APOBEC3H
protein-codingapolipoprotein B mRNA editing enzyme catalytic subunit 3H, the group of Apolipoprotein B mRNA editing enzyme catalytic subunits
Gene summary
This gene encodes a member of the apolipoprotein B mRNA-editing enzyme catalytic polypeptide 3 family of proteins. The encoded protein is a cytidine deaminase that has antiretroviral activity by generating lethal hypermutations in viral genomes. Polymorphisms and alternative splicing in this gene influence its antiretroviral activity and are associated with increased resistence to human immunodeficiency virus type 1 infection in certain populations. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Oct 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~6.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to APOBEC3H variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_181773.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | 2 | |||
| missense | 28 | 2 | 30 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 28 | 3 | 1 | 32 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_861438.3 | 4 | MANE Select | |
| Ensembl | ENSP00000411754.3 | 4 | MANE Select | |
| RefSeq | NP_001159474.2 | 4 | Standard | |
| RefSeq | NP_001159475.2 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Metabolism of RNA
- Formation of the Editosome
- mRNA Editing: C to U Conversion
- mRNA Editing
Biological Process
- cytidine deamination
- negative regulation of transposition
- cytidine to uridine editing
- innate immune response
- negative regulation of single stranded viral RNA replication via double stranded DNA intermediate
Molecular Function
- RNA binding
- cytidine deaminase activity
- protein binding
- zinc ion binding
Cellular Component
- P-body
- nucleus
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000401756
- Coding exons
- 4
- Length
- 6844
- Individuals with no LoFs
- 125540
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 206
- Defined
- 125747
- p
- 0.000823
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0191 | 127 | 128 | 0.995 | 0.00000820 | 1305 |
| Missense (PolyPhen) | 33 | 39.759 | 0.83001 | 456 | ||
| Synonymous | -0.634 | 58 | 52.2 | 1.11 | 0.00000347 | 370 |
| Loss of Function | 1.53 | 6 | 11.6 | 0.515 | 6.44e-7 | 125 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00031 | 0.00031 | rare |
| Latino/Admixed American | 0.00023 | 0.00023 | rare |
| Ashkenazi Jewish | 0.0016 | 0.0016 | notable |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0.0010 | 0.0010 | notable |
| European (Non-Finnish) | 0.0012 | 0.0012 | notable |
| South Asian | 0.00027 | 0.00026 | rare |
| Other | 0.00099 | 0.00081 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: DNA deaminase (cytidine deaminase) which acts as an inhibitor of retrovirus replication and retrotransposon mobility via deaminase-dependent and -independent mechanisms. The A3H- var/haplotype 2 exhibits antiviral activity against vif-deficient HIV-1. 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 also against T-cell leukemia virus type 1 (HTLV-1) and may inhibit the mobility of LTR and non-LTR retrotransposons. {ECO:0000269|PubMed:16571802, ECO:0000269|PubMed:16920826, ECO:0000269|PubMed:18299330, ECO:0000269|PubMed:18779051, ECO:0000269|PubMed:18827027, ECO:0000269|PubMed:20062055, ECO:0000269|PubMed:21835787, ECO:0000269|PubMed:22457529, ECO:0000269|PubMed:22915799, ECO:0000269|PubMed:23097438}.;
Recessive Scores
- pRec
- 0.119
Intolerance Scores
- LoFtool
- 0.871
- RVIS EVS
- 0.71
- RVIS percentile EVS
- 85.53
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0116
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |