ACBD4

Summary

ACBD4 (acyl-CoA binding domain containing 4, HGNC:23337) is a protein-coding gene on chromosome 17q21.31, encoding Acyl-CoA-binding domain-containing protein 4 (Q8NC06). Binds medium- and long-chain acyl-CoA esters and may function as an intracellular carrier of acyl-CoA esters.

This gene encodes a member of the acyl-coenzyme A binding domain containing protein family. All family members contain the conserved acyl-Coenzyme A binding domain, which binds acyl-CoA thiol esters. They are thought to play roles in acyl-CoA dependent lipid metabolism. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 79777 — RefSeq curated summary.

At a glance

• GWAS associations: 18
• Clinical variants (ClinVar): 102 total — 2 pathogenic
• MANE Select transcript: NM_001135705

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23337
Approved symbol	ACBD4
Name	acyl-CoA binding domain containing 4
Location	17q21.31
Locus type	gene with protein product
Status	Approved
Aliases	FLJ13322
Ensembl gene	ENSG00000181513
Ensembl biotype	protein_coding
OMIM	619968
Entrez	79777

Gene structure

Transcript identifiers

Ensembl transcripts: 50 — 42 protein_coding, 4 protein_coding_CDS_not_defined, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000321854, ENST00000376955, ENST00000398322, ENST00000431281, ENST00000585553, ENST00000586279, ENST00000586346, ENST00000587111, ENST00000587976, ENST00000589752, ENST00000589798, ENST00000590289, ENST00000591136, ENST00000591859, ENST00000592162, ENST00000619916, ENST00000865130, ENST00000865131, ENST00000865132, ENST00000865133, ENST00000865134, ENST00000865135, ENST00000865136, ENST00000865137, ENST00000865138, ENST00000865139, ENST00000865140, ENST00000865141, ENST00000865142, ENST00000865143, ENST00000865144, ENST00000865145, ENST00000865146, ENST00000865147, ENST00000865148, ENST00000865149, ENST00000865150, ENST00000865151, ENST00000865152, ENST00000865153, ENST00000912230, ENST00000912231, ENST00000912232, ENST00000941066, ENST00000941067, ENST00000941068, ENST00000941069, ENST00000941070, ENST00000941071, ENST00000941072

RefSeq mRNA: 9 — MANE Select: NM_001135705 NM_001135705, NM_001135706, NM_001135707, NM_001321352, NM_001321353, NM_001378111, NM_001378112, NM_001411125, NM_024722

CCDS: CCDS42348, CCDS45710, CCDS45711, CCDS92338

Canonical transcript exons

ENST00000321854 — 10 exons

Exon	Start	End
ENSE00002931828	45135687	45135953
ENSE00003486152	45137760	45137830
ENSE00003492764	45137019	45137139
ENSE00003494515	45137913	45137988
ENSE00003511183	45143443	45144176
ENSE00003536855	45139021	45139160
ENSE00003538500	45136692	45136776
ENSE00003563599	45137368	45137454
ENSE00003570767	45136108	45136232
ENSE00003651106	45136500	45136620

Expression profiles

Bgee: expression breadth ubiquitous, 200 present calls, max score 95.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.2499 / max 68.7528, expressed in 1702 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
161234	5.3683	1627
161233	1.8815	820

Top tissues by expression

270 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	95.33	gold quality
mucosa of stomach	UBERON:0001199	90.50	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.16	gold quality
mucosa of transverse colon	UBERON:0004991	89.84	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.52	gold quality
descending thoracic aorta	UBERON:0002345	89.49	gold quality
right coronary artery	UBERON:0001625	89.41	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	89.37	gold quality
endocervix	UBERON:0000458	89.19	gold quality
thoracic aorta	UBERON:0001515	89.13	gold quality
ascending aorta	UBERON:0001496	89.12	gold quality
lower esophagus muscularis layer	UBERON:0035833	89.12	gold quality
lower esophagus	UBERON:0013473	89.09	gold quality
right uterine tube	UBERON:0001302	89.01	gold quality
left uterine tube	UBERON:0001303	89.01	gold quality
muscle layer of sigmoid colon	UBERON:0035805	88.98	gold quality
left ovary	UBERON:0002119	88.90	gold quality
right lobe of thyroid gland	UBERON:0001119	88.86	gold quality
cerebellar hemisphere	UBERON:0002245	88.85	gold quality
left lobe of thyroid gland	UBERON:0001120	88.79	gold quality
aorta	UBERON:0000947	88.74	gold quality
popliteal artery	UBERON:0002250	88.69	gold quality
tibial artery	UBERON:0007610	88.69	gold quality
cerebellar cortex	UBERON:0002129	88.57	gold quality
small intestine	UBERON:0002108	88.53	gold quality
right adrenal gland	UBERON:0001233	88.34	gold quality
body of uterus	UBERON:0009853	88.34	gold quality
body of pancreas	UBERON:0001150	88.17	gold quality
tibial nerve	UBERON:0001323	88.16	gold quality
liver	UBERON:0002107	88.12	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.25

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

25 targeting ACBD4, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-3606-5P	99.31	69.67	1168
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-146B-3P	97.83	65.29	782
HSA-MIR-647	97.73	67.79	927
HSA-MIR-3127-5P	97.52	65.24	786
HSA-MIR-6824-5P	97.41	68.43	583
HSA-MIR-1237-5P	95.38	62.21	451
HSA-MIR-6889-5P	90.26	64.13	291
HSA-MIR-6777-5P	88.76	62.64	222

Literature-anchored findings (GeneRIF, showing 2)

• acyl-CoA binding domain protein 4 (ACBD4) as a tail-anchored peroxisomal membrane protein which interacts with the endoplasmic reticulum (ER) protein, vesicle-associated membrane protein-associated protein-B (VAPB) to promote peroxisome-ER associations. (PMID:28463579)
• Differential roles for ACBD4 and ACBD5 in peroxisome-ER interactions and lipid metabolism. (PMID:37414147)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	acbd4	ENSDARG00000027070
mus_musculus	Acbd4	ENSMUSG00000056938
rattus_norvegicus	Acbd4	ENSRNOG00000003108
drosophila_melanogaster	Acbp2	FBGN0010387
drosophila_melanogaster	CG8814	FBGN0031478
caenorhabditis_elegans	acbp-1	WBGENE00016655

Paralogs (4): ACBD5 (ENSG00000107897), DBI (ENSG00000155368), ACBD7 (ENSG00000176244), ECI2 (ENSG00000198721)

Protein

Protein identifiers

Acyl-CoA-binding domain-containing protein 4 — Q8NC06 (reviewed: Q8NC06)

All UniProt accessions (6): Q8NC06, A0A0S2Z5Q0, A0A0S2Z5W7, A0A0S2Z5Y4, K7EM05, K7EMH4

UniProt curated annotations — full annotation on UniProt →

Function. Binds medium- and long-chain acyl-CoA esters and may function as an intracellular carrier of acyl-CoA esters.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8NC06-1	1	yes
Q8NC06-2	2
Q8NC06-3	3

RefSeq proteins (9): NP_001129177, NP_001129178, NP_001129179, NP_001308281, NP_001308282, NP_001365040, NP_001365041, NP_001398054, NP_078998 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000582	Acyl-CoA-binding_protein	Domain
IPR014352	FERM/acyl-CoA-bd_prot_sf	Homologous_superfamily
IPR022408	Acyl-CoA-binding_prot_CS	Conserved_site
IPR035984	Acyl-CoA-binding_sf	Homologous_superfamily

Pfam: PF00887

UniProt features (21 total): helix 4, binding site 4, splice variant 3, sequence variant 2, modified residue 2, chain 1, domain 1, sequence conflict 1, turn 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2WH5	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NC06-F1	65.38	0.24

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (4): 23–32; 43–47; 69; 88

Post-translational modifications (2): 166, 171

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-390918	Peroxisomal lipid metabolism
R-HSA-1430728	Metabolism
R-HSA-556833	Metabolism of lipids
R-HSA-8978868	Fatty acid metabolism

MSigDB gene sets: 109 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, CCANNAGRKGGC_UNKNOWN, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_DN, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, GOBP_LIPID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, OCT1_B, CHIANG_LIVER_CANCER_SUBCLASS_PROLIFERATION_DN, CTGAGCC_MIR24, GOBP_FATTY_ACID_METABOLIC_PROCESS, GOMF_SULFUR_COMPOUND_BINDING, YATGNWAAT_OCT_C, GOMF_AMIDE_BINDING, GOMF_LIPID_BINDING

GO Biological Process (1): fatty acid metabolic process (GO:0006631)

GO Molecular Function (3): fatty-acyl-CoA binding (GO:0000062), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (2): cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Fatty acid metabolism	1
Metabolism	1
Metabolism of lipids	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
cellular anatomical structure	2
lipid metabolic process	1
monocarboxylic acid metabolic process	1
acyl-CoA binding	1
fatty acid derivative binding	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

790 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACBD4	VAPB	O95292	958
ACBD4	VAPA	Q9P0L0	870
ACBD4	DCAKD	Q8WVC6	448
ACBD4	PEX11B	O96011	441
ACBD4	RUSC1	Q9BVN2	421
ACBD4	PEX11G	Q96HA9	403
ACBD4	PEX26	Q7Z412	399
ACBD4	ACBD6	Q9BR61	396
ACBD4	NFS1	Q9Y697	386
ACBD4	PPP1R3F	Q6ZSY5	385
ACBD4	GLRX5	Q86SX6	385
ACBD4	RMDN3	Q96TC7	382
ACBD4	PEX11A	O75192	381
ACBD4	PEX5	P50542	377
ACBD4	PEX3	P56589	376

IntAct

6 interactions, top by confidence:

A	B	Type	Score
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
LPCAT1	GLB1	psi-mi:“MI:0914”(association)	0.350
VAPA	ESYT2	psi-mi:“MI:0914”(association)	0.350
VAPB	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (18): ACBD4 (Affinity Capture-MS), ACBD4 (Affinity Capture-MS), ACBD4 (Affinity Capture-MS), MEOX2 (Two-hybrid), CRX (Two-hybrid), MEOX1 (Two-hybrid), REL (Two-hybrid), KIF9 (Two-hybrid), ACBD4 (Two-hybrid), ACBD4 (Two-hybrid), ACBD4 (Two-hybrid), ACBD4 (Proximity Label-MS), ACBD4 (Proximity Label-MS), ACBD4 (Affinity Capture-MS), ACBD4 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GVZ6, A0JNN6, A2A9F4, A6NDZ8, A6NE82, A6NJ08, A6NJB7, A7MB40, A8MQ03, D2HS03, O43151, O93343, O94850, O95886, P01099, P97838, Q00587, Q0VBZ8, Q2KJ10, Q2M2S6, Q3KP66, Q58CU6, Q5NCP0, Q5RBE4, Q64322, Q68DV7, Q6AY88, Q6PFD5, Q7TN12, Q80V38, Q86YN6, Q86YV5, Q8BFY7, Q8BG87, Q8NAX2, Q8NC06, Q8NHZ7, Q8TEF2, Q91XA5, Q96EL1

Diamond homologs: A0FKI7, A2VDR2, A5WV69, O01805, O04066, O09035, O22643, O75521, P07106, P07107, P07108, P11030, P12026, P31786, P31787, P42281, P45882, P45883, P56702, P57752, P61867, P61868, P82934, Q20507, Q2KHT9, Q39315, Q39779, Q3SZF0, Q4V869, Q4V8X4, Q502L1, Q54GC8, Q5FXM5, Q5R7P6, Q5R7V3, Q5RJK8, Q5T8D3, Q5VRM0, Q5XG73, Q5XIC0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

102 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	70
Likely benign	11
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
3341110	GRCh37/hg19 17q21.31(chr17:42927777-43706954)x1	Pathogenic
59587	GRCh38/hg38 17q21.31(chr17:44928498-45299730)x1	Pathogenic

SpliceAI

1354 predictions. Top by Δscore:

Variant	Effect	Δscore
17:45136773:GAAG:G	donor_gain	1.0000
17:45136774:AAGG:A	donor_loss	1.0000
17:45136775:AGGT:A	donor_loss	1.0000
17:45136776:GGTAA:G	donor_loss	1.0000
17:45136777:G:A	donor_loss	1.0000
17:45136778:T:G	donor_loss	1.0000
17:45137134:TCAC:T	donor_gain	1.0000
17:45137759:GA:G	acceptor_gain	1.0000
17:45137910:CAGGT:C	acceptor_loss	1.0000
17:45137984:GAAAG:G	donor_gain	1.0000
17:45137986:AAGGT:A	donor_loss	1.0000
17:45137987:AGGT:A	donor_loss	1.0000
17:45137990:T:G	donor_loss	1.0000
17:45136228:GAACG:G	donor_gain	0.9900
17:45136271:G:GT	donor_gain	0.9900
17:45136618:GTG:G	donor_gain	0.9900
17:45136777:G:GG	donor_gain	0.9900
17:45137013:CTACA:C	acceptor_loss	0.9900
17:45137014:TACA:T	acceptor_loss	0.9900
17:45137172:C:G	donor_gain	0.9900
17:45137364:GCAGG:G	acceptor_loss	0.9900
17:45137365:CAGGT:C	acceptor_loss	0.9900
17:45137366:AGGT:A	acceptor_loss	0.9900
17:45137367:G:GT	acceptor_loss	0.9900
17:45137450:CCCAG:C	donor_loss	0.9900
17:45137451:CCAGG:C	donor_loss	0.9900
17:45137452:CAG:C	donor_loss	0.9900
17:45137453:AGGT:A	donor_loss	0.9900
17:45137454:GGT:G	donor_loss	0.9900
17:45137455:G:C	donor_loss	0.9900

AlphaMissense

1985 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:45136552:G:C	K47N	0.999
17:45136552:G:T	K47N	0.999
17:45136618:G:C	K69N	0.999
17:45136618:G:T	K69N	0.999
17:45136190:T:C	F16L	0.998
17:45136191:T:C	F16S	0.998
17:45136192:C:A	F16L	0.998
17:45136192:C:G	F16L	0.998
17:45136692:G:C	W70C	0.998
17:45136692:G:T	W70C	0.998
17:45136699:T:A	W73R	0.998
17:45136699:T:C	W73R	0.998
17:45136701:G:C	W73C	0.998
17:45136701:G:T	W73C	0.998
17:45136530:T:C	L40P	0.997
17:45136616:A:G	K69E	0.997
17:45136619:T:A	W70R	0.997
17:45136619:T:C	W70R	0.997
17:45136696:G:C	A72P	0.997
17:45136556:G:C	A49P	0.996
17:45136744:T:G	Y88D	0.996
17:45136191:T:G	F16C	0.995
17:45136536:T:C	F42S	0.995
17:45136555:G:C	Q48H	0.995
17:45136555:G:T	Q48H	0.995
17:45136700:G:C	W73S	0.995
17:45136744:T:C	Y88H	0.995
17:45136535:T:C	F42L	0.994
17:45136537:C:A	F42L	0.994
17:45136537:C:G	F42L	0.994

dbSNP variants (sampled 300 via entrez): RS1000037052 (17:45132545 G>C,T), RS1000165344 (17:45136307 T>C), RS1000499129 (17:45130704 C>T), RS1000762805 (17:45142971 T>C), RS1001063151 (17:45132259 A>G), RS1001298427 (17:45129909 G>A), RS1001478280 (17:45135636 T>C), RS1001535212 (17:45131920 C>T), RS1001545846 (17:45142309 C>A), RS1001660365 (17:45138399 T>C), RS1001770759 (17:45129698 G>A), RS1001777184 (17:45138849 A>G), RS1002373674 (17:45131124 T>C), RS1002706679 (17:45131471 T>A,C), RS1002748861 (17:45140055 A>T)

Disease associations

OMIM: gene MIM:619968 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (1): Genetic syndromic Pierre Robin syndrome (Orphanet:363294)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST000395_1	Systolic blood pressure	1.000000e-08
GCST000817_85	Height	2.000000e-16
GCST001519_9	Economic and political preferences	2.000000e-06
GCST002647_121	Height	8.000000e-27
GCST002702_1	Height	3.000000e-06
GCST003981_5	Insomnia	3.000000e-07
GCST004412_12	Craniofacial microsomia	9.000000e-06
GCST006661_255	Male-pattern baldness	2.000000e-22
GCST006941_17	Irritable mood	3.000000e-13
GCST006943_20	Feeling miserable	8.000000e-13
GCST006945_1	Feeling guilty	6.000000e-10
GCST006946_15	Worry too long after an embarrassing experience	2.000000e-08
GCST006947_23	Feeling fed-up	1.000000e-17
GCST008839_299	Height	3.000000e-11
GCST008916_39	Asthma	8.000000e-12
GCST010703_91	Brain morphology (MOSTest)	2.000000e-65
GCST90020026_439	Hip index	4.000000e-13
GCST90020028_1376	Hip circumference adjusted for BMI	4.000000e-15

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0004827	economic and social preference
EFO:0007876	insomnia measurement
EFO:0009594	irritability measurement
EFO:0009598	feeling miserable measurement
EFO:0009595	guilt measurement
EFO:0009589	worry measurement
EFO:0009588	feeling “fed-up” measurement
EFO:0004346	neuroimaging measurement
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs12946454	ACBD4, PLCD3	3	3.00	1	diltiazem

CTD chemical–gene interactions

33 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation	2
Testosterone	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Cyclosporine	decreases expression, decreases methylation	2
GSK-J4	decreases expression	1
FR900359	affects phosphorylation	1
pirinixic acid	affects binding, increases activity, increases expression	1
beta-lapachone	decreases expression	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
jinfukang	affects cotreatment, increases expression	1
Zoledronic Acid	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	affects methylation, increases abundance	1
Calcitriol	increases expression, affects cotreatment	1
Cisplatin	affects cotreatment, increases expression	1
Estradiol	affects cotreatment, decreases expression	1
Lead	affects expression	1
N-Nitrosopyrrolidine	decreases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Toluene	increases methylation, decreases expression	1
Triiodothyronine	decreases expression	1
Urethane	decreases expression	1
Aflatoxin B1	affects expression	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.