ABCA2

Chr 9AR

ATP binding cassette subfamily A member 2

Also known as: ABC2, IDPOGSA

ABCA2 encodes an ATP-binding cassette transporter that regulates cholesterol homeostasis by modulating sphingolipid metabolism in late endosomes and lysosomes, and may play a role in myelin formation. Biallelic mutations cause autosomal recessive intellectual developmental disorder with poor growth and with or without seizures or ataxia. The gene is highly constrained against loss-of-function variants, indicating its critical importance for normal cellular function.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.171 OMIM phenotype
Clinical SummaryABCA2
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
10 unique Pathogenic / Likely Pathogenic· 203 VUS of 300 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.17LOEUF
pLI 1.000
Z-score 8.92
OE 0.10 (0.070.17)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
4.91Z-score
OE missense 0.65 (0.620.69)
1029 obs / 1578.1 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.10 (0.070.17)
00.351.4
Missense OE0.65 (0.620.69)
00.61.4
Synonymous OE1.16
01.21.6
LoF obs/exp: 12 / 115.3Missense obs/exp: 1029 / 1578.1Syn Z: -3.36

ClinVar Variant Classifications

300 submitted variants in ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic4
VUS203
Likely Benign23
Benign1
Conflicting2
6
Pathogenic
4
Likely Pathogenic
203
VUS
23
Likely Benign
1
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
4
0
6
Likely Pathogenic
3
0
1
0
4
VUS
0
200
3
0
203
Likely Benign
0
9
2
12
23
Benign
0
0
0
1
1
Conflicting
2
Total52091013239

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ABCA2 · 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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