ACBD5

Chr 10AR

acyl-CoA binding domain containing 5

Also known as: RDLKD

NCBI Gene: 91452 ENSG00000107897 UniProt: Q5T8D3 OMIM: 616618

The protein binds medium- and long-chain acyl-CoA esters and serves as the peroxisome receptor for pexophagy (selective autophagy of peroxisomes). Biallelic mutations cause retinal dystrophy with leukodystrophy, inherited in an autosomal recessive pattern. This gene is highly constrained against loss-of-function variants (LOEUF 0.53), reflecting its essential role in peroxisome homeostasis.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Retinal dystrophy with leukodystrophyMIM #618863

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · acyl-CoA binding domain containing protein 5 deficiency · AR · ClinGen 2024

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.53

LOEUF

LOF

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

0.87Z-score

OE missense 0.86 (0.77–0.95)

246 obs / 287.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.31 (0.19–0.53)

0≤0.351.4

Missense OE?0.86 (0.77–0.95)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 10 / 32.0Missense obs/exp: 246 / 287.7Syn Z: -0.46

Background carrier burden — how many people carry a rare variant somewhere in ACBD5?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 78

719 rare PASS variants

Rare truncating (LoF)

1 in 1,000

104 rare PASS variants

Rare synonymous (reference)

1 in 290

245 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ACBD5. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 130	1 in 990
South Asian	~43k	1 in 65	1 in 420
Remaining (unassigned)	~30k	1 in 80	1 in 420
European (Finnish)	~27k	1 in 270	≈ 1 in 6,600
Admixed American	~22k	1 in 62	1 in 870
African / African American	~21k	1 in 65	1 in 1,300
East Asian	~20k	1 in 74	1 in 730
Ashkenazi Jewish	~13k	1 in 220	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 87	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 12 of 13 coding exons well covered in gnomAD exomes; exon 8 marginal. Genomes: all 13.? see exons ↓