APOBEC3A

protein-coding

apolipoprotein B mRNA editing enzyme catalytic subunit 3A, the group of Apolipoprotein B mRNA editing enzyme catalytic subunits

Gene summary

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. The protein encoded by this gene lacks the zinc binding activity of other family members. The protein plays a role in immunity, by restricting transmission of foreign DNA such as viruses. One mechanism of foreign DNA restriction is deamination of foreign double-stranded DNA cytidines to uridines, which leads to DNA degradation. However, other mechanisms are also thought to be involved, as anti-viral effect is not dependent on deaminase activity. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2012]

MANE transcript

NM_145699.4

Inheritance

—

ClinVar variants

U:22B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.59

Max pathogenic AF

—

Genomic locus

chr22:38,952,741-38,963,184

External References & Databases

Ensembl (ENSG00000128383)

Transcript & Mutation Effects

hg38 • Region Span ~10.4 kb

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GenCC 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 APOBEC3A variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 24

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_145699.4. 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 clinvar		1
missense			22 clinvar	2 clinvar		24
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	22	3	0	25

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_145699.4	RefSeq	NP_663745.1	5	MANE Select
ENST00000249116.7	Ensembl	ENSP00000249116.2	5	MANE Select
NM_001270406.2	RefSeq	NP_001257335.1	5	Standard
ENST00000402255.5	Ensembl	ENSP00000384359.1	5	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
clearance of foreign intracellular DNA by conversion of DNA cytidine to uridine
negative regulation of viral genome replication

Molecular Function

RNA binding
cytidine deaminase activity
protein binding
zinc ion binding
deoxycytidine deaminase activity

Cellular Component

nucleus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000402255
Coding exons: 5
Length: 10443
Individuals with no LoFs: 125702
Homozygous LoFs: 5
Heterozygous LoFs: 41
Defined: 125748
p: 0.000183

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.363	132	121	1.09	0.00000735	1310
Missense (PolyPhen)		29	34.466	0.84142		461
Synonymous	0.0764	48	48.7	0.986	0.00000319	363
Loss of Function	1.20	6	10.1	0.592	4.33e-7	110

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00041	0.00031	rare
Latino/Admixed American	0.000030	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00027	0.00027	rare
Finnish	0.000053	0.000046	rare
European (Non-Finnish)	0.00013	0.000088	rare
South Asian	0.00089	0.00078	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: DNA deaminase (cytidine deaminase) with restriction activity against viruses, foreign DNA and mobility of retrotransposons. Exhibits antiviral activity against adeno- associated virus (AAV) and human T-cell leukemia virus type 1 (HTLV-1) and may inhibit the mobility of LTR and non-LTR retrotransposons. Selectively targets single-stranded DNA and can deaminate both methylcytosine and cytosine in foreign DNA. Can induce somatic hypermutation in the nuclear and mitochondrial DNA. May also play a role in the epigenetic regulation of gene expression through the process of active DNA demethylation. {ECO:0000269|PubMed:10469298, ECO:0000269|PubMed:12859895, ECO:0000269|PubMed:16527742, ECO:0000269|PubMed:19461882, ECO:0000269|PubMed:20062055, ECO:0000269|PubMed:20615867, ECO:0000269|PubMed:21123384, ECO:0000269|PubMed:21368204, ECO:0000269|PubMed:21460793, ECO:0000269|PubMed:21496894, ECO:0000269|PubMed:22457529, ECO:0000269|PubMed:22896697}.;

Intolerance Scores

RVIS EVS: 0.37
RVIS percentile EVS: 75.12

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.749

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium