APOBEC3C

Summary

APOBEC3C (apolipoprotein B mRNA editing enzyme catalytic subunit 3C, HGNC:17353) is a protein-coding gene on chromosome 22q13.1, encoding DNA dC->dU-editing enzyme APOBEC-3C (Q9NRW3). 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.

Source: NCBI Gene 27350 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 32 total
• Druggable target: yes
• MANE Select transcript: NM_014508

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17353
Approved symbol	APOBEC3C
Name	apolipoprotein B mRNA editing enzyme catalytic subunit 3C
Location	22q13.1
Locus type	gene with protein product
Status	Approved
Aliases	APOBEC1L, PBI, bK150C2.3, ARDC2, ARDC4, ARP5
Ensembl gene	ENSG00000244509
Ensembl biotype	protein_coding
OMIM	607750
Entrez	27350

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 nonsense_mediated_decay

ENST00000361441, ENST00000428892, ENST00000869067

RefSeq mRNA: 1 — MANE Select: NM_014508 NM_014508

CCDS: CCDS13983

Canonical transcript exons

ENST00000361441 — 4 exons

Exon	Start	End
ENSE00001725131	39015595	39015751
ENSE00001812045	39014257	39014379
ENSE00001863910	39018269	39020352
ENSE00003575577	39017766	39018045

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 94.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 46.7922 / max 1238.3851, expressed in 1683 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
192295	36.6477	1676
192296	10.1445	1426

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
leukocyte	CL:0000738	94.86	gold quality
granulocyte	CL:0000094	94.79	gold quality
monocyte	CL:0000576	94.78	gold quality
mononuclear cell	CL:0000842	94.74	gold quality
lymph node	UBERON:0000029	93.53	gold quality
right adrenal gland cortex	UBERON:0035827	93.40	gold quality
right adrenal gland	UBERON:0001233	93.20	gold quality
left adrenal gland	UBERON:0001234	91.94	gold quality
left adrenal gland cortex	UBERON:0035825	91.75	gold quality
adrenal cortex	UBERON:0001235	91.42	gold quality
rectum	UBERON:0001052	91.41	gold quality
stromal cell of endometrium	CL:0002255	91.12	gold quality
smooth muscle tissue	UBERON:0001135	90.80	gold quality
adrenal gland	UBERON:0002369	90.79	gold quality
parotid gland	UBERON:0001831	90.58	silver quality
bone marrow cell	CL:0002092	90.32	gold quality
blood	UBERON:0000178	89.95	gold quality
pancreatic ductal cell	CL:0002079	89.72	gold quality
spleen	UBERON:0002106	89.41	gold quality
gall bladder	UBERON:0002110	88.16	gold quality
right testis	UBERON:0004534	88.05	gold quality
buccal mucosa cell	CL:0002336	87.98	gold quality
tongue squamous epithelium	UBERON:0006919	87.87	silver quality
bone marrow	UBERON:0002371	87.71	gold quality
right ovary	UBERON:0002118	87.40	gold quality
trabecular bone tissue	UBERON:0002483	87.32	gold quality
olfactory bulb	UBERON:0002264	87.29	silver quality
left ovary	UBERON:0002119	87.27	gold quality
vermiform appendix	UBERON:0001154	87.13	gold quality
body of uterus	UBERON:0009853	87.13	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-8205	yes	352.15
E-MTAB-5061	yes	26.60
E-MTAB-9388	yes	8.36
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TET1

miRNA regulators (miRDB)

33 targeting APOBEC3C, 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-4283	100.00	66.42	2097
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-1255A	99.74	68.09	744
HSA-MIR-1255B-5P	99.74	68.16	741
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-7114-5P	98.51	67.87	1349
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-5589-5P	98.34	64.82	1148
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-637	97.91	64.05	1517
HSA-MIR-939-5P	97.10	65.80	1579
HSA-MIR-3674	97.01	68.86	1171
HSA-MIR-134-3P	96.83	66.22	1001
HSA-MIR-1343-5P	96.48	66.06	1506

Literature-anchored findings (GeneRIF, showing 40)

• different APOBEC3 family members function to neutralize specific lentiviruses (PMID:15466872)
• APOBEC3 proteins may help prevent the zoonotic infection of humans by simple retroviruses and provide a mechanism for how simple retroviruses can avoid inhibition by APOBEC3 family members. (PMID:15956565)
• evidence for a role of host-encoded APOBEC3 proteins in the regulation of L1 retrotransposition (PMID:16735504)
• reviews the current knowledge on the mechanism of APOBEC3-dependent retrovirus restriction and discuss whether this innate host-defense system actively contributes to HIV genetic variation (PMID:17078485)
• Differences in promiscuity of monocytes, macrophages, and DCs can be defined, at least partly, by disparities in APOBEC expression, with implications for enhancing cellular defenses against HIV-1. (PMID:17371941)
• The catalytic domain of APOBEC3 proteins may be important for proper folding and target factors such as RNA or protein interaction in addition to cytidine deamination. (PMID:17582006)
• These findings demonstrate that HBV is highly vulnerable to the editing activity of an endogenous human deaminase and suggest that A3C could contribute to innate anti-HBV host responses. (PMID:17625792)
• APOBEC3 suppresses HBV replication in hepatocytes by inhibiting hnRNP K-mediated transcription and expression of HBV genes as well as HBV core DNA synthesis. (PMID:17672864)
• study demonstrate that APOBEC3C is necessary and sufficient for G-to-A mutations in some HIV-1 strains (PMID:17967058)
• Stress causes APOBEC3A, APOBEC3B, APOBEC3C, and APOBEC3F to colocalize efficiently with Vif(IIIB) and mRNA-PABP1 complexes in stress granules (PMID:17977970)
• Study compared the antiviral activities of human and murine Apobec3 (A3), and found that, HIV is able to resist human A3G but is sensitive to murine A3, whereas murine leukemia virus is relatively resistant to murine A3 but sensitive to human A3G. (PMID:18032489)
• Partially active Vif alleles resulting in incomplete neutralization of cytoplasmic APOBEC3 molecules are directly responsible for the generation of a highly diverse, yet G-to-A biased, proviral reservoir (PMID:18391217)
• Cul5-E3 ubiquitin ligase appears to be a common pathway hijacked by HIV-1 and SIV Vif to defeat APOBEC3 proteins. (PMID:18419775)
• These results indicate that APOBEC3G, APOBEC3C and APOBEC3H have the ability to edit HBV DNA and that each protein is likely to contribute to various degrees to the generation of modified genomes in human liver cells. (PMID:18420796)
• Human APOBEC3 proteins inhibit porcine endogenous retrovirus replication, which may reduce risk for infection of human cells as a consequence of pig-to-human xenotransplantation. (PMID:18555089)
• IAPE and HERV-K elements are restricted at the entry, amplification and integration into their target genomes by the host APOBEC3 proteins. (PMID:18702815)
• Distinct determinants in HIV-1 Vif and human APOBEC3 proteins are required for the suppression of diverse host anti-viral proteins. (PMID:19088851)
• Major cellular components of human BRB could be primary cultured in vitro and different expression of APOBEC3 in human blood-retinal barrier was examined. (PMID:19369234)
• APOBEC3 roles in limiting viruse pathogenicity by partially restricting infection (PMID:19390611)
• The structure of APOBEC3C (A3C), a single-domain A3 with strong antilentiviral activity, was modeled. (PMID:19581596)
• 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 basic biology of the interactions between human APOBEC3 proteins and HIV-1 Vif, is reviewed. (PMID:20096141)
• Somatic hypermutation of human mitochondrial and nuclear DNA by APOBEC3 cytidine deaminases, a pathway for DNA catabolism. (PMID:21368204)
• The authors identified a single cysteine at position 320 (C320) that disrupts A3DE activity. (PMID:21430060)
• The result suggest that Core-A3C may be a candidate as a novel antiviral agent against human HBV infection. (PMID:21746770)
• Findings suggest that APOBEC3-mediated editing of HIV-1 could be modulated by host and virus genetic characteristics in the context of pediatric infection. (PMID:22145963)
• 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)
• a high-resolution crystal structure of APOBEC3C with the HIV-1 viral infectivity factor (Vif)-interaction interface. (PMID:23001005)
• This study confirmed the association of the APOBEC3 deletion with breast cancer risk among women of European ancestry. (PMID:23715497)
• The mechanism of APOBEC3C (A3C)-mediated LINE-1 inhibition was found to be deaminase independent, required an intact dimerization site and the RNA-binding pocket mutation R122A abolished L1 restriction by A3C. (PMID:24101588)
• APOBEC3 deaminases upregulated by IFN-beta induce E2 hypermutation of HPV16 in cervical keratinocytes. (PMID:24227842)
• 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)
• High APOBEC3C is associated with the pathogenesis of primary effusion lymphoma. (PMID:25650088)
• These results suggest that functional potential of APOBEC3B and APOBEC3C involved in cancer mutagenesis is associated with estrogen receptor status. (PMID:26682542)
• our results suggest that APOBEC3C is in fact involved in protecting hosts from lentiviruses. (PMID:27732658)
• Antiviral functions of APOBEC3C against HIV-1 and APOBEC3C binding capacity (PMID:28315663)
• Data suggest that heat shock proteins, in particular Hsp90, stimulate APOBEC3-mediated DNA deamination activity toward hepatitis B viral DNA, suggesting a potential physiological role in mutagenesis/carcinogenesis and viral innate immunity; Hsp90 stimulates deamination activity of APOBEC3G, APOBEC3B, and APOBEC3C during co-expression in human liver HepG2 cells. (PMID:28637869)
• A3C-Ile188 is capable of inhibiting Vif-deficient HIV-1 replication in T cells (PMID:30558640)
• genetic variations in APOBEC3 genes may affect the efficiency of hepatitis b virus elimination in humans. (PMID:31400856)
• Loop 1 of APOBEC3C Regulates its Antiviral Activity against HIV-1. (PMID:33068636)

Cross-species orthologs

0 orthologs

Paralogs (9): APOBEC3H (ENSG00000100298), APOBEC1 (ENSG00000111701), AICDA (ENSG00000111732), APOBEC2 (ENSG00000124701), APOBEC3A (ENSG00000128383), APOBEC3F (ENSG00000128394), APOBEC3B (ENSG00000179750), APOBEC3G (ENSG00000239713), APOBEC3D (ENSG00000243811)

Protein

Protein identifiers

DNA dC->dU-editing enzyme APOBEC-3C — Q9NRW3 (reviewed: Q9NRW3)

Alternative names: APOBEC1-like, Phorbolin I

All UniProt accessions (2): F8WB92, Q9NRW3

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), herpes simplex virus 1 (HHV-1) and Epstein-Barr virus (EBV) and may inhibit the mobility of LTR and non-LTR retrotransposons. May also play a role in the epigenetic regulation of gene expression through the process of active DNA demethylation.

Subunit / interactions. Homodimer. Interacts with TRIB3. Interacts with AGO2. (Microbial infection) Interacts with human foamy virus protein Bet; this interaction does not induce APOBEC3C degradation but prevents its dimerization and incorporation into the virion by binding of Bet close to or within the APOBEC3C dimerization site. (Microbial infection) Interacts with HIV-1 Vif.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Expressed in spleen, testes, peripherical blood lymphocytes, heart, thymus, prostate and ovary.

Activity regulation. (Microbial infection) Antiviral activity is neutralized by the HIV-1 virion infectivity factor (Vif), that prevents its incorporation into progeny HIV-1 virions by both inhibiting its translation and/or by inducing its ubiquitination and subsequent degradation by the 26S proteasome.

Induction. 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.

Similarity. Belongs to the cytidine and deoxycytidylate deaminase family.

RefSeq proteins (1): NP_055323* (*=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 (35 total): mutagenesis site 13, helix 7, strand 5, binding site 3, turn 2, chain 1, domain 1, region of interest 1, sequence conflict 1, active site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3VOW	X-RAY DIFFRACTION	2.15
3VM8	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NRW3-F1	91.29	0.81

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): 68 (proton donor)

Ligand- & substrate-binding residues (3): 66; 97; 100

Mutagenesis-validated functional residues (13):

Position	Phenotype
79	resistant to hiv-1 vif and reduces vif binding.
80	resistant to hiv-1 vif and reduces vif binding.
81	resistant to hiv-1 vif and reduces vif binding.
86	resistant to hiv-1 vif and abolishes vif binding.
106	resistant to hiv-1 vif and reduces vif binding.
107	resistant to hiv-1 vif and abolishes vif binding.
109	resistant to hiv-1 vif.
111	resistant to hiv-1 vif and reduces vif binding.
129	no effect on vif binding.
141	remains sensitive to hiv-1 vif but abolishes vif binding.
72	resistant to hiv-1 vif and abolishes vif binding.
75	resistant to hiv-1 vif and reduces vif binding.
76	resistant to hiv-1 vif and reduces vif binding.

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: 126 (showing top): GOBP_NEGATIVE_REGULATION_OF_VIRAL_PROCESS, GOBP_DNA_MODIFICATION, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_RNA_MODIFICATION, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, GOBP_VIRAL_GENOME_REPLICATION, GOBP_VIRAL_LIFE_CYCLE, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GOBP_TRANSCRIPTION_INITIATION_AT_RNA_POLYMERASE_II_PROMOTER, GOBP_DEFENSE_RESPONSE_TO_VIRUS, MORF_PDPK1, GOBP_CHROMATIN_REMODELING, GOBP_REGULATION_OF_VIRAL_GENOME_REPLICATION, GOBP_NEGATIVE_REGULATION_OF_VIRAL_GENOME_REPLICATION, GOBP_EPIGENETIC_REGULATION_OF_GENE_EXPRESSION

GO Biological Process (12): 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), negative regulation of macromolecule biosynthetic process (GO:0010558), defense response to symbiont (GO:0140546)

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 (3): P-body (GO:0000932), 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
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
macromolecule biosynthetic process	1
negative regulation of biosynthetic process	1
regulation of macromolecule biosynthetic process	1
negative regulation of macromolecule metabolic process	1
defense response to other organism	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
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

966 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
APOBEC3C	CDA	P32320	865
APOBEC3C	CUL5	Q93034	853
APOBEC3C	APOB	P04114	816
APOBEC3C	APOBEC4	Q8WW27	809
APOBEC3C	UNG	P13051	537
APOBEC3C	ELOB	Q15370	508
APOBEC3C	APOBEC3H	Q6NTF7	496
APOBEC3C	RBX1	P62877	473
APOBEC3C	APOBEC3A	P31941	470
APOBEC3C	ELOC	Q15369	464
APOBEC3C	CBFB	Q13951	457
APOBEC3C	APOBEC3G	Q9HC16	456
APOBEC3C	TRIB3	Q96RU7	451
APOBEC3C	PPP2R5A	Q15172	447
APOBEC3C	NF1	P21359	444

IntAct

102 interactions, top by confidence:

A	B	Type	Score
XPC	CETN3	psi-mi:“MI:0914”(association)	0.730
RBMX	APOBEC3C	psi-mi:“MI:0915”(physical association)	0.720
APOBEC3C	RBMY1F	psi-mi:“MI:0915”(physical association)	0.720
APOBEC3C	RBMX	psi-mi:“MI:0915”(physical association)	0.720
RBMY1F	APOBEC3C	psi-mi:“MI:0915”(physical association)	0.720
ZNF48	APOBEC3C	psi-mi:“MI:0915”(physical association)	0.670
TRIB3	APOBEC3C	psi-mi:“MI:0915”(physical association)	0.670
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
APOBEC3C	RBMY1A1	psi-mi:“MI:0915”(physical association)	0.560
RBMY1A1	APOBEC3C	psi-mi:“MI:0915”(physical association)	0.560
HNRNPK	APOBEC3C	psi-mi:“MI:0915”(physical association)	0.560
ZNF408	APOBEC3C	psi-mi:“MI:0915”(physical association)	0.560
ZNF250	APOBEC3C	psi-mi:“MI:0915”(physical association)	0.560
APOBEC3C	ZNF581	psi-mi:“MI:0915”(physical association)	0.560
HHEX	APOBEC3C	psi-mi:“MI:0915”(physical association)	0.560
APOBEC3C	CHTOP	psi-mi:“MI:0915”(physical association)	0.560
PRR3	APOBEC3C	psi-mi:“MI:0915”(physical association)	0.560
RPL28	MAGEB2	psi-mi:“MI:0914”(association)	0.560
ZBTB48	ZBTB24	psi-mi:“MI:0914”(association)	0.530
APOBEC3C	SRPK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
gag	APOBEC3C	psi-mi:“MI:0915”(physical association)	0.400
APOBEC3C	APOBEC3C	psi-mi:“MI:0915”(physical association)	0.400
APOBEC3C	vif	psi-mi:“MI:0915”(physical association)	0.400
SDC1	ILVBL	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (212): APOBEC3C (Two-hybrid), APOBEC3C (Two-hybrid), RBMY1F (Two-hybrid), APOBEC3C (Affinity Capture-MS), APOBEC3C (Affinity Capture-MS), APOBEC3C (Affinity Capture-MS), APOBEC3C (Affinity Capture-MS), APOBEC3C (Affinity Capture-MS), APOBEC3C (Affinity Capture-MS), APOBEC3C (Affinity Capture-MS), APOBEC3C (Affinity Capture-MS), APOBEC3C (Biochemical Activity), APOBEC3C (Affinity Capture-MS), APOBEC3C (Affinity Capture-MS), APOBEC3C (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

1 interactions.

A	Effect	B	Mechanism
APOBEC3C	up-regulates	“Clearance_of_foreign intracellular_DNA”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 88 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
Response of EIF2AK4 (GCN2) to amino acid deficiency	7	12.5×	3e-04
Peptide chain elongation	6	12.3×	7e-04
Viral mRNA Translation	6	12.3×	7e-04
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	6	12.1×	7e-04
Selenocysteine synthesis	6	11.6×	7e-04
Eukaryotic Translation Termination	6	11.6×	7e-04
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	6	11.4×	7e-04
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	6	11.4×	7e-04

GO biological processes:

GO term	Partners	Fold	FDR
ribosomal small subunit biogenesis	5	14.4×	4e-03
cytoplasmic translation	6	14.1×	1e-03
translation	8	10.4×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

717 predictions. Top by Δscore:

Variant	Effect	Δscore
22:39018366:GC:G	donor_gain	1.0000
22:39018374:A:T	donor_gain	1.0000
22:39018362:G:GT	donor_gain	0.9900
22:39018383:A:AG	donor_gain	0.9900
22:39018384:G:GG	donor_gain	0.9900
22:39014375:ATCAG:A	donor_loss	0.9800
22:39014376:TCAG:T	donor_loss	0.9800
22:39014377:CAG:C	donor_loss	0.9800
22:39014378:AGGTA:A	donor_loss	0.9800
22:39014379:GG:G	donor_loss	0.9800
22:39014380:G:GA	donor_loss	0.9800
22:39014381:T:A	donor_loss	0.9800
22:39018044:AGG:A	donor_loss	0.9800
22:39018047:T:G	donor_loss	0.9800
22:39014779:G:GG	donor_gain	0.9700
22:39015589:CTTCA:C	acceptor_loss	0.9700
22:39015591:TCAG:T	acceptor_loss	0.9700
22:39015592:CA:C	acceptor_loss	0.9700
22:39015593:A:AG	acceptor_gain	0.9700
22:39015593:AG:A	acceptor_loss	0.9700
22:39015593:AGA:A	acceptor_loss	0.9700
22:39015594:G:A	acceptor_loss	0.9700
22:39015594:G:C	acceptor_loss	0.9700
22:39015594:G:GG	acceptor_gain	0.9700
22:39015696:A:T	donor_gain	0.9700
22:39017971:A:AG	acceptor_gain	0.9700
22:39017972:G:GG	acceptor_gain	0.9700
22:39014299:G:GT	donor_gain	0.9600
22:39015594:GAA:G	acceptor_gain	0.9600
22:39018372:G:GT	donor_gain	0.9600

AlphaMissense

1268 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:39015638:T:C	F21L	0.966
22:39015640:T:A	F21L	0.966
22:39015640:T:G	F21L	0.966
22:39017910:T:C	F107L	0.965
22:39017912:C:A	F107L	0.965
22:39017912:C:G	F107L	0.965
22:39015686:T:C	F37L	0.964
22:39015688:C:A	F37L	0.964
22:39015688:C:G	F37L	0.964
22:39017874:A:C	S95R	0.960
22:39017876:C:A	S95R	0.960
22:39017876:C:G	S95R	0.960
22:39015626:T:C	F17L	0.957
22:39015628:C:A	F17L	0.957
22:39015628:C:G	F17L	0.957
22:39015740:T:C	F55L	0.952
22:39015742:C:A	F55L	0.952
22:39015742:C:G	F55L	0.952
22:39018292:T:C	F160L	0.950
22:39018294:T:A	F160L	0.950
22:39018294:T:G	F160L	0.950
22:39017802:T:C	F71L	0.949
22:39017804:C:A	F71L	0.949
22:39017804:C:G	F71L	0.949
22:39018271:T:C	F153L	0.948
22:39018273:T:A	F153L	0.948
22:39018273:T:G	F153L	0.948
22:39017859:T:A	W90R	0.929
22:39017859:T:C	W90R	0.929
22:39018316:T:C	F168L	0.925

dbSNP variants (sampled 300 via entrez): RS1000330400 (22:39014557 C>G), RS1000641205 (22:39013973 A>C), RS1001663786 (22:39016800 C>A), RS1001704637 (22:39012543 A>T), RS1001800557 (22:39020822 C>G), RS1001946306 (22:39015329 A>G), RS1002431587 (22:39013504 A>G), RS1002584405 (22:39020351 C>A,T), RS1003003154 (22:39020106 G>C), RS1003013699 (22:39012568 T>C), RS1003153705 (22:39012779 C>T), RS1003347991 (22:39013523 G>A), RS1003445930 (22:39013760 C>A,T), RS1003848518 (22:39017752 T>G), RS1003901984 (22:39012818 A>G)

Disease associations

OMIM: gene MIM:607750 | 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
GCST002408_17	Response to methotrexate in juvenile idiopathic arthritis	9.000000e-08
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): CHEMBL5724743 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression	4
(+)-JQ1 compound	decreases expression	3
sodium arsenite	affects expression, decreases expression	2
Acetaminophen	decreases expression, increases expression	2
Fluorouracil	affects response to substance, decreases expression, increases expression	2
Tobacco Smoke Pollution	decreases expression	2
aristolochic acid I	increases expression	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
potassium perchlorate	increases expression	1
titanium dioxide	increases expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
1-nitropyrene	decreases expression	1
avobenzone	increases expression	1
di-n-butylphosphoric acid	affects expression	1
nutlin 3	affects cotreatment, increases secretion	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Artesunate	increases phosphorylation, increases reaction, increases response to substance, increases expression	1
Air Pollutants	decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dactinomycin	affects cotreatment, increases secretion	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Demecolcine	increases expression	1
Diuron	decreases expression	1
Doxorubicin	affects response to substance	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5650918	Binding	Binding affinity to human APOBEC3C incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SC95	HAP1 APOBEC3C (-) 1	Cancer cell line	Male
CVCL_SC96	HAP1 APOBEC3C (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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