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8 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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ACBD4
acyl-CoA binding domain containing 4
Chromosome 17 · 17q21.31
NCBI Gene: 79777Ensembl: ENSG00000181513.15HGNC: HGNC:23337UniProt: A0A0S2Z5Q0
26PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
fatty-acyl-CoA bindingfatty acid metabolic processcytoplasmneurodegenerative diseaseessential hypertensionHeadachehypertension
✦AI Summary

ACBD4 (acyl-CoA binding domain containing 4) is a peroxisomal tail-anchored membrane protein that binds medium- and long-chain acyl-CoA esters and functions as an intracellular carrier of these lipid molecules 1. Primary to its function, ACBD4 interacts with the endoplasmic reticulum (ER) protein VAPB via its FFAT motif to promote peroxisome-ER membrane contact sites 12, though this tethering function appears distinct from ACBD5. Unlike ACBD5, loss of ACBD4 does not reduce peroxisome-ER connections or cause very-long-chain fatty acid (VLCFA) accumulation; instead, ACBD4 loss increases the rate of VLCFA β-oxidation, suggesting regulatory rather than primary tethering roles 3. ACBD4 expression is modulated in lipid metabolism contexts, including upregulation in fatty liver development 4. Genetically, ACBD4 is a pleiotropic locus influencing hippocampal volumes and correlates with neuropsychiatric traits including Parkinson's disease risk 5. ACBD4 is also a novel p53-responsive gene activated during p53-dependent stress responses 6. These findings establish ACBD4 as a multifunctional regulator at the peroxisome-ER interface with roles in cellular lipid metabolism and neuropsychiatric disease susceptibility.

Sources cited
1
ACBD4 is a peroxisomal membrane protein that interacts with ER protein VAPB to promote peroxisome-ER associations
PMID: 28463579
2
ACBD4 loss increases VLCFA β-oxidation rate and has regulatory functions distinct from ACBD5's tethering role
PMID: 37414147
3
ACBD4 contains FFAT motif for peroxisome-ER tethering and differs functionally from ACBD5
PMID: 39271061
4
ACBD4 is upregulated in fatty liver development through gut-liver axis mechanisms
PMID: 40570459
5
ACBD4 is a pleiotropic locus influencing hippocampal volumes and associated with neuropsychiatric traits including Parkinson's disease risk
PMID: 39394562
6
ACBD4 is a novel p53-responsive gene activated in p53-dependent stress responses
PMID: 23284922
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.46Moderate
essential hypertensionOpen Targets
0.22Weak
HeadacheOpen Targets
0.21Weak
hypertensionOpen Targets
0.19Weak
insomniaOpen Targets
0.12Weak
osteoarthritisOpen Targets
0.11Weak
Abnormality of the skeletal systemOpen Targets
0.09Suggestive
hepatocellular carcinomaOpen Targets
0.08Suggestive
femur fractureOpen Targets
0.05Suggestive
neoplasmOpen Targets
0.04Suggestive
intelligenceOpen Targets
0.04Suggestive
Abnormal thrombosisOpen Targets
0.03Suggestive
respiratory system diseaseOpen Targets
0.03Suggestive
deep vein thrombosisOpen Targets
0.03Suggestive
allergic diseaseOpen Targets
0.03Suggestive
liver cancerOpen Targets
0.01Suggestive
cytomegalovirus infectionOpen Targets
0.01Suggestive
cancerOpen Targets
0.00Suggestive
colorectal carcinomaOpen Targets
0.00Suggestive
infectionOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CYP4B1Shared pathway100%PCCAShared pathway100%ECHDC3Shared pathway100%ACBD7Shared pathway100%AASDHShared pathway100%VAPBProtein interaction91%
Tissue Expression6 tissues
Liver
100%
Ovary
24%
Lung
11%
Heart
11%
Bone Marrow
8%
Brain
4%
Gene Interaction Network
Click a node to explore
ACBD4CYP4B1PCCAECHDC3ACBD7AASDHVAPB
PROTEIN STRUCTURE
Preparing viewer…
PDB2WH5 · 2.60 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.09LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.84 [0.65–1.09]
RankingsWhere ACBD4 stands among ~20K protein-coding genes
  • #12,723of 20,598
    Most Researched26
  • #11,102of 17,882
    Most Constrained (LOEUF)1.09
Genes detectedACBD4
Sources retrieved8 papers
Response time—
📄 Sources
8▼
1
Differential roles for ACBD4 and ACBD5 in peroxisome-ER interactions and lipid metabolism.
PMID: 37414147
J Biol Chem · 2023
1.00
2
Genetic architectures of the human hippocampus and those involved in neuropsychiatric traits.
PMID: 39394562
BMC Med · 2024
0.88
3
Peroxisomal ACBD4 interacts with VAPB and promotes ER-peroxisome associations.
PMID: 28463579
Cell Cycle · 2017
0.75
4
Multi-omics analysis provides new insights into molecular mechanisms for waterfowl fatty liver formation.
PMID: 40570459
Poult Sci · 2025
0.63
5
Identification and validation of novel prognostic fatty acid metabolic gene signatures in colon adenocarcinoma through systematic approaches.
PMID: 38186579
Oncol Res · 2023
0.50