APOBEC3B

Summary

APOBEC3B (apolipoprotein B mRNA editing enzyme catalytic subunit 3B, HGNC:17352) is a protein-coding gene on chromosome 22q13.1, encoding DNA dC->dU-editing enzyme APOBEC-3B (Q9UH17). DNA deaminase (cytidine deaminase) which acts as an inhibitor of retrovirus replication and retrotransposon mobility via deaminase-dependent and -independent mechanisms.

This gene is a member of the cytidine deaminase gene family. It is one of seven related genes or pseudogenes found in a cluster, thought to result from gene duplication, on chromosome 22. Members of the cluster encode proteins that are structurally and functionally related to the C to U RNA-editing cytidine deaminase APOBEC1. It is thought that the proteins may be RNA editing enzymes and have roles in growth or cell cycle control. A hybrid gene results from the deletion of approximately 29.5 kb of sequence between this gene, APOBEC3B, and the adjacent gene APOBEC3A. The breakpoints of the deletion are within the two genes, so the deletion allele is predicted to have the promoter and coding region of APOBEC3A, but the 3’ UTR of APOBEC3B. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 9582 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 53 total
• Druggable target: yes
• MANE Select transcript: NM_004900

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17352
Approved symbol	APOBEC3B
Name	apolipoprotein B mRNA editing enzyme catalytic subunit 3B
Location	22q13.1
Locus type	gene with protein product
Status	Approved
Aliases	PHRBNL, FLJ21201
Ensembl gene	ENSG00000179750
Ensembl biotype	protein_coding
OMIM	607110
Entrez	9582

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 nonsense_mediated_decay

ENST00000333467, ENST00000335760, ENST00000402182, ENST00000407298

RefSeq mRNA: 2 — MANE Select: NM_004900 NM_001270411, NM_004900

CCDS: CCDS13982, CCDS58807

Canonical transcript exons

ENST00000333467 — 8 exons

Exon	Start	End
ENSE00001389632	38984075	38984231
ENSE00001593845	38985812	38986091
ENSE00001727558	38989457	38989610
ENSE00001729638	38986298	38986412
ENSE00001930304	38992431	38992779
ENSE00001956540	38982347	38982470
ENSE00003490112	38991332	38991626
ENSE00003605351	38992034	38992149

Expression profiles

Bgee: expression breadth ubiquitous, 124 present calls, max score 96.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.9434 / max 158.0061, expressed in 1139 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
192292	4.8789	1059
192291	1.0646	517

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	96.16	gold quality
mucosa of transverse colon	UBERON:0004991	88.01	gold quality
bone marrow	UBERON:0002371	84.14	gold quality
rectum	UBERON:0001052	81.73	gold quality
blood	UBERON:0000178	81.70	gold quality
bone marrow cell	CL:0002092	80.94	gold quality
islet of Langerhans	UBERON:0000006	78.60	gold quality
stromal cell of endometrium	CL:0002255	78.31	gold quality
duodenum	UBERON:0002114	77.25	gold quality
vermiform appendix	UBERON:0001154	76.57	gold quality
lymph node	UBERON:0000029	74.59	gold quality
spleen	UBERON:0002106	72.78	gold quality
leukocyte	CL:0000738	72.60	gold quality
monocyte	CL:0000576	72.39	gold quality
transverse colon	UBERON:0001157	71.18	gold quality
placenta	UBERON:0001987	70.55	gold quality
granulocyte	CL:0000094	70.47	gold quality
pancreas	UBERON:0001264	69.97	gold quality
lower esophagus mucosa	UBERON:0035834	69.25	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	68.66	gold quality
smooth muscle tissue	UBERON:0001135	67.25	gold quality
endometrium	UBERON:0001295	66.97	gold quality
esophagus mucosa	UBERON:0002469	66.39	gold quality
body of pancreas	UBERON:0001150	65.92	gold quality
metanephros cortex	UBERON:0010533	65.66	gold quality
tonsil	UBERON:0002372	65.12	gold quality
minor salivary gland	UBERON:0001830	64.83	gold quality
saliva-secreting gland	UBERON:0001044	64.67	gold quality
right adrenal gland cortex	UBERON:0035827	63.58	gold quality
right adrenal gland	UBERON:0001233	63.39	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.19

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting APOBEC3B, 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-4307	99.82	70.45	3374
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-6833-5P	99.50	68.93	1161
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-3614-5P	99.30	65.25	837
HSA-MIR-29A-5P	99.08	68.59	1813
HSA-MIR-1207-3P	98.99	66.22	1532
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-34B-3P	98.70	67.40	1171
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-138-5P	98.43	70.49	1292
HSA-MIR-5581-5P	97.91	66.50	965
HSA-MIR-204-3P	97.80	66.84	1656
HSA-MIR-4646-5P	97.70	66.84	1692
HSA-MIR-4314	97.50	67.30	1369
HSA-MIR-890	97.47	68.67	982
HSA-MIR-4714-5P	97.04	67.76	955
HSA-MIR-505-5P	97.01	65.54	778
HSA-MIR-4522	95.76	66.23	742
HSA-MIR-4772-5P	95.60	68.04	617
HSA-MIR-550B-3P	95.43	67.73	599

Literature-anchored findings (GeneRIF, showing 40)

• different APOBEC3 family members function to neutralize specific lentiviruses (PMID:15466872)
• APOBEC3B reduces retrotransposition by the intracisternal A-particle. (PMID:16407327)
• APOBEC3B and APOBEC3F have roles in inhibiting L1 retrotransposition by a DNA deamination-independent mechanism (PMID:16648136)
• separation of function of the cytidine deaminase domains is maintained in hA3B and hA3F, but roles of the two domains are reversed in mouse A3 (PMID:17020885)
• detailed sequence and population genetic analysis of a 29.5-kb common human deletion polymorphism that removes the APOBEC3B gene. (PMID:17447845)
• HIV-1 Vif(IIIB) induces the emigration from the nucleus to the cytosol and thereby causes net increases in the cytosolic concentrations and anti-HIV-1 activities of APOBEC3A and APOBEC3B. (PMID:17977970)
• only the carboxy-terminal deaminase domain of APOBEC3B catalyses cytidine deaminations leading to hepatitis B virus (HBV) hypermutations;induction of hypermutations is not sufficient for full inhibition of HBV replication; both domains of must be intact (PMID:18024895)
• study provides evidence of editing of human papillomavirus 1a and 16 DNA by APOBEC3 in plantar warts and precancerous cervix biopsies (PMID:18403710)
• These findings suggest that the loss of APOBEC3B may increase host susceptibility to HIV-1 acquisition and progression to AIDS and warrant further study. (PMID:19698078)
• Studies indicate the APOBEC family consists of 11 members: APOBEC-1 (Apo1), APOBEC-2 (Apo2), activation induced cytidine deaminase (AID), APOBEC- 3A, -3B, -3C, -3DE, -3F, -3H (Apo3A-H) and APOBEC- 4 (Apo4). (PMID:19911124)
• Higher expression levels of hA3G and hA3B mRNA in the peripheral blood mononuclear cells of Chinese HIV-infected individuals were found to be associated with slower HIV disease progression. (PMID:20104108)
• These observations suggest that changing 4 residues in the amino terminus of A3B not only retargets the protein from the nucleus to the cytoplasm but also enhances its ability to restrict HIV while retaining inhibition of retrotransposition. (PMID:21715505)
• A3B appears to restrict engineered L1 retrotransposition in a broad range of cell types, including pluripotent cells. (PMID:21878639)
• Carriers of homozygous deletions in this gene show a significantly higher score in the alcohol dependence severity and increased response to alcohol cues (PMID:21995620)
• APOBEC3 deletion frequency differs vastly in Indian populations. The APOBEC3B insertion allele is strongly associated with protection from malaria. (PMID:22108670)
• The data suggested that the present-day human APOBEC3B enzyme retained the nuclear import mechanism of an ancestral activation-induced cytosine deaminase during the expansion of the APOBEC3 locus in primates. (PMID:22446380)
• The authors show that APOBEC3A, APOBEC3B, and APOBEC3H haplotype 2 (A3H hapII) acted as potent inhibitors of HTLV-1. (PMID:22457529)
• Both A3A and A3B of APOBEC3B can induce C/G to T/G transitions into genomic DNA without suppressing DNA repair system. (PMID:23150777)
• APOBEC3B gene deletion is associated with susceptibility to persistent HBV infection and hepatocellular carcinoma. (PMID:23213177)
• data suggest a model in which APOBEC3B-catalysed deamination provides a chronic source of DNA damage in breast cancers that could select TP53 inactivation and explain how some tumours evolve rapidly and manifest heterogeneity (PMID:23389445)
• Human APOBEC3B D316 is catalytically active and capable of restricting HIV-1 while rhesus APOBEC3B N316 is not; swapping these residues alters the activity and restriction phenotypes respectively. (PMID:23542011)
• Studies indicate that APOBEC3B (A3B) was identified as the mutational source in breast cancer cells, and APOBEC3G (A3G) was predominantly expressed in lymphoma cells and involved in DNA repair. (PMID:23598277)
• results implicate APOBEC3B/A in breast cancer hypermutation and give insight into the mechanism of kataegis (PMID:23599896)
• APOBEC3B-catalyzed genomic uracil lesions are responsible for a large proportion of both dispersed and clustered mutations in multiple distinct cancers. (PMID:23852168)
• This result suggests that genetic variations in APOBEC3 cytidine deaminases do not predispose to chronicity but may modulate the course of persistent hepatitis B virus infection. (PMID:24010642)
• Data identify a potential role for APOBEC3B in serous ovarian cancer genomic instability. (PMID:24154874)
• APOBEC3 deaminases upregulated by IFN-beta induce E2 hypermutation of HPV16 in cervical keratinocytes. (PMID:24227842)
• analysis of a population-based matched cohort suggests that the antiviral mechanism of APOBEC3B plays only a negligible role in eliminating HIV-1 in vivo. (PMID:24667791)
• The APOBEC3A-APOBEC3B germline deletion allele confers cancer susceptibility through increased activity of APOBEC-dependent mutational processes. (PMID:24728294)
• active involvement of HPV in the early stage of BC carcinogenesis via A3B induction (PMID:24858917)
• Findings implicate APOBEC3B activity as a key driver of PIK3CA mutagenesis and HPV-induced transformation. (PMID:24910434)
• marker of pure prognosis and poor outcomes for estrogen-receptor-positive breast cancer (PMID:25123150)
• Study provides evidence that APOBEC3B is overexpressed in chondrosarcoma tissues and cell lines and interferes with RUNX3 transcription. (PMID:25176183)
• The degradation efficiency of Vif correlated with both the binding strength of the APOBEC3-Vif interaction and the APOBEC3-Vif interface. (PMID:25275135)
• Germline A3B can hypermutate nuclear DNA, albeit less efficiently than A3A. Chimaeric A3A mRNA resulting from DeltaA3B was more stable, resulting in higher intracellular A3A levels and greater DNA damage. (PMID:25298230)
• APOBEC3B overexpression and Fhit-loss induced DNA damage are independent events that, when occurring together, result in a significantly increased frequency of APOBEC-induced mutations that drive cancer progression. (PMID:25401976)
• These studies suggest a model in which high-risk human papillomavirus E6 causes derepression of APOBEC3B gene transcription, leading to a mutator phenotype that explains the observed cytosine mutation biases in papillomavirus positive cancers. (PMID:25538195)
• High APOBEC3B is associated with the pathogenesis of primary effusion lymphoma. (PMID:25650088)
• breast cancers arising in homozygous A3B(del) individuals with A3B absent did not differ in these features, indicating that A3B expression is a reflection rather than a direct cause of increased proliferation. (PMID:25730878)
• APOBEC3B is a potential factor contributing to suppression of tumor growth in human hepatocellular carcinoma. (PMID:25750306)

Cross-species orthologs

0 orthologs

Paralogs (9): APOBEC3H (ENSG00000100298), APOBEC1 (ENSG00000111701), AICDA (ENSG00000111732), APOBEC2 (ENSG00000124701), APOBEC3A (ENSG00000128383), APOBEC3F (ENSG00000128394), APOBEC3G (ENSG00000239713), APOBEC3D (ENSG00000243811), APOBEC3C (ENSG00000244509)

Protein

Protein identifiers

DNA dC->dU-editing enzyme APOBEC-3B — Q9UH17 (reviewed: Q9UH17)

Alternative names: Phorbolin-1-related protein, Phorbolin-2/3

All UniProt accessions (2): Q9UH17, B0QYD3

UniProt curated annotations — full annotation on UniProt →

Function. DNA deaminase (cytidine deaminase) which acts as an inhibitor of retrovirus replication and retrotransposon mobility via deaminase-dependent and -independent mechanisms. After the penetration of retroviral nucleocapsids into target cells of infection and the initiation of reverse transcription, it can induce the conversion of cytosine to uracil in the minus-sense single-strand viral DNA, leading to G-to-A hypermutations in the subsequent plus-strand viral DNA. The resultant detrimental levels of mutations in the proviral genome, along with a deamination-independent mechanism that works prior to the proviral integration, together exert efficient antiretroviral effects in infected target cells. Selectively targets single-stranded DNA and does not deaminate double-stranded DNA or single- or double-stranded RNA. Exhibits antiviral activity against simian immunodeficiency virus (SIV), hepatitis B virus (HBV) and human T-cell leukemia virus type 1 (HTLV-1) and may inhibit the mobility of LTR and non-LTR retrotransposons.

Subunit / interactions. Homodimer. Interacts with APOBEC3G. Does not interact with APOBEC1.

Subcellular location. Nucleus.

Tissue specificity. Expressed at high and moderate levels in peripheral blood leukocytes, spleen, testes, heart, thymus, prostate and ovary. Also expressed at low levels in several other tissues.

Domain organisation. The CMP/dCMP deaminase domain 1 mediates RNA binding, RNA-dependent oligomerization and virion incorporation whereas the CMP/dCMP deaminase domain 2 confers deoxycytidine deaminase activity and substrate sequence specificity.

Induction. Phorbol 12-myristate 13-acetate (PMA) induces overexpression in keratinocytes. Up-regulated by IFN-alpha.

Miscellaneous. It is one of seven related genes or pseudogenes found in a cluster, thought to result from gene duplication, on chromosome 22. May be due to a competing donor splice site.

Similarity. Belongs to the cytidine and deoxycytidylate deaminase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9UH17-1	1	yes
Q9UH17-2	2
Q9UH17-3	3

RefSeq proteins (2): NP_001257340, NP_004891* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002125	CMP_dCMP_dom	Domain
IPR016192	APOBEC/CMP_deaminase_Zn-bd	Binding_site
IPR016193	Cytidine_deaminase-like	Homologous_superfamily
IPR050610	APOBEC_Cyt_Deaminase	Family

Pfam: PF18782

Enzyme classification (BRENDA):

• EC 3.5.4.38 — single-stranded DNA cytosine deaminase (BRENDA: 8 organisms, 58 substrates, 4 inhibitors, 11 Km, 10 kcat entries)

Substrate kinetics (BRENDA)

2 substrates with measured Km, best-characterized 2. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
CCCA	0.001–0.073	5
TTCA	0.001–0.019	5

Catalyzed reactions (Rhea), 1 shown:

• a 2’-deoxycytidine in single-stranded DNA + H2O + H(+) = a 2’-deoxyuridine in single-stranded DNA + NH4(+) (RHEA:50948)

UniProt features (53 total): helix 18, strand 12, binding site 6, sequence variant 5, sequence conflict 5, domain 2, splice variant 2, chain 1, active site 1, turn 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
5CQI	X-RAY DIFFRACTION	1.68
5TD5	X-RAY DIFFRACTION	1.72
5CQH	X-RAY DIFFRACTION	1.73
6NFL	X-RAY DIFFRACTION	1.73
5SXH	X-RAY DIFFRACTION	1.78
6NFK	X-RAY DIFFRACTION	1.86
5CQK	X-RAY DIFFRACTION	1.88
5TKM	X-RAY DIFFRACTION	1.9
5SXG	X-RAY DIFFRACTION	1.93
5CQD	X-RAY DIFFRACTION	2.08
6NFM	X-RAY DIFFRACTION	2.53
7RW6	ELECTRON MICROSCOPY	2.55
2NBQ	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UH17-F1	87.94	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.

Catalytic / active sites (1): 255 (proton donor)

Ligand- & substrate-binding residues (6): 66; 97; 100; 253; 284; 289

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-72200	mRNA Editing: C to U Conversion
R-HSA-75094	Formation of the Editosome
R-HSA-75072	mRNA Editing
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 252 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, HORIUCHI_WTAP_TARGETS_DN, CROONQUIST_NRAS_SIGNALING_DN, GOBP_NEGATIVE_REGULATION_OF_VIRAL_PROCESS, SHAFFER_IRF4_TARGETS_IN_PLASMA_CELL_VS_MATURE_B_LYMPHOCYTE, BENNETT_SYSTEMIC_LUPUS_ERYTHEMATOSUS, GOBP_DNA_MODIFICATION, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_RNA_MODIFICATION, CHEOK_RESPONSE_TO_MERCAPTOPURINE_DN, DOANE_RESPONSE_TO_ANDROGEN_DN, LI_WILMS_TUMOR_VS_FETAL_KIDNEY_1_DN, BROWNE_HCMV_INFECTION_14HR_DN, GOBP_VIRAL_GENOME_REPLICATION, GOBP_VIRAL_LIFE_CYCLE

GO Biological Process (9): transposable element silencing (GO:0010526), cytidine to uridine editing (GO:0016554), clearance of foreign intracellular DNA (GO:0044355), innate immune response (GO:0045087), negative regulation of single stranded viral RNA replication via double stranded DNA intermediate (GO:0045869), defense response to virus (GO:0051607), DNA cytosine deamination (GO:0070383), immune system process (GO:0002376), negative regulation of macromolecule biosynthetic process (GO:0010558)

GO Molecular Function (7): RNA binding (GO:0003723), cytidine deaminase activity (GO:0004126), zinc ion binding (GO:0008270), catalytic activity (GO:0003824), protein binding (GO:0005515), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (4): P-body (GO:0000932), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
mRNA Editing	1
mRNA Editing: C to U Conversion	1
Metabolism of RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
negative regulation of gene expression	1
retrotransposition	1
base conversion or substitution editing	1
clearance of foreign intracellular nucleic acids	1
immune response	1
defense response to symbiont	1
single stranded viral RNA replication via double stranded DNA intermediate	1
negative regulation of viral genome replication	1
regulation of single stranded viral RNA replication via double stranded DNA intermediate	1
negative regulation of RNA biosynthetic process	1
defense response	1
response to virus	1
DNA deamination	1
biological_process	1
macromolecule biosynthetic process	1
negative regulation of biosynthetic process	1
regulation of macromolecule biosynthetic process	1
negative regulation of macromolecule metabolic process	1
nucleic acid binding	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amidines	1
deaminase activity	1
transition metal ion binding	1
molecular_function	1
binding	1
catalytic activity	1
cation binding	1
cytoplasmic ribonucleoprotein granule	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1266 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
APOBEC3B	CDA	P32320	883
APOBEC3B	APOB	P04114	758
APOBEC3B	CUL5	Q93034	754
APOBEC3B	APOBEC4	Q8WW27	746
APOBEC3B	UNG	P13051	635
APOBEC3B	APOBEC3H	Q6NTF7	520
APOBEC3B	NF1	P21359	486
APOBEC3B	TRIM5	Q9C035	471
APOBEC3B	HNRNPUL1	Q9BUJ2	458
APOBEC3B	PIWIL2	Q8TC59	450
APOBEC3B	TP53	P04637	431
APOBEC3B	REV1	Q9UBZ9	425
APOBEC3B	APOBEC3C	Q9NRW3	414
APOBEC3B	RBX1	P62877	412
APOBEC3B	APOBEC3F	Q8IUX4	410

IntAct

63 interactions, top by confidence:

A	B	Type	Score
APOBEC3B	CDK4	psi-mi:“MI:0915”(physical association)	0.640
CDK4	APOBEC3B	psi-mi:“MI:0915”(physical association)	0.640
APOBEC3B	CDK4	psi-mi:“MI:0407”(direct interaction)	0.640
APOBEC3B	CDK4	psi-mi:“MI:2364”(proximity)	0.640
APOBEC3B	CDK4	psi-mi:“MI:0403”(colocalization)	0.640
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
HNRNPH2	PLOD2	psi-mi:“MI:0914”(association)	0.530
N	RBM47	psi-mi:“MI:0914”(association)	0.530
ELAVL2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
ILF2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
GSPT2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
RPS2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
APOBEC3B	ORF40	psi-mi:“MI:0915”(physical association)	0.400
Dctn3		psi-mi:“MI:0914”(association)	0.350
Snrnp70	GEMIN2	psi-mi:“MI:0914”(association)	0.350
Taf15	BTBD10	psi-mi:“MI:0914”(association)	0.350
Shcbp1	DERL1	psi-mi:“MI:0914”(association)	0.350
MATR3	BCLAF3	psi-mi:“MI:0914”(association)	0.350
HNRNPA1	MATR3	psi-mi:“MI:0914”(association)	0.350
BCLAF1	PABPN1	psi-mi:“MI:0914”(association)	0.350
Fus	DDX3X	psi-mi:“MI:0914”(association)	0.350
PPP1CC	CLIC1	psi-mi:“MI:0914”(association)	0.350
PPP1CB	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Srsf1	SRRM1	psi-mi:“MI:0914”(association)	0.350
MKI67	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (150): APOBEC3B (Affinity Capture-MS), APOBEC3B (Affinity Capture-MS), APOBEC3B (Affinity Capture-MS), APOBEC3B (Affinity Capture-MS), APOBEC3B (Affinity Capture-MS), APOBEC3B (Affinity Capture-MS), APOBEC3B (Affinity Capture-MS), APOBEC3B (Affinity Capture-MS), APOBEC3B (Affinity Capture-MS), APOBEC3B (Affinity Capture-MS), APOBEC3B (Affinity Capture-MS), APOBEC3B (Affinity Capture-MS), APOBEC3B (Affinity Capture-MS), APOBEC3B (Affinity Capture-MS), APOBEC3B (Affinity Capture-MS)

ESM2 similar proteins: A2VDP6, A9QA56, G1SRW8, P0C7P3, P31941, P60704, P60705, Q08AF3, Q19Q52, Q1WBT4, Q2PT36, Q3SYR3, Q4VDN5, Q5RCA5, Q5XI89, Q68D06, Q694B4, Q694B5, Q694B6, Q694B7, Q694B8, Q694B9, Q694C0, Q694C1, Q694C2, Q694C4, Q694C5, Q6NTF7, Q75W64, Q7YR23, Q7YR24, Q7YR25, Q7Z7L1, Q8IUX4, Q8IXQ6, Q969Y0, Q96AK3, Q99J72, Q9BQQ7, Q9GZX7

Diamond homologs: A9QA56, P31941, P38483, P41238, P47855, P60704, P60705, Q19Q52, Q1WBT4, Q2PT36, Q4VDN5, Q694B3, Q694B5, Q694B6, Q694B7, Q694B8, Q694B9, Q694C0, Q694C1, Q694C2, Q694C4, Q694C5, Q6NTF7, Q75W64, Q7YR23, Q7YR24, Q7YR25, Q8IUX4, Q99J72, Q9EQP0, Q9GZX7, Q9HC16, Q9NRW3, Q9TUI7, Q9UH17, Q9WVE0, Q3SYR3, Q694B4, Q96AK3, Q9WV35

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
APOBEC3B	up-regulates	“Clearance_of_foreign intracellular_DNA”
PRKACA	“down-regulates activity”	APOBEC3B	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 65 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
Macroautophagy	5	16.5×	5e-04
mRNA Splicing	5	15.7×	5e-04
mRNA Polyadenylation	6	15.1×	2e-04
Processing of Capped Intron-Containing Pre-mRNA	6	14.1×	2e-04
Metabolism of RNA	8	9.5×	2e-04
mRNA Splicing - Major Pathway	6	9.4×	8e-04
Dengue Virus-Host Interactions	7	9.1×	5e-04

GO biological processes:

GO term	Partners	Fold	FDR
mitophagy	5	31.8×	7e-05
autophagosome assembly	5	22.5×	2e-04
RNA splicing	6	10.6×	1e-03
mRNA processing	6	9.4×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	8
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1099 predictions. Top by Δscore:

Variant	Effect	Δscore
22:38984169:G:GT	donor_gain	1.0000
22:38989659:G:T	donor_gain	1.0000
22:38991329:TA:T	acceptor_loss	1.0000
22:38991330:A:AG	acceptor_gain	1.0000
22:38991330:A:G	acceptor_loss	1.0000
22:38991330:AG:A	acceptor_gain	1.0000
22:38991331:G:GT	acceptor_gain	1.0000
22:38991331:GG:G	acceptor_gain	1.0000
22:38991331:GGC:G	acceptor_gain	1.0000
22:38991331:GGCTA:G	acceptor_gain	1.0000
22:38991622:CGATG:C	donor_gain	1.0000
22:38991623:GATG:G	donor_gain	1.0000
22:38991623:GATGG:G	donor_gain	1.0000
22:38991624:ATG:A	donor_gain	1.0000
22:38991624:ATGG:A	donor_loss	1.0000
22:38991625:TG:T	donor_gain	1.0000
22:38991626:GG:G	donor_gain	1.0000
22:38991627:G:GG	donor_gain	1.0000
22:38991627:GTAA:G	donor_loss	1.0000
22:38992032:A:AG	acceptor_gain	1.0000
22:38992032:A:AT	acceptor_loss	1.0000
22:38992033:G:A	acceptor_loss	1.0000
22:38992033:G:GT	acceptor_gain	1.0000
22:38992033:GA:G	acceptor_gain	1.0000
22:38992033:GAGT:G	acceptor_gain	1.0000
22:38992033:GAGTT:G	acceptor_gain	1.0000
22:38984172:G:GG	donor_gain	0.9900
22:38989452:CACAG:C	acceptor_loss	0.9900
22:38989453:ACAG:A	acceptor_loss	0.9900
22:38989454:CA:C	acceptor_loss	0.9900

AlphaMissense

2533 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:38986300:T:C	F153L	0.986
22:38986302:T:A	F153L	0.986
22:38986302:T:G	F153L	0.986
22:38984118:T:C	F21L	0.985
22:38984120:T:A	F21L	0.985
22:38984120:T:G	F21L	0.985
22:38992036:T:C	F341L	0.985
22:38992038:T:A	F341L	0.985
22:38992038:T:G	F341L	0.985
22:38992057:T:C	F348L	0.984
22:38992059:T:A	F348L	0.984
22:38992059:T:G	F348L	0.984
22:38989479:T:C	F198L	0.983
22:38989481:C:A	F198L	0.983
22:38989481:C:G	F198L	0.983
22:38986321:T:C	F160L	0.982
22:38986323:T:A	F160L	0.982
22:38986323:T:G	F160L	0.982
22:38989491:T:C	F202L	0.981
22:38989493:T:A	F202L	0.981
22:38989493:T:G	F202L	0.981
22:38984106:T:C	F17L	0.979
22:38984108:C:A	F17L	0.979
22:38984108:C:G	F17L	0.979
22:38985956:T:C	F107L	0.979
22:38985958:C:A	F107L	0.979
22:38985958:C:G	F107L	0.979
22:38991494:T:C	F296L	0.979
22:38991496:C:A	F296L	0.979
22:38991496:C:G	F296L	0.979

dbSNP variants (sampled 300 via entrez): RS1000852159 (22:38985105 G>A), RS1000947215 (22:38991436 T>C), RS1001509097 (22:38985419 G>A), RS1001538797 (22:38988523 A>C,G), RS1001877588 (22:38989999 G>C), RS1002540104 (22:38987093 C>T), RS1002613787 (22:38986851 G>A), RS1002745834 (22:38980469 T>C), RS1002776161 (22:38981356 A>G), RS1003567345 (22:38981225 G>A,T), RS1003596874 (22:38981490 C>A,G,T), RS1004362190 (22:38987118 A>C,G), RS1004451294 (22:38993233 G>A,C), RS1004889908 (22:38982830 C>T), RS1004959740 (22:38988997 C>T)

Disease associations

OMIM: gene MIM:607110 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002408_17	Response to methotrexate in juvenile idiopathic arthritis	9.000000e-08
GCST004988_271	Breast cancer	5.000000e-12
GCST007100_13	Asthma exacerbations in inhaled corticosteroid treatment	3.000000e-06
GCST007100_14	Asthma exacerbations in inhaled corticosteroid treatment	5.000000e-06
GCST007100_16	Asthma exacerbations in inhaled corticosteroid treatment	3.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007614	asthma exacerbation measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523487 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	decreases expression, increases expression, affects expression, affects cotreatment	6
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	6
Benzo(a)pyrene	increases expression, decreases methylation	5
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	4
Cyclosporine	decreases expression, increases expression	4
bisphenol A	decreases expression, increases expression	2
entinostat	increases expression, affects cotreatment	2
Acetaminophen	decreases expression, increases expression	2
Arsenic	affects expression, affects response to substance, decreases methylation, increases expression, affects cotreatment (+6 more)	2
Hydrogen Peroxide	decreases expression	2
Nickel	increases expression	2
Progesterone	affects cotreatment, affects expression, decreases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	2
Aflatoxin B1	increases expression, increases methylation	2
aristolochic acid I	increases expression	1
trichostatin A	increases expression	1
arsenite	affects binding, increases reaction	1
sulforaphane	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
benzo(e)pyrene	increases methylation	1
ferrous chloride	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
nickel sulfate	increases expression	1
diallyl trisulfide	decreases expression	1
chromium hexavalent ion	increases abundance, decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4419773	Binding	Inhibition of recombinant APOBEC3B (unknown origin) expressed in HEK293 cells assessed as reduction in cytosine deaminase activity using 5’-6-FAM and 3’-TAMRA quench molecule tagged cytosine-containing single-stranded DNA substrate incubate	Small molecule inhibitors of apobec3g and apobec3b

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A0HC	THP18-deltaA3A/B	Cancer cell line	Male
CVCL_B7W0	Abcam Raji APOBEC3B KO	Cancer cell line	Male
CVCL_B9WI	Abcam THP-1 APOBEC3B KO	Cancer cell line	Male
CVCL_C6YJ	Abcam PC-3 APOBEC3B KO	Cancer cell line	Male
CVCL_D8HE	Ubigene HCT 116 APOBEC3B KO	Cancer cell line	Male

Clinical trials (associated diseases)

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