ACBD5

Chr 10AR

acyl-CoA binding domain containing 5

Also known as: RDLKD

NCBI Gene: 91452ENSG00000107897UniProt: Q5T8D3

This gene encodes a member of the acyl-Coenzyme A binding protein family, known to function in the transport and distribution of long chain acyl-Coenzyme A in cells. This gene may play a role in the differentiation of megakaryocytes and formation of platelets. A related protein in yeast is involved in autophagy of peroxisomes. A mutation in this gene has been associated with autosomal dominant thrombocytopenia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

Primary Disease Associations & Inheritance

Retinal dystrophy with leukodystrophyMIM #618863
AR
486
ClinVar variants
40
Pathogenic / LP
0.01
pLI score
1
Active trials
Clinical Summary— ACBD5
🧬
Gene-Disease Validity (ClinGen)
acyl-CoA binding domain containing protein 5 deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.
📋
ClinVar Variants
40 Pathogenic / Likely Pathogenic· 200 VUS of 486 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

pubmed: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.53LOEUF
pLI 0.006
Z-score 3.61
OE 0.31 (0.19–0.53)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.87Z-score
OE missense 0.86 (0.77–0.95)
246 obs / 287.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.31 (0.19–0.53)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.86 (0.77–0.95)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.06
0≤1.21.6
LoF obs/exp: 10 / 32.0Missense obs/exp: 246 / 287.7Syn Z: -0.46

ClinVar Variant Classifications

486 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic26
Likely Pathogenic14
VUS200
Likely Benign151
Benign87
Conflicting8
26
Pathogenic
14
Likely Pathogenic
200
VUS
151
Likely Benign
87
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
0
20
0
26
Likely Pathogenic
9
0
5
0
14
VUS
4
168
23
5
200
Likely Benign
0
8
64
79
151
Benign
0
7
72
8
87
Conflicting
—8
Total1918318492486

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

View in ClinVar →

Protein Context — Lollipop Plot

ACBD5 · protein map & ClinVar variants

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

Gene2Phenotype Curations

ACBD5-related deficiency

strong
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Retinal dystrophy with leukodystrophy

MIM #618863

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Local accumulation of very long-chain PUFA in plexiform layers associates with retinal dysfunction in a mouse model of peroxisomal ACBD5-deficiency.
Merz J et al.·Cell Mol Life Sci
2025🔓 Open AccessFunctional
The neurological pathology of peroxisomal ACBD5 deficiency - lessons from patients and mouse models.
Dawes ML et al.·Front Mol Neurosci
2025🔓 Open AccessCohort
ACOT12, a novel factor in the pathogenesis of kidney fibrosis, modulates ACBD5.
Kim EH et al.·Exp Mol Med
2025🔓 Open Access
Ataxia with giant axonopathy in Acbd5-deficient mice halted by adeno-associated virus gene therapy.
Granadeiro L et al.·Brain
2024
A Novel Homozygous ACBD5 Variant in an Emerging Peroxisomal Disorder Presenting with Retinal Dystrophy and a Review of the Literature.
Hasturk BA et al.·Mol Syndromol
2024Review
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Peroxisome Biogenesis DisorderZellweger Spectrum DisorderRCDP - Rhizomelic Chondrodysplasia Punctata

Longitudinal Natural History Study of Patients With Peroxisome Biogenesis Disorders (PBD)

RECRUITING
NCT01668186McGill University Health Centre/Research Institute of the McGill University Health CentreStarted 2012-01

External Resources

Links to major genomics databases and tools