APOBEC1

Chr 12

apolipoprotein B mRNA editing enzyme catalytic subunit 1

Also known as: APO1, APOBEC-1, BEDP, CDAR1, HEPR

This cytidine deaminase enzyme catalyzes C-to-U postranscriptional editing of mRNAs including apolipoprotein B and neurofibromatosis-1 transcripts, forming editing complexes with cofactor proteins. Biallelic mutations cause autosomal recessive developmental and epileptic encephalopathy with developmental delay, seizures, and brain malformations typically presenting in infancy. The gene is not constrained against loss-of-function variants.

Summary from RefSeq, UniProt
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0
Active trials
23
Pubs (1 yr)
0
P/LP submissions
P/LP missense
1.59
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryAPOBEC1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.59LOEUF
pLI 0.000
Z-score 0.03
OE 0.99 (0.631.59)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.77Z-score
OE missense 0.81 (0.690.95)
109 obs / 134.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.99 (0.631.59)
00.351.4
Missense OE0.81 (0.690.95)
00.61.4
Synonymous OE0.90
01.21.6
LoF obs/exp: 12 / 12.1Missense obs/exp: 109 / 134.2Syn Z: 0.54
DN
0.7035th %ile
GOF
0.6443th %ile
LOF
0.2484th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

APOBEC1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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