ABCA7

Chr 19AD

ATP binding cassette subfamily A member 7

Also known as: ABCA-SSN, ABCX, AD9

The ABCA7 protein is an ATP-binding cassette transporter that catalyzes phospholipid translocation across cell membranes and plays important roles in lipid homeostasis, macrophage-mediated phagocytosis, and clearance of amyloid-beta by microglial cells. Mutations cause autosomal dominant susceptibility to Alzheimer disease. The gene shows tolerance to loss-of-function variants (LOEUF 1.067), suggesting that complete loss of function may not be the primary disease mechanism in affected individuals.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismADLOEUF 1.071 OMIM phenotype
Clinical SummaryABCA7
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.07LOEUF
pLI 0.000
Z-score 0.97
OE 0.90 (0.751.07)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.47Z-score
OE missense 1.11 (1.061.16)
1516 obs / 1363.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.90 (0.751.07)
00.351.4
Missense OE1.11 (1.061.16)
00.61.4
Synonymous OE1.05
01.21.6
LoF obs/exp: 90 / 100.5Missense obs/exp: 1516 / 1363.2Syn Z: -1.07
DN
0.6259th %ile
GOF
0.72top 25%
LOF
0.3066th %ile

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

GOFprediction above median
DNprediction above median
LOF1 literature citation

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.

Literature Evidence

LOFIn a patient with late-onset Alzheimer disease-9 (AD9; 608907), Cuyvers et al. (2015) identified a heterozygous c.3641G-A transition (c.3641G-A, NM_019112.3) in exon 27 of the ABCA7 gene, resulting in a trp1214-to-ter (W1214X) substitution. The variant was not found in 757 controls. Patient brain tiPMID:26141617

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ABCA7 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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