Eosinophil count	7.000000e-12
GCST90002390_393	Mean corpuscular hemoglobin	3.000000e-35
GCST90002392_541	Mean corpuscular volume	2.000000e-51
GCST90002403_612	Red blood cell count	5.000000e-28

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004305	erythrocyte count
EFO:0007986	reticulocyte count
EFO:0004527	mean corpuscular hemoglobin
EFO:0004842	eosinophil count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D001478	Basal Cell Nevus Syndrome	C04.182.089.530.690.150; C04.557.470.200.165.150; C04.557.470.565.165.150; C04.700.175; C05.116.099.105; C05.500.470.690.150; C07.320.450.670.130; C16.131.077.130; C16.320.700.175

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295917 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
6.09	IC50	810	nM	MOLIBRESIB
5.29	Kd	5151	nM	CHEMBL3752910
5.29	ED50	5151	nM	CHEMBL3752910
5.00	Kd	1.008e+04	nM	CHEMBL5653589
5.00	ED50	1.008e+04	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 12 total; 2 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
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178877: Inhibition of ANP32B (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.8100	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147852: Binding affinity to human ANP32B incubated for 45 mins by Kinobead based pull down assay	kd	5.1511	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases methylation	5
bisphenol A	affects expression, increases expression	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine	decreases expression	1
propionaldehyde	decreases expression	1
trichostatin A	affects expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
fludarabine	affects cotreatment, increases cleavage	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
Arsenic Trioxide	increases expression	1
Vorinostat	decreases expression	1
Clofarabine	affects cotreatment, increases cleavage	1
Air Pollutants	decreases expression, increases abundance	1
Aminoglutethimide	decreases expression	1
Benzo(a)pyrene	increases expression	1
Busulfan	affects cotreatment, increases cleavage	1
Cannabidiol	increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Diethylstilbestrol	increases expression	1
Diuron	decreases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1

ChEMBL screening assays

9 unique, capped per target: 9 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118720	Binding	Binding affinity to ANP32B 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

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2RP	Abcam HEK293T ANP32B KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00049959	PHASE3	TERMINATED	Two Studies to Determine if Verteporfin PDT is Effective & Safe in Treating Multiple Basal Cell Carcinoma of the Skin.
NCT03703310	PHASE3	COMPLETED	Study of Patidegib Topical Gel, 2%, for the Reduction of Disease Burden of Persistently Developing Basal Cell Carcinomas (BCCs) in Subjects With Basal Cell Nevus Syndrome (Gorlin Syndrome)
NCT04308395	PHASE3	TERMINATED	Extension Study of Patidegib Topical Gel, 2% in Subjects With Gorlin Syndrome (Basal Cell Nevus Syndrome)
NCT06050122	PHASE3	ACTIVE_NOT_RECRUITING	Efficacy and Safety of Patidegib Gel 2% for Preventing Basal Cell Carcinomas on the Face of Adults With Gorlin Syndrome
NCT00957229	PHASE2	COMPLETED	To Determine The Efficacy and Safety of GDC-0449 in Patients With Basal Cell Nevus Syndrome (BCNS)
NCT01350115	PHASE2	COMPLETED	Efficacy, Safety and Pharmacokinetics of Oral LDE225 in Treatment of Patients With Nevoid Basal Cell Carcinoma Syndrome (NBCCS)
NCT01556009	PHASE2	COMPLETED	Trial Comparing the Effects of Intermittent Vismodegib vs. PDT in Patients With Multiple Basal Cell Carcinomas
NCT02017964	PHASE2	COMPLETED	Combination Chemotherapy in Treating Younger Patients With Newly Diagnosed, Non-metastatic Desmoplastic Medulloblastoma
NCT02303041	PHASE2	TERMINATED	Pilot Study of Sonidegib and Buparlisib in Treating Patients With Advanced or Metastatic Basal Cell Carcinoma
NCT02762084	PHASE2	COMPLETED	Trial of Patidegib Gel 2%, 4%, and Vehicle to Decrease the Number of Surgically Eligible Basal Cell Carcinomas in Gorlin Syndrome Patients
NCT03767439	PHASE2	WITHDRAWN	Nivolumab With Vismodegib in Patients With Basal Cell Nevus Syndrome
NCT04416516	PHASE2	COMPLETED	Safety and Efficacy of ASN-002 Combined With a Hedgehog Pathway Inhibitor
NCT03467789	PHASE1	COMPLETED	Vitamin D as a Nutritional Neoadjuvant During Photodynamic Therapy of Basal Cell Carcinoma
NCT02550678	PHASE1/PHASE2	COMPLETED	A Study of the Efficacy and Safety of ASN-002 in Adult Patients With Low-risk Nodular Basal Cell Carcinoma
NCT00555633	Not specified	COMPLETED	Use of an SPF30 Sunscreen and an After-sun-lotion in Skin Cancer Risk Patients
NCT02100371	Not specified	COMPLETED	Study of BMS-833923 in Two Specific Patients With Basal Cell Nevus Syndrome
NCT02157623	Not specified	COMPLETED	Blue vs Red Light During Levulan Based Photodynamic Therapy in Patients With Basal Cell Nevus Syndrome
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT05463757	Not specified	RECRUITING	Oral Hedgehog Inhibitors in the Treatment of Basal Cell Carcinoma in the Netherlands: a Prospective Registration Study
NCT05898347	Not specified	UNKNOWN	Nevoid Basal Cell Carcinomas in Gorlin Syndrome
NCT06330324	Not specified	ENROLLING_BY_INVITATION	Reproductive Options in Inherited Skin Diseases
NCT06330350	Not specified	RECRUITING	Qualitative Study in Patients With Genodermatoses and Healthcare Professionals on Reproductive Counselling
NCT03440697	Not specified	ACTIVE_NOT_RECRUITING	Pathogenetic Basis of Aortopathy and Aortic Valve Disease
NCT06783803	Not specified	ACTIVE_NOT_RECRUITING	Application of Linkage Analysis in the Identification of Novel Hereditary Factors in Familial Aneurysms