APOBEC4

Summary

APOBEC4 (apolipoprotein B mRNA editing enzyme catalytic polypeptide like 4, HGNC:32152) is a protein-coding gene on chromosome 1q25.3, encoding Putative deaminase APOBEC-4 (Q8WW27). Putative deaminase whose physiological substrate is not yet known.

This gene encodes a member of the AID/APOBEC family of polynucleotide (deoxy)cytidine deaminases, which convert cytidine to uridine. Other AID/APOBEC family members are involved in mRNA editing, somatic hypermutation and recombination of immunoglobulin genes, and innate immunity to retroviral infection.

Source: NCBI Gene 403314 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 56 total
• MANE Select transcript: NM_203454

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32152
Approved symbol	APOBEC4
Name	apolipoprotein B mRNA editing enzyme catalytic polypeptide like 4
Location	1q25.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC26594, FLJ25691, RP1-127C7.4
Ensembl gene	ENSG00000173627
Ensembl biotype	protein_coding
OMIM	609908
Entrez	403314

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000308641, ENST00000481562

RefSeq mRNA: 1 — MANE Select: NM_203454 NM_203454

CCDS: CCDS1358

Canonical transcript exons

ENST00000308641 — 2 exons

Exon	Start	End
ENSE00001178499	183646275	183648811
ENSE00001921926	183653072	183653316

Expression profiles

Bgee: expression breadth broad, 48 present calls, max score 87.60.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0699 / max 25.3399, expressed in 20 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
16240	0.0273	8
16239	0.0201	9
16237	0.0113	6
16238	0.0112	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	87.60	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	85.61	gold quality
bronchus	UBERON:0002185	85.50	gold quality
mucosa of paranasal sinus	UBERON:0005030	84.54	gold quality
sperm	CL:0000019	84.31	gold quality
right uterine tube	UBERON:0001302	79.23	gold quality
oviduct epithelium	UBERON:0004804	77.32	gold quality
epithelium of nasopharynx	UBERON:0001951	74.85	silver quality
nasopharynx	UBERON:0001728	74.84	silver quality
left testis	UBERON:0004533	70.66	gold quality
fallopian tube	UBERON:0003889	69.54	gold quality
testis	UBERON:0000473	68.79	gold quality
right testis	UBERON:0004534	68.09	gold quality
nasal cavity mucosa	UBERON:0001826	65.98	gold quality
caput epididymis	UBERON:0004358	56.52	gold quality
right lung	UBERON:0002167	54.43	gold quality
endometrium	UBERON:0001295	52.37	gold quality
adrenal tissue	UBERON:0018303	47.95	silver quality
islet of Langerhans	UBERON:0000006	47.53	gold quality
corpus callosum	UBERON:0002336	47.19	silver quality
colonic epithelium	UBERON:0000397	46.85	gold quality
adult organism	UBERON:0007023	46.56	gold quality
bone marrow cell	CL:0002092	44.98	gold quality
lung	UBERON:0002048	44.45	gold quality
skin of hip	UBERON:0001554	44.28	silver quality
left uterine tube	UBERON:0001303	43.88	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
uterus	UBERON:0000995	41.89	gold quality
sural nerve	UBERON:0015488	41.53	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.14

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

100 targeting APOBEC4, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4534	99.99	66.58	1907
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4671-3P	99.88	72.46	1045
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-373-3P	99.84	70.68	1668

Literature-anchored findings (GeneRIF, showing 3)

• APOBEC4 is expressed primarily in testis which suggests the possibility that it is an editing enzyme for mRNAs involved in spermatogenesis (PMID:16082223)
• 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)
• APOBEC4 was capable of similarly enhancing transcription from a broad spectrum of promoters, regardless of whether they were viral or mammalian (PMID:27249646)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Apobec4	ENSMUSG00000055547
rattus_norvegicus	Apobec4	ENSRNOG00000028089

Protein

Protein identifiers

Putative deaminase APOBEC-4 — Q8WW27 (reviewed: Q8WW27)

Alternative names: Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 4

All UniProt accessions (1): Q8WW27

UniProt curated annotations — full annotation on UniProt →

Function. Putative deaminase whose physiological substrate is not yet known.

Tissue specificity. Predominantly expressed in testis.

Similarity. Belongs to the cytidine and deoxycytidylate deaminase family.

RefSeq proteins (1): NP_982279* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002125	CMP_dCMP_dom	Domain
IPR038953	APOBEC4	Family

Pfam: PF18778

UniProt features (12 total): sequence variant 6, binding site 3, chain 1, domain 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WW27-F1	71.60	0.51

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): 95 (proton donor)

Ligand- & substrate-binding residues (3): 93; 127; 134

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: 62 (showing top): EFC_Q6, MYOD_01, OCT1_B, TAL1BETAE47_01, REACTOME_METABOLISM_OF_RNA, DODD_NASOPHARYNGEAL_CARCINOMA_DN, chr1q25, TAL1BETAITF2_01, OCT_Q6, E47_02, GOBP_MRNA_PROCESSING, CCTNTMAGA_UNKNOWN, REACTOME_MRNA_EDITING_C_TO_U_CONVERSION, REACTOME_MRNA_EDITING, GSE10240_CTRL_VS_IL17_STIM_PRIMARY_BRONCHIAL_EPITHELIAL_CELLS_UP

GO Biological Process (1): mRNA processing (GO:0006397)

GO Molecular Function (3): hydrolase activity (GO:0016787), metal ion binding (GO:0046872), protein binding (GO:0005515)

GO Cellular Component (0):

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
RNA processing	1
mRNA metabolic process	1
catalytic activity	1
cation binding	1
binding	1

Protein interactions and networks

STRING

280 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
APOBEC4	APOBEC1	P41238	964
APOBEC4	APOBEC2	Q9Y235	923
APOBEC4	AICDA	Q9GZX7	874
APOBEC4	CDA	P32320	848
APOBEC4	APOBEC3H	Q6NTF7	838
APOBEC4	APOBEC3D	Q96AK3	819
APOBEC4	APOBEC3F	Q8IUX4	815
APOBEC4	APOBEC3C	Q9NRW3	809
APOBEC4	APOBEC3A	P31941	800
APOBEC4	APOBEC3G	Q9HC16	788
APOBEC4	APOBEC3B	Q9UH17	746
APOBEC4	APOB	P04114	687
APOBEC4	A1CF	Q9NQ94	560
APOBEC4	ADAT2	Q7Z6V5	499
APOBEC4	CUL5	Q93034	459

IntAct

7 interactions, top by confidence:

A	B	Type	Score
APOBEC4	CASP6	psi-mi:“MI:0915”(physical association)	0.560
APOBEC4	RAN	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (3): APOBEC4 (Biochemical Activity), APOBEC4 (Two-hybrid), APOBEC4 (Two-hybrid)

ESM2 similar proteins: A0A140H546, A0A193AUK9, A0A482PJF5, A0A482PJY4, A0A482PUS2, A0JP89, A8WWR3, B3M1F2, B3P4M4, B4GZ07, B4HJA7, B4JSL2, B4KCG1, B4M686, B4N8G7, B4PVI7, B4QVV3, O13826, O42947, O60291, P23801, P32512, P38239, P75409, P90859, Q1L8G6, Q29B72, Q5XIQ4, Q621J7, Q69U49, Q6GMD3, Q6ZPS6, Q75CC8, Q7TNB8, Q7ZUL9, Q8J0M4, Q8LBA0, Q8RXD3, Q8WW27, Q8XAN6

Diamond homologs: Q497M3, Q6AXX9, Q8WP22, Q8WW27

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	45
Likely benign	4
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

225 predictions. Top by Δscore:

Variant	Effect	Δscore
1:183646802:TG:T	donor_gain	0.9800
1:183653067:ATTAC:A	donor_loss	0.9800
1:183653068:TTACC:T	donor_loss	0.9800
1:183653069:TA:T	donor_loss	0.9800
1:183653071:CCAT:C	donor_gain	0.9700
1:183653070:A:AC	donor_gain	0.9600
1:183653071:C:CC	donor_gain	0.9600
1:183648809:AACCT:A	acceptor_gain	0.9400
1:183648810:ACCTA:A	acceptor_gain	0.9400
1:183653066:AATT:A	donor_loss	0.9400
1:183648811:CCT:C	acceptor_gain	0.9200
1:183646803:GA:G	donor_gain	0.9100
1:183646804:AA:A	donor_gain	0.9100
1:183648810:ACC:A	acceptor_loss	0.9000
1:183648812:C:A	acceptor_gain	0.9000
1:183648813:T:A	acceptor_gain	0.8800
1:183652300:CATCA:C	donor_gain	0.8200
1:183648817:C:CT	acceptor_loss	0.7800
1:183648810:AC:A	acceptor_gain	0.7700
1:183648811:CC:C	acceptor_gain	0.7700
1:183652229:C:CA	donor_gain	0.7500
1:183653070:AC:A	donor_gain	0.7400
1:183653071:CC:C	donor_gain	0.7400
1:183653129:T:TA	donor_gain	0.7400
1:183653070:ACCAT:A	donor_gain	0.7300
1:183653071:CCATC:C	donor_gain	0.7300
1:183653102:T:A	donor_gain	0.7200
1:183653199:T:C	donor_gain	0.7200
1:183648814:A:C	acceptor_loss	0.7100
1:183648809:AAC:A	acceptor_gain	0.7000

AlphaMissense

2444 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:183648320:A:C	F154L	0.983
1:183648320:A:T	F154L	0.983
1:183648322:A:G	F154L	0.983
1:183648626:A:C	F52L	0.979
1:183648626:A:T	F52L	0.979
1:183648628:A:G	F52L	0.979
1:183648179:A:C	F201L	0.977
1:183648179:A:T	F201L	0.977
1:183648181:A:G	F201L	0.977
1:183648485:A:C	F99L	0.977
1:183648485:A:T	F99L	0.977
1:183648487:A:G	F99L	0.977
1:183648570:A:G	L71P	0.975
1:183648538:C:G	G82R	0.974
1:183648421:A:C	Y121D	0.972
1:183648321:A:G	F154S	0.966
1:183648405:G:C	P126R	0.966
1:183648620:G:C	F54L	0.966
1:183648620:G:T	F54L	0.966
1:183648622:A:G	F54L	0.966
1:183648579:A:G	F68S	0.965
1:183648537:C:T	G82D	0.964
1:183648675:C:G	R36P	0.963
1:183648212:A:C	S190R	0.962
1:183648212:A:T	S190R	0.962
1:183648214:T:G	S190R	0.962
1:183648405:G:T	P126H	0.962
1:183648532:C:G	A84P	0.962
1:183648531:G:T	A84D	0.961
1:183648638:A:C	F48L	0.961

dbSNP variants (sampled 300 via entrez): RS1000075133 (1:183655140 T>C), RS1000533964 (1:183655061 T>C), RS1000564961 (1:183651418 T>G), RS1001511566 (1:183649858 T>C), RS1001634475 (1:183652200 T>G), RS1001685028 (1:183651873 T>G), RS1002607715 (1:183651600 T>A,C), RS1003303563 (1:183653723 C>T), RS1003356024 (1:183653391 A>C,G), RS1003581823 (1:183646667 A>G), RS1003768543 (1:183646360 T>C), RS1003937570 (1:183647082 G>A), RS1005258553 (1:183653733 C>A), RS1005475533 (1:183647197 G>T), RS1005579482 (1:183652451 G>A)

Disease associations

OMIM: gene MIM:609908 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001795_9	Systemic lupus erythematosus	6.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
pirinixic acid	affects binding, increases activity, increases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Rotenone	decreases expression	1
Smoke	increases expression, increases abundance	1
Tobacco Smoke Pollution	decreases expression	1

Clinical trials (associated diseases)

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