APOBEC2

Summary

APOBEC2 (apolipoprotein B mRNA editing enzyme catalytic subunit 2, HGNC:605) is a protein-coding gene on chromosome 6p21.1, encoding C->U-editing enzyme APOBEC-2 (Q9Y235). Probable C to U editing enzyme whose physiological substrate is not yet known.

Enables cytidine deaminase activity and identical protein binding activity. Involved in positive regulation of gene expression via chromosomal CpG island demethylation. Acts upstream of or within cytidine to uridine editing. Predicted to be active in cytoplasm and nucleus.

Source: NCBI Gene 10930 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 36 total
• MANE Select transcript: NM_006789

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:605
Approved symbol	APOBEC2
Name	apolipoprotein B mRNA editing enzyme catalytic subunit 2
Location	6p21.1
Locus type	gene with protein product
Status	Approved
Aliases	ARCD1, ARP1
Ensembl gene	ENSG00000124701
Ensembl biotype	protein_coding
OMIM	604797
Entrez	10930

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000244669, ENST00000899065

RefSeq mRNA: 1 — MANE Select: NM_006789 NM_006789

CCDS: CCDS4848

Canonical transcript exons

ENST00000244669 — 3 exons

Exon	Start	End
ENSE00000849850	41053202	41053478
ENSE00000849851	41061328	41061892
ENSE00000849852	41064101	41064891

Expression profiles

Bgee: expression breadth ubiquitous, 189 present calls, max score 99.77.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 4.0319 / max 892.6586, expressed in 130 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
67725	2.2516	102
67729	1.0673	82
67727	0.3130	63
67726	0.1933	38
67730	0.1724	35
67728	0.0343	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.77	gold quality
biceps brachii	UBERON:0001507	99.50	gold quality
triceps brachii	UBERON:0001509	99.41	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.40	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.28	gold quality
gluteal muscle	UBERON:0002000	99.24	gold quality
diaphragm	UBERON:0001103	99.23	gold quality
vastus lateralis	UBERON:0001379	99.18	gold quality
skeletal muscle tissue	UBERON:0001134	99.15	gold quality
quadriceps femoris	UBERON:0001377	99.13	gold quality
deltoid	UBERON:0001476	98.76	gold quality
apex of heart	UBERON:0002098	98.43	gold quality
gastrocnemius	UBERON:0001388	98.35	gold quality
tibialis anterior	UBERON:0001385	97.92	gold quality
heart right ventricle	UBERON:0002080	97.88	gold quality
heart left ventricle	UBERON:0002084	97.71	gold quality
muscle organ	UBERON:0001630	97.65	gold quality
skeletal muscle organ	UBERON:0014892	97.65	gold quality
cardiac ventricle	UBERON:0002082	97.63	gold quality
left ventricle myocardium	UBERON:0006566	97.27	gold quality
muscle of leg	UBERON:0001383	97.08	gold quality
body of tongue	UBERON:0011876	95.92	gold quality
right atrium auricular region	UBERON:0006631	95.80	gold quality
muscle tissue	UBERON:0002385	95.62	gold quality
cardiac atrium	UBERON:0002081	95.33	gold quality
myocardium	UBERON:0002349	94.41	gold quality
heart	UBERON:0000948	92.32	gold quality
cardiac muscle of right atrium	UBERON:0003379	90.63	gold quality
islet of Langerhans	UBERON:0000006	90.47	gold quality
tongue	UBERON:0001723	87.47	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-81608	yes	7.32
E-ANND-3	yes	4.86
E-HCAD-31	no	3.51

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

45 targeting APOBEC2, 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-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-219A-5P	99.91	73.36	735
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-4782-3P	99.88	73.31	735
HSA-MIR-6766-3P	99.88	73.38	732
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-18A-3P	99.56	65.68	1092
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-4687-3P	99.48	66.41	968
HSA-MIR-6165	99.44	67.12	1389
HSA-MIR-6513-5P	99.43	67.81	1071
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-520F-5P	99.34	70.40	1632
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-4641	99.28	66.64	744
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-6876-3P	98.97	65.69	765
HSA-MIR-6871-5P	98.90	66.67	671
HSA-MIR-626	98.89	66.21	762

Literature-anchored findings (GeneRIF, showing 5)

• crystal structure of APOBEC2 (PMID:17187054)
• 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)
• The APOBEC2 was confirmed to be elevated in the tonsils with IgAN patients, and the gene expression level was negatively related with serum IgG level in overall patients. (PMID:20138841)
• Findings indicate that aberrant APOBEC2 expression causes nucleotide alterations in the transcripts of the specific target gene and could be involved in the development of human hepatocellular carcinoma through hepatic inflammation. (PMID:21469143)
• Expression and prognostic value of APOBEC2 in gastric adenocarcinoma and its association with tumor-infiltrating immune cells. (PMID:38166744)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	apobec2a	ENSDARG00000018881
danio_rerio	apobec2b	ENSDARG00000113992
mus_musculus	Apobec2	ENSMUSG00000040694
rattus_norvegicus	Apobec2	ENSRNOG00000012303

Paralogs (9): APOBEC3H (ENSG00000100298), APOBEC1 (ENSG00000111701), AICDA (ENSG00000111732), APOBEC3A (ENSG00000128383), APOBEC3F (ENSG00000128394), APOBEC3B (ENSG00000179750), APOBEC3G (ENSG00000239713), APOBEC3D (ENSG00000243811), APOBEC3C (ENSG00000244509)

Protein

Protein identifiers

C->U-editing enzyme APOBEC-2 — Q9Y235 (reviewed: Q9Y235)

Alternative names: mRNA(cytosine(6666)) deaminase 2

All UniProt accessions (1): Q9Y235

UniProt curated annotations — full annotation on UniProt →

Function. Probable C to U editing enzyme whose physiological substrate is not yet known. Does not display detectable apoB mRNA editing. Has a low intrinsic cytidine deaminase activity. May play a role in the epigenetic regulation of gene expression through the process of active DNA demethylation.

Subunit / interactions. Homotetramer.

Tissue specificity. Expressed exclusively in heart and skeletal muscle.

Cofactor. Binds 1 Zn(2+) ion per subunit.

Similarity. Belongs to the cytidine and deoxycytidylate deaminase family.

RefSeq proteins (1): NP_006780* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002125	CMP_dCMP_dom	Domain
IPR016193	Cytidine_deaminase-like	Homologous_superfamily
IPR050610	APOBEC_Cyt_Deaminase	Family

Pfam: PF18772

Catalyzed reactions (Rhea), 1 shown:

• cytidine(6666) in apoB mRNA + H2O + H(+) = uridine(6666) in apoB mRNA + NH4(+) (RHEA:21772)

UniProt features (22 total): strand 6, helix 6, binding site 4, chain 1, domain 1, turn 1, region of interest 1, active site 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2NYT	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y235-F1	73.10	0.26

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): 100 (proton donor)

Ligand- & substrate-binding residues (4): 60; 98; 128; 131

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: 136 (showing top): GCANCTGNY_MYOD_Q6, CAGCTG_AP4_Q5, GOBP_MRNA_MODIFICATION, NKX61_01, IRF7_01, GOBP_RNA_MODIFICATION, TGIF_01, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GOBP_TRANSCRIPTION_INITIATION_AT_RNA_POLYMERASE_II_PROMOTER, GATA1_04, TANAKA_METHYLATED_IN_ESOPHAGEAL_CARCINOMA, GOBP_CHROMATIN_REMODELING, GOBP_EPIGENETIC_REGULATION_OF_GENE_EXPRESSION, REACTOME_METABOLISM_OF_RNA, TGGAAA_NFAT_Q4_01

GO Biological Process (5): mRNA processing (GO:0006397), cytidine to uridine editing (GO:0016554), mRNA modification (GO:0016556), positive regulation of gene expression via chromosomal CpG island demethylation (GO:0044029), regulation of macromolecule biosynthetic process (GO:0010556)

GO Molecular Function (6): RNA binding (GO:0003723), cytidine deaminase activity (GO:0004126), identical protein binding (GO:0042802), metal ion binding (GO:0046872), catalytic activity (GO:0003824), hydrolase activity (GO:0016787)

GO Cellular Component (2): nucleus (GO:0005634), 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
mRNA metabolic process	2
RNA processing	1
base conversion or substitution editing	1
RNA modification	1
transcription initiation-coupled chromatin remodeling	1
macromolecule biosynthetic process	1
regulation of biosynthetic process	1
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
protein binding	1
cation binding	1
molecular_function	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

806 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
APOBEC2	APOBEC4	Q8WW27	923
APOBEC2	APOB	P04114	859
APOBEC2	CDA	P32320	840
APOBEC2	UNG	P13051	652
APOBEC2	ADAR	P55265	523
APOBEC2	A1CF	Q9NQ94	518
APOBEC2	TDG	Q13569	514
APOBEC2	ADAT2	Q7Z6V5	487
APOBEC2	CUL5	Q93034	467
APOBEC2	ADARB2	Q9NS39	459
APOBEC2	MBD4	O95243	437
APOBEC2	ADA	P00813	437
APOBEC2	ASMTL	O95671	414
APOBEC2	SRP19	P09132	409
APOBEC2	ELOB	Q15370	403

IntAct

2 interactions, top by confidence:

A	B	Type	Score
APOBEC2	APOBEC2	psi-mi:“MI:0407”(direct interaction)	0.560

BioGRID (2): APOBEC1 (Far Western), APOBEC2 (Cross-Linking-MS (XL-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, P47855, P60704, P60705, Q19Q52, Q1WBT4, Q2PT36, Q3SYR3, Q4VDN5, Q694B4, Q694B5, Q694B6, Q694B7, Q694B8, Q694B9, Q694C0, Q694C1, Q694C2, Q694C4, Q694C5, Q6NTF7, Q75W64, Q7YR23, Q7YR24, Q7YR25, Q8IUX4, Q96AK3, Q99J72, Q9EQP0, Q9GZX7, Q9HC16, Q9NRW3, Q9UH17, Q9WV35, Q9WVE0, Q9Y235, P38483, P41238, P51908

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

339 predictions. Top by Δscore:

Variant	Effect	Δscore
6:41053475:CAGG:C	donor_gain	1.0000
6:41053476:AGG:A	donor_gain	1.0000
6:41053477:GG:G	donor_gain	1.0000
6:41053477:GGG:G	donor_gain	1.0000
6:41053478:GG:G	donor_gain	1.0000
6:41053479:G:GC	donor_loss	1.0000
6:41053479:G:GG	donor_gain	1.0000
6:41053480:T:A	donor_loss	1.0000
6:41061318:T:A	acceptor_gain	1.0000
6:41061326:A:AG	acceptor_gain	1.0000
6:41061327:G:GG	acceptor_gain	1.0000
6:41061327:GA:G	acceptor_gain	1.0000
6:41061865:G:GT	donor_gain	1.0000
6:41061868:G:GG	donor_gain	1.0000
6:41061893:G:GG	donor_gain	1.0000
6:41064099:A:G	acceptor_gain	1.0000
6:41061310:T:TA	acceptor_gain	0.9900
6:41061324:ACAG:A	acceptor_loss	0.9900
6:41061325:CA:C	acceptor_loss	0.9900
6:41061325:CAG:C	acceptor_gain	0.9900
6:41061326:AGA:A	acceptor_gain	0.9900
6:41061327:GAG:G	acceptor_gain	0.9900
6:41061327:GAGA:G	acceptor_gain	0.9900
6:41061847:G:GT	donor_gain	0.9900
6:41064098:A:AG	acceptor_gain	0.9900
6:41064098:AAG:A	acceptor_gain	0.9900
6:41064098:AAGG:A	acceptor_loss	0.9900
6:41064099:A:AG	acceptor_loss	0.9900
6:41064100:G:GA	acceptor_loss	0.9900
6:41061645:T:TA	acceptor_gain	0.9800

AlphaMissense

1472 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:41061356:T:C	F54L	1.000
6:41061358:C:A	F54L	1.000
6:41061358:C:G	F54L	1.000
6:41061390:G:C	R65T	1.000
6:41061390:G:T	R65M	1.000
6:41061391:G:C	R65S	1.000
6:41061391:G:T	R65S	1.000
6:41061572:A:C	S126R	1.000
6:41061574:C:A	S126R	1.000
6:41061574:C:G	S126R	1.000
6:41061357:T:C	F54S	0.999
6:41061362:T:C	F56L	0.999
6:41061363:T:C	F56S	0.999
6:41061364:C:A	F56L	0.999
6:41061364:C:G	F56L	0.999
6:41061370:T:A	N58K	0.999
6:41061370:T:G	N58K	0.999
6:41061377:T:C	Y61H	0.999
6:41061380:A:C	S62R	0.999
6:41061382:T:A	S62R	0.999
6:41061382:T:G	S62R	0.999
6:41061387:G:A	G64E	0.999
6:41061389:A:G	R65G	0.999
6:41061397:G:C	K67N	0.999
6:41061397:G:T	K67N	0.999
6:41061407:T:C	C71R	0.999
6:41061470:G:C	D92H	0.999
6:41061557:T:A	W121R	0.999
6:41061557:T:C	W121R	0.999
6:41061809:T:A	W205R	0.999

dbSNP variants (sampled 300 via entrez): RS1000009656 (6:41054565 TC>T), RS1000191526 (6:41064989 C>T), RS1000415994 (6:41057594 A>C), RS1000463531 (6:41057960 G>A), RS1000597301 (6:41064361 G>T), RS1000609315 (6:41058286 C>A), RS1000843308 (6:41054332 T>C), RS1000873038 (6:41054140 G>A,T), RS1000928374 (6:41064573 G>A), RS1001142508 (6:41061669 A>T), RS1001428773 (6:41060171 C>T), RS1001849740 (6:41060533 A>G), RS1002085329 (6:41056137 TG>T,TGG), RS1002316237 (6:41054902 G>A), RS1002796851 (6:41054787 G>A)

Disease associations

OMIM: gene MIM:604797 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2073016	APOBEC2		0.00	0

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	2
fluorene-9-bisphenol	increases expression	1
CGP 52608	increases reaction, affects binding	1
incobotulinumtoxinA	decreases expression	1
Sunitinib	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Doxorubicin	increases expression	1
Hydrogen Peroxide	affects expression	1
Triclosan	decreases expression	1
Aflatoxin B1	increases methylation	1
beta-Naphthoflavone	decreases expression	1

Clinical trials (associated diseases)

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