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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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APOBEC3H
apolipoprotein B mRNA editing enzyme catalytic subunit 3H
Chromosome 22 · 22q13.1
NCBI Gene: 164668Ensembl: ENSG00000100298.16HGNC: HGNC:24100UniProt: A0A087WZI3
90PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
nucleusnucleoplasmcytosolcytidine deaminase activityneurodegenerative diseasemultiple myelomaimmune deficiency, familial variableAutosomal recessive hyper-IgE syndrome
✦AI Summary

APOBEC3H (A3H) is a single-stranded DNA cytidine deaminase that functions as a potent restriction factor against HIV-1 and other retroviruses 1. The protein exhibits significant genetic diversity, with seven haplotypes (I-VII) present in human populations, of which haplotype II shows the strongest antiviral activity 23. A3H restricts viral replication through both deaminase-dependent and -independent mechanisms. The deaminase-dependent pathway involves converting cytidine to uridine in single-stranded viral DNA during reverse transcription, leading to G-to-A hypermutations that impair viral fitness 1. Additionally, A3H can inhibit HIV-1 DNA synthesis through deaminase-independent mechanisms 1. The protein's antiviral activity is closely linked to its subcellular localization, with haplotype II being predominantly cytoplasmic while haplotype I localizes to the nucleus 3. A3H function requires RNA-mediated dimerization, and the protein remains bound to cellular RNA even during ssDNA interactions 4. Unlike other APOBEC3 proteins, A3H haplotype II is resistant to HIV-1 Vif-mediated degradation, making it a particularly effective restriction factor 25. The protein demonstrates processivity on single-stranded DNA through sliding, jumping, and intersegmental transfer mechanisms 6.

Sources cited
1
A3H is a single-stranded DNA cytidine deaminase that restricts HIV-1 through deaminase-dependent and -independent mechanisms
PMID: 25614027
2
A3H has seven haplotypes with haplotype II showing strongest antiviral activity and resistance to HIV-1 Vif
PMID: 18945781
3
Haplotype II localizes predominantly to cytoplasm while haplotype I is nuclear, correlating with antiviral activity
PMID: 21653666
4
A3H function requires RNA-mediated dimerization and the protein remains bound to cellular RNA during DNA interactions
PMID: 30414963
5
A3H is one of four APOBEC3 proteins that potently restrict Vif-deficient HIV-1 in T cells
PMID: 21835787
6
A3H demonstrates processivity on single-stranded DNA through sliding, jumping, and intersegmental transfer mechanisms
PMID: 26396192
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.29Weak
multiple myelomaOpen Targets
0.16Weak
immune deficiency, familial variableOpen Targets
0.08Suggestive
Autosomal recessive hyper-IgE syndromeOpen Targets
0.07Suggestive
Autosomal recessive hyper-IgE syndrome due to TYK2 deficiencyOpen Targets
0.07Suggestive
immunodeficiency 35Open Targets
0.07Suggestive
Chronic mucocutaneous candidosisOpen Targets
0.07Suggestive
hyper-IgM syndrome type 2Open Targets
0.07Suggestive
immunodeficiency 86Open Targets
0.07Suggestive
isolated agammaglobulinemiaOpen Targets
0.07Suggestive
agammaglobulinemia 8, autosomal dominantOpen Targets
0.06Suggestive
immunodeficiency, common variable, 4Open Targets
0.06Suggestive
hyper-IgM syndrome type 3Open Targets
0.06Suggestive
immunodeficiency, common variable, 15Open Targets
0.06Suggestive
severe combined immunodeficiency due to CARD11 deficiencyOpen Targets
0.06Suggestive
IgAD1Open Targets
0.06Suggestive
X-linked agammaglobulinemiaOpen Targets
0.06Suggestive
hyper-IgM syndrome type 5Open Targets
0.06Suggestive
immunodeficiency, common variable, 7Open Targets
0.06Suggestive
severe combined immunodeficiency due to CORO1A deficiencyOpen Targets
0.06Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
COX7CProtein interaction100%UQCR10Protein interaction100%UQCRFS1Protein interaction100%CYC1Protein interaction100%UQCRBProtein interaction100%UQCRQProtein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
50%
Brain
24%
Ovary
17%
Liver
11%
Heart
3%
Gene Interaction Network
Click a node to explore
APOBEC3HCOX7CUQCR10UQCRFS1CYC1UQCRBUQCRQ
PROTEIN STRUCTURE
Preparing viewer…
PDB5W45 · 2.49 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.65LoF Tolerant
pLIⓘ
0.63Intermediate
Observed/Expected LoF0.36 [0.21–0.65]
RankingsWhere APOBEC3H stands among ~20K protein-coding genes
  • #5,286of 20,598
    Most Researched90
  • #4,727of 17,882
    Most Constrained (LOEUF)0.65
Genes detectedAPOBEC3H
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Natural Polymorphisms and Oligomerization of Human APOBEC3H Contribute to Single-stranded DNA Scanning Ability.
PMID: 26396192
J Biol Chem · 2015
1.00
2
Polymorphisms in Human APOBEC3H Differentially Regulate Ubiquitination and Antiviral Activity.
PMID: 32235597
Viruses · 2020
0.90
3
Sequence and structural determinants of human APOBEC3H deaminase and anti-HIV-1 activities.
PMID: 25614027
Retrovirology · 2015
0.80
4
Polymorphism in human APOBEC3H affects a phenotype dominant for subcellular localization and antiviral activity.
PMID: 21653666
J Virol · 2011
0.70
5
The Structural Interface between HIV-1 Vif and Human APOBEC3H.
PMID: 28031368
J Virol · 2017
0.60