ABCA2

Chr 9AR

ATP binding cassette subfamily A member 2

Also known as: ABC2, IDPOGSA

NCBI Gene: 20 ENSG00000107331 UniProt: Q9BZC7 OMIM: 600047

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intracellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the ABC1 subfamily. Members of the ABC1 subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes. This protein is highly expressed in brain tissue and may play a role in macrophage lipid metabolism and neural development. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.171 OMIM phenotype

Clinical Summary— ABCA2

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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.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 31 VUS of 99 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.17LOEUF

pLI 1.000

Z-score 8.92

OE 0.10 (0.07–0.17)

Highly constrained

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

Missense Constraint?

4.91Z-score

OE missense 0.65 (0.62–0.69)

1029 obs / 1578.1 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.10 (0.07–0.17)

0≤0.351.4

Missense OE?0.65 (0.62–0.69)

0≤0.61.4

Synonymous OE?1.16

0≤1.21.6

LoF obs/exp: 12 / 115.3Missense obs/exp: 1029 / 1578.1Syn Z: -3.36

ClinVar Variant Classifications

99 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1

VUS31

Likely Benign11

Likely Pathogenic

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	1	0	0	0	1
VUS	0	30	1	0	31
Likely Benign	0	4	1	6	11
Benign	0	0	0	0	0
Total	1	34	2	6	43

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

View in ClinVar →

1 pathogenic / likely-pathogenic (of 1) ClinVar copy-number / structural variants overlap ABCA2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →