ABCD3

Chr 1ARAD

ATP binding cassette subfamily D member 3

Also known as: ABC43, CBAS5, OPDM5, PMP70, PXMP1, ZWS2

This ATP-binding cassette transporter catalyzes the transport of long-chain fatty acids, dicarboxylic acids, and bile acids from the cytosol into peroxisomes for beta-oxidation. Mutations cause congenital bile acid synthesis defect type 5 and oculopharyngodistal myopathy type 5, inherited in either autosomal recessive or autosomal dominant patterns. The gene is moderately constrained against loss-of-function variants (LOEUF 0.435), reflecting its important role in peroxisomal fatty acid metabolism.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismAR/ADLOEUF 0.432 OMIM phenotypes
Clinical SummaryABCD3
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Gene-Disease Validity (ClinGen)
congenital bile acid synthesis defect 5 · ARLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.
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ClinVar Variants
9 unique Pathogenic / Likely Pathogenic· 121 VUS of 247 total submissions
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Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.43LOEUF
pLI 0.008
Z-score 4.75
OE 0.28 (0.180.43)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.54Z-score
OE missense 0.63 (0.560.70)
229 obs / 366.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.28 (0.180.43)
00.351.4
Missense OE0.63 (0.560.70)
00.61.4
Synonymous OE0.91
01.21.6
LoF obs/exp: 14 / 50.3Missense obs/exp: 229 / 366.0Syn Z: 0.82
DN
0.78top 25%
GOF
0.7127th %ile
LOF
0.2678th %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

247 submitted variants in ClinVar

Classification Summary

Pathogenic8
Likely Pathogenic1
VUS121
Likely Benign72
Benign22
Conflicting1
8
Pathogenic
1
Likely Pathogenic
121
VUS
72
Likely Benign
22
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
7
0
8
Likely Pathogenic
0
0
1
0
1
VUS
7
104
9
1
121
Likely Benign
1
1
39
31
72
Benign
0
1
16
5
22
Conflicting
1
Total91067237225

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

View in ClinVar →

Protein Context — Lollipop Plot

ABCD3 · 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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