APOBEC3A

Summary

APOBEC3A (apolipoprotein B mRNA editing enzyme catalytic subunit 3A, HGNC:17343) is a protein-coding gene on chromosome 22q13.1, encoding DNA dC->dU-editing enzyme APOBEC-3A (P31941). DNA deaminase (cytidine deaminase) with restriction activity against viruses, foreign DNA and mobility of retrotransposons.

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. The protein encoded by this gene lacks the zinc binding activity of other family members. The protein plays a role in immunity, by restricting transmission of foreign DNA such as viruses. One mechanism of foreign DNA restriction is deamination of foreign double-stranded DNA cytidines to uridines, which leads to DNA degradation. However, other mechanisms are also thought to be involved, as anti-viral effect is not dependent on deaminase activity. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 200315 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 31 total — 1 likely-pathogenic
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_145699

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17343
Approved symbol	APOBEC3A
Name	apolipoprotein B mRNA editing enzyme catalytic subunit 3A
Location	22q13.1
Locus type	gene with protein product
Status	Approved
Aliases	ARP3, PHRBN
Ensembl gene	ENSG00000128383
Ensembl biotype	protein_coding
OMIM	607109
Entrez	200315

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000249116, ENST00000402255, ENST00000488758, ENST00000495988

RefSeq mRNA: 2 — MANE Select: NM_145699 NM_001270406, NM_145699

CCDS: CCDS13981

Canonical transcript exons

ENST00000249116 — 5 exons

Exon	Start	End
ENSE00003473821	38959542	38959686
ENSE00003843784	38957609	38957720
ENSE00003850593	38962495	38963184
ENSE00003894273	38961387	38961681
ENSE00003895723	38962098	38962213

Expression profiles

Bgee: expression breadth ubiquitous, 213 present calls, max score 98.99.

FANTOM5 (CAGE): breadth broad, TPM avg 25.1058 / max 2732.6737, expressed in 285 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
192283	21.7276	257
192281	3.1985	137
192284	0.1798	50

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	98.99	gold quality
mononuclear cell	CL:0000842	98.97	gold quality
leukocyte	CL:0000738	98.89	gold quality
palpebral conjunctiva	UBERON:0001812	98.70	gold quality
granulocyte	CL:0000094	98.69	gold quality
blood	UBERON:0000178	98.21	gold quality
spleen	UBERON:0002106	94.49	gold quality
periodontal ligament	UBERON:0008266	93.70	gold quality
bone marrow cell	CL:0002092	92.44	gold quality
right lung	UBERON:0002167	92.37	gold quality
bone marrow	UBERON:0002371	92.29	gold quality
amniotic fluid	UBERON:0000173	91.62	gold quality
upper lobe of left lung	UBERON:0008952	87.83	gold quality
eye	UBERON:0000970	87.19	gold quality
lower esophagus mucosa	UBERON:0035834	87.09	gold quality
trabecular bone tissue	UBERON:0002483	86.57	gold quality
cervix epithelium	UBERON:0004801	86.08	gold quality
upper lobe of lung	UBERON:0008948	85.84	gold quality
gingival epithelium	UBERON:0001949	85.56	gold quality
cervix squamous epithelium	UBERON:0006922	85.30	gold quality
vermiform appendix	UBERON:0001154	83.02	gold quality
gingiva	UBERON:0001828	82.39	gold quality
gall bladder	UBERON:0002110	81.06	gold quality
mucosa of transverse colon	UBERON:0004991	80.63	gold quality
buccal mucosa cell	CL:0002336	80.05	gold quality
mucosa of urinary bladder	UBERON:0001259	79.63	gold quality
epithelium of nasopharynx	UBERON:0001951	79.03	gold quality
nasopharynx	UBERON:0001728	79.02	gold quality
oral cavity	UBERON:0000167	76.32	gold quality
lung	UBERON:0002048	76.24	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-9801	yes	8.74
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TET1

miRNA regulators (miRDB)

22 targeting APOBEC3A, 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-4775	99.98	75.00	6394
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-3152-3P	99.10	66.35	678
HSA-MIR-29A-5P	99.08	68.59	1813
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-1207-3P	98.99	66.22	1532
HSA-MIR-29B-1-5P	98.86	68.35	1364
HSA-MIR-935	98.82	69.36	1072
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-7843-3P	98.31	67.94	803
HSA-MIR-4303	98.01	68.13	2304
HSA-MIR-5581-5P	97.91	66.50	965
HSA-MIR-890	97.47	68.67	982

Literature-anchored findings (GeneRIF, showing 40)

• APOBEC3A inhibits intracisternal A-particle retrotransposition via a novel mechanism. (PMID:16407327)
• results suggest that the A3G N-terminal domain carries determinants important for targeting the protein to viral NPCs. Transfer of this domain to A3A results in A3A targeting to viral NPCs and confers antiviral activity. (PMID:17727729)
• 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)
• study provides evidence of editing of human papillomavirus 1a and 16 DNA by APOBEC3 in plantar warts and precancerous cervix biopsies (PMID:18403710)
• results demonstrate that deaminase activity is not necessary for the antiviral activity of APOBEC3A against parvoviruses (PMID:19461882)
• 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)
• APOBEC3A is induced by interferon following DNA detection, and it deaminates foreign double-stranded DNA cytidines to uridines. (PMID:20062055)
• A single-point mutation in SIV Vpx (H82A) abrogated binding to APOBEC3A and single-round infection of monocytes by HIV-1. (PMID:20178977)
• Deaminase activity of APOBEC3A isoforms in monocytes and macrophages may play an important role in host defense against viruses. (PMID:20615867)
• THese results revealed an essential functional role for the predicted single-stranded DNA-docking groove located around the APOBEC3A catalytic site. (PMID:21123384)
• Use of the protein fragment complementation assay is a simple and reliable technique for the assessment of HIV-1 protein Vif interaction with APOBEC3 cytidine deaminase. (PMID:21279453)
• APOBEC3A can activate the DNA damage response and cause cell-cycle arrest. (PMID:21460793)
• The authors show that infrequent editing of HIV-1 reverse transcripts can also be mediated by APOBEC3 proteins supplied by the targets of infection. (PMID:21957290)
• 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)
• Data suggest that positive selection was apparent along a few branches which differed compared to positive selection in the carboxy-terminal of APOBEC3G (A3G) that clusters with APOBEC3A (A3A) among cytidine deaminases. (PMID:22272271)
• The authors show that APOBEC3A, APOBEC3B, and APOBEC3H haplotype 2 (A3H hapII) acted as potent inhibitors of HTLV-1. (PMID:22457529)
• While APOBEC3A was a strong deaminator of both C and 5-methylcytosine, AID and APOBEC3G were much weaker in their ability to deaminate this modified base. (PMID:22798497)
• APOBEC3A was able to deaminate dsDNA undergoing transcription suggests a genomic cost of a deamination-based retroviral restriction system. (PMID:22822074)
• Decreases in APOBAC3A and APOBAC3C in the cortex of psychotic patients support the hypothesis that an epigenetic misregulation of gene expression may be operative in the pathogenesis of psychotic disorders. (PMID:22948384)
• Tribbles 3 protects nuclear DNA from cytidine deamination by APOBEC3A (PMID:22977230)
• results implicate APOBEC3B/A in breast cancer hypermutation and give insight into the mechanism of kataegis (PMID:23599896)
• Monocytic cells use a cytoplasmic retention mechanism to control APOBEC3A and avert genotoxicity during innate immune responses. (PMID:23640892)
• These results afford novel mechanistic insights into APOBEC3A-mediated deamination. (PMID:23695684)
• A3A among all human PCDs can deaminate 5-methylcytidine in a variety of single stranded DNA substrates both in vitro and in transfected cells. (PMID:23840298)
• APOBEC3A induction may generate many of the lesions typical of a cancer genome. (PMID:23977391)
• Data indicate that APOBEC3A (Apo3A) activity and C motif deamination specificity exhibit a striking dependence on pH. (PMID:23979356)
• Examination of deaminase and nucleic acid binding properties of human APOBEC3A in the context of its 3D structure. (PMID:24163103)
• APOBEC3 deaminases upregulated by IFN-beta induce E2 hypermutation of HPV16 in cervical keratinocytes. (PMID:24227842)
• The APOBEC3A-APOBEC3B germline deletion allele confers cancer susceptibility through increased activity of APOBEC-dependent mutational processes. (PMID:24728294)
• We identified a recognition loop that altered APOBEC3A sequence specificity. (PMID:24827831)
• data provide a mechanistic explanation of how the APOBEC3A cytidine deaminase protein can inhibit L1 retrotransposition (PMID:24843014)
• Both A3A and A3G restrict infection by murine retroviruses: A3G was packaged into virions and caused extensive deamination of the retrovirus genomes while A3A was not packaged and instead restricted infection when expressed in target cells. (PMID:24851906)
• AFM image analyses reveal A3A binding to single-stranded DNA, and that this interaction becomes most evident ( approximately 80% complex yield) at high protein-to-DNA ratios (at least 100ratio1). A3A is predominantly monomeric when bound to single-stranded DNA. (PMID:24905100)
• Chimeric A3A mRNA resulting from DeltaA3B was more stable, resulting in higher intracellular A3A levels and greater DNA damage. (PMID:25298230)
• Collectively, these findings suggest that APOBEC3A acts as a restriction factor against human papillomavirus infection, but the induction of this restriction mechanism by human papillomavirus may come at a cost to the host by promoting cancer mutagenesis. (PMID:25355878)
• Expression of APOBEC3A or 3C in 293FT cells reduced the infectivity of HPV16 pseudovirions. The reduced infectivity of virions assembled in the presence of APOBEC3A, but not 3C, was attributed to decreased copy number of the encapsidated reporter plasmid. (PMID:25576866)
• The role of APOBEC3A in mediating this change was confirmed by A3A overexpression in Fujioka cells, which led to a significant increase in WT1 c.1303G>A mRNA editing. (PMID:25807502)
• This study demonstrates the cellular RNA editing activity of a member of the APOBEC3 family of innate restriction factors and expands the understanding of C>U RNA editing in mammals. (PMID:25898173)
• Structural studies show that specific binding of single-stranded DNA is regulated by the cooperative dimerization of APOBEC3A. (PMID:25914058)
• These results indicate that the mechanisms of APOBEC3 restriction of Koala Retro Virus by humanA3G and mouseA3 differ (deamination dependent vs. independent) and glyco-gag does not play a role in the restriction. (PMID:26253512)

Cross-species orthologs

0 orthologs

Paralogs (9): APOBEC3H (ENSG00000100298), APOBEC1 (ENSG00000111701), AICDA (ENSG00000111732), APOBEC2 (ENSG00000124701), APOBEC3F (ENSG00000128394), APOBEC3B (ENSG00000179750), APOBEC3G (ENSG00000239713), APOBEC3D (ENSG00000243811), APOBEC3C (ENSG00000244509)

Protein

Protein identifiers

DNA dC->dU-editing enzyme APOBEC-3A — P31941 (reviewed: P31941)

Alternative names: Phorbolin-1

All UniProt accessions (2): P31941, A0A0K0MJ49

UniProt curated annotations — full annotation on UniProt →

Function. DNA deaminase (cytidine deaminase) with restriction activity against viruses, foreign DNA and mobility of retrotransposons. Exhibits antiviral activity against adeno-associated virus (AAV) and human T-cell leukemia virus type 1 (HTLV-1) and may inhibit the mobility of LTR and non-LTR retrotransposons. Selectively targets single-stranded DNA and can deaminate both methylcytosine and cytosine in foreign DNA. Can induce somatic hypermutation in the nuclear and mitochondrial DNA. May also play a role in the epigenetic regulation of gene expression through the process of active DNA demethylation.

Subunit / interactions. Interacts with AGO2. Interacts with TRIB3 (via N-terminus).

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Expressed in peripheral leukocytes with higher expression in CD14-positive phagocytic cells. Highly expressed in keratinocytes and in periphery blood monocytes. Also detected in non-lymphoid tissues including lung and adipose tissues. Found at high levels in colorectal adenocarcinoma, Burkitt’s lymphoma and chronic myelogenous leukemia.

Induction. Up-regulated by interferon and CpG single-stranded DNA (at protein level).

Miscellaneous. It is one of seven related genes or pseudogenes found in a cluster, thought to result from gene duplication, on chromosome 22. Enzymatically active. Enzymatically active.

Similarity. Belongs to the cytidine and deoxycytidylate deaminase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P31941-1	1, Phorbolin-1	yes
P31941-2	2

RefSeq proteins (2): NP_001257335, NP_663745* (*=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 (41 total): mutagenesis site 15, strand 9, helix 7, binding site 3, turn 2, chain 1, domain 1, active site 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
8FIK	X-RAY DIFFRACTION	1.91
8FIL	X-RAY DIFFRACTION	2.01
5KEG	X-RAY DIFFRACTION	2.2
8FIM	X-RAY DIFFRACTION	2.22
8FIJ	X-RAY DIFFRACTION	2.8
4XXO	X-RAY DIFFRACTION	2.84
8FII	X-RAY DIFFRACTION	2.94
5SWW	X-RAY DIFFRACTION	3.15
2M65	SOLUTION NMR
7D3V	SOLUTION NMR
7D3W	SOLUTION NMR
7D3X	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P31941-F1	87.64	0.66

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 72 (proton donor)

Ligand- & substrate-binding residues (3): 70; 101; 106

Mutagenesis-validated functional residues (15):

Position	Phenotype
30	altered deaminase activity and restriction activity towards genetic invaders.
57	altered deaminase activity and restriction activity towards genetic invaders.
60	altered deaminase activity and restriction activity towards genetic invaders.
69	altered deaminase activity and restriction activity towards genetic invaders.
70	altered deaminase activity.
72	altered deaminase activity and restriction activity towards genetic invaders.
98	altered deaminase activity and restriction activity towards genetic invaders.
106	altered deaminase activity.
128	altered deaminase activity and restriction activity towards genetic invaders.
130	altered deaminase activity and restriction activity towards genetic invaders.
131	no effect on deaminase activity despite an altered restriction activity towards genetic invaders.
133	altered deaminase activity and restriction activity towards genetic invaders.
136	altered deaminase activity and restriction activity towards genetic invaders.
28	no effect on deaminase activity despite an altered restriction activity towards genetic invaders.
29	altered deaminase activity and restriction activity towards genetic invaders.

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: 188 (showing top): ZHAN_MULTIPLE_MYELOMA_MF_UP, GOBP_NEGATIVE_REGULATION_OF_VIRAL_PROCESS, GOBP_DNA_MODIFICATION, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_RNA_MODIFICATION, GNF2_S100A4, GOBP_VIRAL_GENOME_REPLICATION, GOBP_VIRAL_LIFE_CYCLE, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GOBP_TRANSCRIPTION_INITIATION_AT_RNA_POLYMERASE_II_PROMOTER, GNF2_HCK, GOBP_DEFENSE_RESPONSE_TO_VIRUS, GOBP_CHROMATIN_REMODELING, GOBP_REGULATION_OF_VIRAL_GENOME_REPLICATION, GOBP_NEGATIVE_REGULATION_OF_VIRAL_GENOME_REPLICATION

GO Biological Process (10): transposable element silencing (GO:0010526), cytidine to uridine editing (GO:0016554), positive regulation of gene expression via chromosomal CpG island demethylation (GO:0044029), clearance of foreign intracellular DNA (GO:0044355), negative regulation of viral genome replication (GO:0045071), 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)

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
transcription initiation-coupled chromatin remodeling	1
clearance of foreign intracellular nucleic acids	1
viral genome replication	1
regulation of viral genome replication	1
negative regulation of viral process	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
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

1272 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
APOBEC3A	CDA	P32320	917
APOBEC3A	APOBEC4	Q8WW27	800
APOBEC3A	APOB	P04114	766
APOBEC3A	UNG	P13051	683
APOBEC3A	CUL5	Q93034	606
APOBEC3A	SAMHD1	Q9Y3Z3	605
APOBEC3A	CBX6	O95503	543
APOBEC3A	ADAR	P55265	520
APOBEC3A	APOBEC3H	Q6NTF7	518
APOBEC3A	PDGFB	P01127	497
APOBEC3A	IFNA13	P01562	480
APOBEC3A	APOBEC3F	Q8IUX4	471
APOBEC3A	APOBEC3C	Q9NRW3	470
APOBEC3A	BST2	Q10589	448
APOBEC3A	A1CF	Q9NQ94	448

IntAct

20 interactions, top by confidence:

A	B	Type	Score
C	APOBEC3A	psi-mi:“MI:0915”(physical association)	0.560
C	APOBEC3A	psi-mi:“MI:2364”(proximity)	0.560
STAMBP	APOBEC3A	psi-mi:“MI:0915”(physical association)	0.560
APOBEC3A	HAGH	psi-mi:“MI:0915”(physical association)	0.560
APOBEC3A	APOBEC3A	psi-mi:“MI:0407”(direct interaction)	0.440
	APOBEC3A	psi-mi:“MI:0985”(deamination reaction)	0.440
CDK15	A2ML1	psi-mi:“MI:0914”(association)	0.350
DDX19B	IGLL5	psi-mi:“MI:0914”(association)	0.350
AGPAT1	A2ML1	psi-mi:“MI:0914”(association)	0.350
SIK1	KLK10	psi-mi:“MI:0914”(association)	0.350
H2AB1	NRDC	psi-mi:“MI:0914”(association)	0.350
SF3B1	RBM10	psi-mi:“MI:0914”(association)	0.350
SF3B1	FAM83G	psi-mi:“MI:0914”(association)	0.350
APOBEC3A	STAMBP	psi-mi:“MI:0915”(physical association)	0.000
APOBEC3A	HAGH	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (15): APOBEC3A (Affinity Capture-MS), APOBEC3A (Affinity Capture-MS), APOBEC3A (Affinity Capture-Western), CUL2 (Affinity Capture-Western), TRIB3 (Reconstituted Complex), Trib3 (Reconstituted Complex), APOBEC3A (Synthetic Lethality), APOBEC3A (Two-hybrid), APOBEC3A (Two-hybrid), APOBEC3A (Affinity Capture-MS), APOBEC3A (Affinity Capture-MS), APOBEC3A (Affinity Capture-MS), APOBEC3A (Affinity Capture-MS), APOBEC3A (Affinity Capture-Western), VHL (Affinity Capture-Western)

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
CUL2	“down-regulates quantity by destabilization”	APOBEC3A	ubiquitination
APOBEC3A	up-regulates	“Clearance_of_foreign intracellular_DNA”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	21
Likely benign	4
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
816479	GRCh37/hg19 22q13.1(chr22:38431917-39392250)x1	Likely pathogenic

SpliceAI

657 predictions. Top by Δscore:

Variant	Effect	Δscore
22:38961382:TCTA:T	acceptor_loss	1.0000
22:38961384:TA:T	acceptor_loss	1.0000
22:38961385:A:AG	acceptor_gain	1.0000
22:38961385:A:G	acceptor_loss	1.0000
22:38961385:AG:A	acceptor_gain	1.0000
22:38961386:G:GT	acceptor_gain	1.0000
22:38961386:GG:G	acceptor_gain	1.0000
22:38961386:GGC:G	acceptor_gain	1.0000
22:38961386:GGCTA:G	acceptor_gain	1.0000
22:38961677:CGATG:C	donor_gain	1.0000
22:38961678:GATG:G	donor_gain	1.0000
22:38961678:GATGG:G	donor_gain	1.0000
22:38961679:ATG:A	donor_gain	1.0000
22:38961679:ATGG:A	donor_loss	1.0000
22:38961680:TG:T	donor_gain	1.0000
22:38961680:TGGT:T	donor_loss	1.0000
22:38961681:GG:G	donor_gain	1.0000
22:38961681:GGTA:G	donor_loss	1.0000
22:38961682:G:GG	donor_gain	1.0000
22:38961682:GTAA:G	donor_loss	1.0000
22:38961683:T:A	donor_loss	1.0000
22:38962095:CAGAA:C	acceptor_gain	1.0000
22:38962096:A:AC	acceptor_loss	1.0000
22:38962096:A:AG	acceptor_gain	1.0000
22:38962097:G:GC	acceptor_gain	1.0000
22:38962097:GA:G	acceptor_gain	1.0000
22:38962097:GAA:G	acceptor_gain	1.0000
22:38962097:GAAT:G	acceptor_gain	1.0000
22:38962097:GAATT:G	acceptor_gain	1.0000
22:38952847:ACAGG:A	donor_loss	0.9900

AlphaMissense

1326 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:38962121:T:C	F165L	0.965
22:38962123:T:A	F165L	0.965
22:38962123:T:G	F165L	0.965
22:38962100:T:C	F158L	0.955
22:38962102:T:A	F158L	0.955
22:38962102:T:G	F158L	0.955
22:38959576:T:C	F22L	0.952
22:38959578:T:A	F22L	0.952
22:38959578:T:G	F22L	0.952
22:38961549:T:C	F113L	0.949
22:38961551:C:A	F113L	0.949
22:38961551:C:G	F113L	0.949
22:38961495:T:C	F95L	0.948
22:38961497:C:A	F95L	0.948
22:38961497:C:G	F95L	0.948
22:38961507:A:C	S99R	0.945
22:38961509:C:A	S99R	0.945
22:38961509:C:G	S99R	0.945
22:38959564:T:C	F18L	0.943
22:38959566:C:A	F18L	0.943
22:38959566:C:G	F18L	0.943
22:38962145:T:C	F173L	0.936
22:38962147:C:A	F173L	0.936
22:38962147:C:G	F173L	0.936
22:38961671:G:A	M153I	0.933
22:38961671:G:C	M153I	0.933
22:38961671:G:T	M153I	0.933
22:38959672:T:C	F54L	0.923
22:38959674:T:A	F54L	0.923
22:38959674:T:G	F54L	0.923

dbSNP variants (sampled 300 via entrez): RS1000213836 (22:38960249 A>G), RS1000706253 (22:38955854 G>A), RS1000924375 (22:38961754 G>A), RS1001254289 (22:38958881 G>A), RS1001421218 (22:38957523 G>A), RS1001618695 (22:38959120 T>C), RS1004108511 (22:38963378 GCA>G), RS1004342071 (22:38957898 G>A), RS1004542211 (22:38963241 C>T), RS1004673603 (22:38959145 G>A,C), RS1005272450 (22:38956831 C>T), RS1005346202 (22:38956587 A>C), RS1006412868 (22:38955827 T>G), RS1006860664 (22:38962346 C>T), RS1007277557 (22:38956506 G>A)

Disease associations

OMIM: gene MIM:607109 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000842_7	Bladder cancer	8.000000e-12
GCST002240_10	Bladder cancer	1.000000e-11
GCST004988_271	Breast cancer	5.000000e-12
GCST90002404_412	Red cell distribution width	1.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009188	Red cell distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1741179 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 16,679 (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
CHEMBL3561076	TRIMETAZIDINE DIHYDROCHLORIDE	4	280
CHEMBL474579	CEFOTETAN	4	15,647
CHEMBL1716983	ENISAMIUM IODIDE	3	1
CHEMBL1257065	STILONIUM IODIDE	2	751

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

Binding affinities (BindingDB)

490 measured of 714 human assays (753 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
MLS000082581	EC50	0.0948 nM
5-cyclopentylidene-2-sulfanylidene-1,3-thiazolidin-4-one	IC50	240 nM
4-amino-3-(4-methylphenyl)-5-[(4-methyl-1-piperazinyl)carbonyl]-1,3-thiazole-2(3H)-thione	IC50	250 nM
6-bromo-N-piperonyl-pyrazolo[1,5-a]pyrimidine-2-carboxamide	IC50	363 nM
MLS000689390	EC50	880 nM
MLS001208265	IC50	892 nM
3-chloranyl-N-(3-morpholin-4-ylpropyl)-6-nitro-1-benzothiophene-2-carboxamide	EC50	950 nM
trimethyl-[2-[oxo-(1-phenylcyclopentyl)methoxy]ethyl]ammonium;iodide	IC50	1060 nM
MLS000036597	IC50	1070 nM
MLS001212885	IC50	1080 nM
SMR000305231	IC50	1140 nM
1-ethyl-5-methyl-4-[(phenylsulfonyl)methyl]-1,3-dihydro-2H-imidazol-2-one	IC50	1230 nM
cid_6294434	IC50	1240 nM
cid_6603239	IC50	1300 nM
cid_16682258	IC50	1310 nM
ethyl 5-(diethylamino)-2-hydroxyimino-pentanoate;iodanylmethane	IC50	1350 nM
SMR000279529	IC50	1390 nM
SMR000283917	IC50	1440 nM
3-pyridinecarboxylic acid (3-acetyl-4-oxido-2-quinoxalin-4-iumyl)methyl ester	IC50	1480 nM
2-{(E)-2-[3-Methoxy-4-(o-tolylcarbamoyl-methoxy)-phenyl]-vinyl}-1-methyl-pyridinium	IC50	1560 nM
2-[[5-[[2-(3-chloroanilino)-4-thiazolyl]methyl]-4-(3-methoxypropyl)-1,2,4-triazol-3-yl]thio]acetic acid cyclohexyl ester	IC50	1560 nM
SMR000198590	IC50	1580 nM
1-phenyl-1-cyclopentanecarboxylic acid 3-(4-methyl-4-morpholin-4-iumyl)propyl ester;iodide	IC50	1610 nM
SMR000306192	IC50	1610 nM
MLS001183995	IC50	1610 nM
3-[(2-methyl-5-oxidanylidene-3-phenyl-4H-imidazol-4-yl)diazenyl]benzoic acid	EC50	1640 nM
MLS000065559	IC50	1640 nM
MLS000565397	IC50	1660 nM
SMR000173748	IC50	1670 nM
2-(4,6-dimethyl-3-oxidanylidene-[1,2]thiazolo[5,4-b]pyridin-2-yl)-N-(3-fluorophenyl)ethanamide	EC50	1720 nM
MLS000689393	EC50	1750 nM
1-cyclohexyloxy-3-(2-ethyl-3-methyl-benzimidazol-3-ium-1-yl)propan-2-ol;iodide	IC50	1750 nM
3,4-dimethyl-1-(2H-tetrazol-5-yl)-6-pyrano[2,3-c]pyrazolone	IC50	1760 nM
(1,3-dimethyl-1H-imidazol-3-ium-2-yl)methyl methylcarbamate	IC50	1760 nM
1-O-tert-butyl 2-O-[2-oxo-2-(4-phenylphenyl)ethyl] 4-hydroxypyrrolidine-1,2-dicarboxylate	IC50	1790 nM
1-heptylpyridin-4-imine;hydroiodide	IC50	1830 nM
cid_14262872	IC50	1850 nM
2-Cyano-3-(2-methyl-1H-indol-3-yl)-N-(1-phenyl-ethyl)-acrylamide	IC50	1870 nM
[(2Z)-2-(1,3-dioxolan-4-ylidene)ethyl]-trimethylammonium;iodide	IC50	1890 nM
SMR000518608	IC50	1890 nM
MLS000333810	IC50	1910 nM
cid_6473547	IC50	1910 nM
MLS000688171	IC50	1930 nM
(8S)-7-(3,3-diphenylpropanoyl)-3-[3-(2-methylprop-2-enoylamino)phenyl]-1-oxa-2,7-diazaspiro[4.4]non-2-ene-8-carboxamide	EC50	1940 nM
MLS000698163	IC50	1960 nM
MLS000408951	IC50	1970 nM
MLS000110102	IC50	2010 nM
MLS000037873	IC50	2020 nM
cid_2237442	IC50	2030 nM
MLS000712970	IC50	2030 nM

ChEMBL bioactivities

372 potent at pChembl≥5 of 495 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.05	IC50	892	nM	CHEMBL1586607
5.97	IC50	1060	nM	CHEMBL1362702
5.97	IC50	1080	nM	CHEMBL589711
5.97	IC50	1070	nM	CHEMBL1503187
5.94	IC50	1140	nM	CHEMBL3196851
5.92	IC50	1190	nM	CHEMBL255881
5.92	IC50	1210	nM	CHEMBL255881
5.91	IC50	1240	nM	CHEMBL1338153
5.90	IC50	1270	nM	CHEMBL1704847
5.89	IC50	1300	nM	CHEMBL1577127
5.88	IC50	1310	nM	CHEMBL1543727
5.87	IC50	1350	nM	CHEMBL1333873
5.87	IC50	1350	nM	CHEMBL3207528
5.86	IC50	1390	nM	CHEMBL1711351
5.84	IC50	1440	nM	CHEMBL1467678
5.83	IC50	1480	nM	CHEMBL1408132
5.82	IC50	1530	nM	CHEMBL1501432
5.82	IC50	1510	nM	CHEMBL1389035
5.81	IC50	1550	nM	CHEMBL1582492
5.81	IC50	1560	nM	CHEMBL1342158
5.80	IC50	1580	nM	CHEMBL1325780
5.79	IC50	1640	nM	CHEMBL1585158
5.79	IC50	1610	nM	CHEMBL1599302
5.79	IC50	1610	nM	CHEMBL1389793
5.79	IC50	1610	nM	CHEMBL1327723
5.78	IC50	1670	nM	CHEMBL1485727
5.78	IC50	1660	nM	CHEMBL1499690
5.77	IC50	1700	nM	CHEMBL1447034
5.76	IC50	1750	nM	CHEMBL1558595
5.76	IC50	1750	nM	CHEMBL1341547
5.75	IC50	1790	nM	CHEMBL1564678
5.75	IC50	1760	nM	CHEMBL1403277
5.75	IC50	1760	nM	CHEMBL1379279
5.74	IC50	1830	nM	CHEMBL590706
5.73	IC50	1870	nM	CHEMBL1523040
5.73	IC50	1850	nM	GLAUCINE METHIODIDE
5.72	IC50	1910	nM	CHEMBL1377153
5.72	IC50	1910	nM	CHEMBL1559194
5.72	IC50	1890	nM	CHEMBL1375102
5.72	IC50	1890	nM	CHEMBL1733996
5.72	IC50	1890	nM	CHEMBL1525928
5.71	IC50	1960	nM	CHEMBL1536626
5.71	IC50	1930	nM	CHEMBL1309967
5.71	IC50	1970	nM	CHEMBL1547022
5.71	IC50	1970	nM	CHEMBL1405185
5.71	IC50	1930	nM	DIMETHYLPHENYLPIPERAZINIUM IODIDE
5.71	IC50	1970	nM	CHEMBL1503015
5.71	IC50	1930	nM	CHEMBL1503187
5.70	IC50	2010	nM	CHEMBL1551307
5.70	IC50	2020	nM	CHEMBL1452833

PubChem BioAssay actives

4 with measured affinity, of 4 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-(5-methylfuran-2-yl)-N-(5-pyridin-4-yl-1,3,4-thiadiazol-2-yl)quinoline-4-carboxamide	1245743: Inhibition of APOBEC3A (unknown origin) by fluorescence-based ssDNA C-to-U deaminase assay	ic50	2.8000	uM

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression, increases expression	2
Nickel	decreases expression, increases expression	2
triphenyl phosphate	affects expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
gadodiamide	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
(+)-JQ1 compound	decreases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Air Pollutants, Occupational	decreases expression	1
Benzo(a)pyrene	decreases expression	1
Lipopolysaccharides	increases expression, affects response to substance	1
Ozone	affects expression, increases abundance	1
Silicon Dioxide	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	decreases expression	1
Valproic Acid	increases methylation	1
Antirheumatic Agents	decreases expression	1
Copper Sulfate	increases expression	1

ChEMBL screening assays

8 unique, capped per target: 4 functional, 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1737903	Functional	PUBCHEM_BIOASSAY: Dose Response confirmation of APOBEC3G DNA Deaminase Inhibitors via a A3A counterscreen. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID493012, AID493028]	PubChem BioAssay data set
CHEMBL3616266	Binding	Inhibition of APOBEC3A (unknown origin) by fluorescence-based ssDNA C-to-U deaminase assay	Oxidative Reactivities of 2-Furylquinolines: Ubiquitous Scaffolds in Common High-Throughput Screening Libraries. — J Med Chem

Cellosaurus cell lines

7 cell lines: 7 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A0HB	THP18-deltaA3A	Cancer cell line	Male
CVCL_A0HC	THP18-deltaA3A/B	Cancer cell line	Male
CVCL_C7ZW	HAP1 APOBEC3A (-) 1	Cancer cell line	Male
CVCL_C7ZX	HAP1 APOBEC3A (-) 2	Cancer cell line	Male
CVCL_C7ZY	HAP1 APOBEC3A (-) 3	Cancer cell line	Male
CVCL_C7ZZ	HAP1 APOBEC3A (-) 4	Cancer cell line	Male
CVCL_E1QN	HAP1 APOBEC3A (-) 5	Cancer cell line	Male

Clinical trials (associated diseases)

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