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): 55 total
• GTEx eGene: eQTL in 2 tissues, sQTL in 0 (q < 0.05)
• Constraint (gnomAD): pLI 0.52 (intermediate), LOEUF 1.41 (unconstrained)
• MANE Select transcript: NM_203454
• Notable: 55 clinical variants but no curated precision-oncology (CIViC) evidence yet

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

MANE Select: ENST00000308641

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 3: 1

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.

Highest expression (Bgee): bronchial epithelial cell, olfactory segment of nasal mucosa, bronchus, mucosa of paranasal sinus, sperm.

Genetic regulation across tissues (GTEx eQTL / sQTL)

APOBEC4 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 2 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

2 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	2.3e-08	-0.29	1:183650298:C:T
Lung	eqtl	4.6e-02	-0.19	1:183641554:GC:G

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

showing 100 of 200 tissues 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
vastus lateralis	UBERON:0001379	41.41	gold quality
quadriceps femoris	UBERON:0001377	41.37	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
duodenum	UBERON:0002114	41.15	silver quality
upper leg skin	UBERON:0004262	41.13	silver quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
amniotic fluid	UBERON:0000173	40.69	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
biceps brachii	UBERON:0001507	40.57	gold quality
myocardium	UBERON:0002349	40.45	gold quality
gingival epithelium	UBERON:0001949	40.43	gold quality
germinal epithelium of ovary	UBERON:0001304	40.33	gold quality
mammary duct	UBERON:0001765	40.32	gold quality
esophagus squamous epithelium	UBERON:0006920	40.29	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	40.27	gold quality
jejunum	UBERON:0002115	40.18	gold quality
cartilage tissue	UBERON:0002418	40.06	gold quality
mucosa of sigmoid colon	UBERON:0004993	39.95	gold quality
bone marrow	UBERON:0002371	39.87	gold quality
colonic mucosa	UBERON:0000317	39.86	gold quality
cortical plate	UBERON:0005343	39.86	gold quality
deltoid	UBERON:0001476	39.83	gold quality
saphenous vein	UBERON:0007318	39.83	gold quality
parotid gland	UBERON:0001831	39.81	gold quality
oocyte	CL:0000023	39.80	gold quality
urethra	UBERON:0000057	39.80	gold quality
heart right ventricle	UBERON:0002080	39.79	gold quality
pericardium	UBERON:0002407	39.77	gold quality
layer of synovial tissue	UBERON:0007616	39.77	gold quality
endothelial cell	CL:0000115	39.75	gold quality
synovial joint	UBERON:0002217	39.70	gold quality
dorsal root ganglion	UBERON:0000044	39.68	gold quality
nipple	UBERON:0002030	39.68	gold quality
decidua	UBERON:0002450	39.65	gold quality
penis	UBERON:0000989	39.64	gold quality
gingiva	UBERON:0001828	39.64	gold quality
trigeminal ganglion	UBERON:0001675	39.63	gold quality
tendon of biceps brachii	UBERON:0008188	39.60	gold quality
inferior vagus X ganglion	UBERON:0005363	39.57	gold quality
superior surface of tongue	UBERON:0007371	39.56	gold quality
pylorus	UBERON:0001166	39.55	gold quality
renal medulla	UBERON:0000362	39.53	gold quality
pons	UBERON:0000988	39.51	gold quality
thymus	UBERON:0002370	39.50	gold quality
medulla oblongata	UBERON:0001896	39.48	gold quality
superior vestibular nucleus	UBERON:0007227	39.47	gold quality
cardia of stomach	UBERON:0001162	39.46	gold quality
parietal pleura	UBERON:0002400	39.45	gold quality
Brodmann (1909) area 23	UBERON:0013554	39.40	gold quality
dorsal plus ventral thalamus	UBERON:0001897	39.38	gold quality
tongue	UBERON:0001723	39.37	gold quality
cerebellar vermis	UBERON:0004720	39.37	gold quality
oral cavity	UBERON:0000167	39.35	gold quality
subthalamic nucleus	UBERON:0001906	39.35	gold quality
ventral tegmental area	UBERON:0002691	39.35	gold quality
trachea	UBERON:0003126	39.33	gold quality
parietal lobe	UBERON:0001872	39.32	gold quality
vena cava	UBERON:0004087	39.31	gold quality
pharyngeal mucosa	UBERON:0000355	39.27	gold quality
substantia nigra pars compacta	UBERON:0001965	39.23	gold quality
visceral pleura	UBERON:0002401	39.23	gold quality
postcentral gyrus	UBERON:0002581	39.23	gold quality
body of tongue	UBERON:0011876	39.22	gold quality
medial globus pallidus	UBERON:0002477	39.18	gold quality
trabecular bone tissue	UBERON:0002483	39.18	gold quality
globus pallidus	UBERON:0001875	39.15	gold quality
substantia nigra pars reticulata	UBERON:0001966	39.11	gold quality
entorhinal cortex	UBERON:0002728	39.05	gold quality
lateral nuclear group of thalamus	UBERON:0002736	39.00	gold quality
corpus epididymis	UBERON:0004359	38.98	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

HPA expression

RNA tissue specificity: Group enriched

41 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Fallopian tube	tissue	10.9
Testis	tissue	9.3
Choroid plexus	tissue	4.6
Periaqueductal gray	tissue	4.1
Postcentral gyrus	tissue	3.5
Basal ganglia	tissue	3.2
Amygdala	tissue	2.7
Olfactory bulb	tissue	2.7
Hippocampus	tissue	2.6
Hippocampal formation	tissue	2.5
Cerebral cortex	tissue	2.4
Septum	tissue	2.4
Insular cortex	tissue	2.4
Retrosplenial and cingulate cortex	tissue	2.3
Ventral forebrain	tissue	2.2
Temporal cortex	tissue	2.2
Nucleus accumbens	tissue	2.1
Entorhinal cortex	tissue	2.1
Prefrontal cortex	tissue	2.0
Hypothalamus	tissue	2.0
Retrosplenial cortex	tissue	2.0
Occipital cortex	tissue	1.9
Cerebellum	tissue	1.8
Somatosensory cortex	tissue	1.7
Motor cortex	tissue	1.6
Putamen	tissue	1.5
Pons	tissue	1.4
Locus coeruleus	tissue	1.4
Midbrain	tissue	1.3
Thalamus	tissue	1.2
Medulla oblongata	tissue	1.1
Lung	tissue	1.1
Corpus callosum	tissue	0.9
Superior colliculi	tissue	0.8
Substantia nigra	tissue	0.7
Spinal cord	tissue	0.6
Endometrium 1	tissue	0.2
Cervix	tissue	0.1
Stomach 1	tissue	0.1
Small intestine	tissue	0.1
Duodenum	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 188; highest nTPM — Vermis (4.5), Flocculonodular lobe (4.1), Cerebellar cortex (4.0), Inferior parietal lobule (3.6), Posterior cingulate cortex (3.6).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting APOBEC4 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 100 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 0.522, LOEUF 1.41, missense Z 1.55 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000308641 — one region, missense o/e 0.85.

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

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Macaca fascicularis	Q8WP22	92.4%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
ARPC5	protein-coding	10092
TSEN15	protein-coding	116461
COLGALT2	protein-coding	23127
RGL1	protein-coding	23179
SMG7-AS1	ncRNA	284649
NCF2	protein-coding	4688
SMG7	protein-coding	9887

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: PF18775

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

Structure

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Metabolic proteins, Predicted intracellular proteins

Protein evidence: Evidence at protein level

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)

Position	Role
95	proton donor

Ligand- & substrate-binding residues (3)

Position	Role
93	Zn(2+)
127	Zn(2+)
134	Zn(2+)

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 4; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

4 pathways:

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

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)

Reactome top-level categories

3 top-level categories:

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

GO top-level categories

5 GO namespaces:

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

Protein interactions and networks

STRING

showing 15 of 242 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
APOBEC4	APOBEC1	P41238	966
APOBEC4	APOBEC2	Q9Y235	923
APOBEC4	AICDA	Q9GZX7	878
APOBEC4	CDA	P32320	837
APOBEC4	APOBEC3H	Q6NTF7	801
APOBEC4	APOBEC3D	Q96AK3	795
APOBEC4	APOBEC3F	Q8IUX4	793
APOBEC4	APOBEC3C	Q9NRW3	777
APOBEC4	APOBEC3A	P31941	773
APOBEC4	APOBEC3G	Q9HC16	756
APOBEC4	APOBEC3B	Q9UH17	749
APOBEC4	APOB	P04114	666
APOBEC4	A1CF	Q9NQ94	555
APOBEC4	ADAT2	Q7Z6V5	513
APOBEC4	CUL5	Q93034	465

IntAct

Human interaction partners of APOBEC4 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

2 partners by confidence:

Partner	Interaction type	MIscore	Records
CASP6	physical association	0.560	3
RAN	physical association	0.560	3

BioGRID (3 interactions; top human partners by supporting records): FBXO7 (Biochemical Activity), TRIM55 (Two-hybrid), TRIM63 (Two-hybrid)

Disease & clinical

Genetic variants

Variant evidence for APOBEC4: 55 ClinVar records (0 pathogenic / likely pathogenic); 1 GWAS association.

ClinVar

55 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	3

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 18 predictions of 93):

Position(s)	Effect	Δscore	Sites
1:183653070–183653071	donor_loss	0.9800	5
1:183653070	donor_loss	0.9700
1:183648812	acceptor_gain	0.9100
1:183648812–183648813	acceptor_loss	0.8900	5
1:183653069	donor_loss	0.8200
1:183648818	acceptor_loss	0.7300
1:183653199	donor_gain	0.7300
1:183653102	donor_gain	0.7200
1:183648814	acceptor_loss	0.7100
1:183653069	donor_loss	0.6800

AlphaMissense

527 missense substitutions predicted likely pathogenic (of 2,444 scored), across 143 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
F99	8	0.915	0.977
N170	8	0.893	0.959
F154	8	0.889	0.983
F52	8	0.880	0.979
D222	8	0.876	0.942
H34	8	0.862	0.955
F68	8	0.853	0.965
C87	7	0.893	0.950
F201	7	0.891	0.977
C127	7	0.885	0.957
C31	7	0.883	0.938
C134	7	0.868	0.949
W194	7	0.868	0.938
C28	7	0.857	0.939
H93	7	0.848	0.955
F141	7	0.846	0.952
F48	7	0.828	0.961
F54	7	0.828	0.966
E95	7	0.825	0.905
W21	7	0.806	0.938

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Uterine Corpus Endometrial Carcinoma)

Disease associations

OMIM: gene MIM:609908 | disease phenotypes:

GWAS associations

1 associations:

Study	Trait	p-value
GCST001795_9	Systemic lupus erythematosus	6e-6

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
pirinixic acid	increases activity, increases expression, affects binding	1
Air Pollutants	increases expression, increases abundance	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)

Via MONDO — disease-level, not drug-specific.