APOBEC3C

Chr 22

apolipoprotein B mRNA editing enzyme catalytic subunit 3C

NCBI Gene: 27350ENSG00000244509UniProt: Q9NRW3

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

50
ClinVar variants
16
Pathogenic / LP
0.03
pLI score
0
Active trials
Clinical Summary— APOBEC3C
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.03) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
16 Pathogenic / Likely Pathogenic· 30 VUS of 50 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.94LOEUF
pLI 0.027
Z-score 1.70
OE 0.41 (0.20–0.94)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.46Z-score
OE missense 1.12 (0.97–1.30)
128 obs / 114.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.41 (0.20–0.94)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.12 (0.97–1.30)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.18
0≤1.21.6
LoF obs/exp: 4 / 9.7Missense obs/exp: 128 / 114.3Syn Z: -0.92

ClinVar Variant Classifications

50 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15
Likely Pathogenic1
VUS30
Likely Benign1
Benign1
15
Pathogenic
1
Likely Pathogenic
30
VUS
1
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
15
0
15
Likely Pathogenic
0
0
1
0
1
VUS
0
27
3
0
30
Likely Benign
0
1
0
0
1
Benign
0
1
0
0
1
Total02919048

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

APOBEC3C · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
APOBEC3 upregulation drives gemcitabine resistance.
Maciejowski J et al.·Nat Cancer
2024
Different antiviral activities of natural APOBEC3C, APOBEC3G, and APOBEC3H variants against hepatitis B virus.
Kanagaraj A et al.·Biochem Biophys Res Commun
2019
Evaluation of APOBEC3 expression as prognostic marker in squamous cell carcinoma of the penis.
Trimmel B et al.·Sci Rep
2022
Expression patterns of LncRNA-GAS5 and its target APOBEC3C gene through miR-103 in breast cancer patients.
Kanabe BO et al.·Cell Mol Biol (Noisy-le-grand)
2021Cohort
A novel prognostic classification integrating lipid metabolism and immune co-related genes in acute myeloid leukemia.
Li D et al.·Front Immunol
2023
APOBEC3C is a novel target for the immune treatment of lower-grade gliomas.
Zhao S et al.·Neurol Res
2024
APOBEC3C coordinates DDX5 in R-loop resolution and dynamic control of Chk1-mediated stress-responsive circuitry as a prerequisite for gemcitabine resistance in p53-deficient cells.
Tao L et al.·Cell Death Dis
2026
Genome-wide association study of inhaled corticosteroid response in admixed children with asthma.
Hernandez-Pacheco N et al.·Clin Exp Allergy
2019Clinical trial
Natural APOBEC3C variants can elicit differential HIV-1 restriction activity.
Anderson BD et al.·Retrovirology
2018
The eQTL-missense polymorphisms of APOBEC3H are associated with lung cancer risk in a Han Chinese population.
Zhu M et al.·Sci Rep
2015
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools