ACBD5

Summary

ACBD5 (acyl-CoA binding domain containing 5, HGNC:23338) is a protein-coding gene on chromosome 10p12.1, encoding Acyl-CoA-binding domain-containing protein 5 (Q5T8D3). Acyl-CoA binding protein which acts as the peroxisome receptor for pexophagy but is dispensable for aggrephagy and nonselective autophagy.

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.

Source: NCBI Gene 91452 — RefSeq curated summary.

At a glance

• Gene–disease (curated): acyl-CoA binding domain containing protein 5 deficiency (Definitive, ClinGen) — +1 more curated relationship
• Clinical variants (ClinVar): 472 total — 17 pathogenic, 12 likely-pathogenic
• Phenotypes (HPO): 19
• MANE Select transcript: NM_145698

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23338
Approved symbol	ACBD5
Name	acyl-CoA binding domain containing 5
Location	10p12.1
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp434A2417, KIAA1996
Ensembl gene	ENSG00000107897
Ensembl biotype	protein_coding
OMIM	616618
Entrez	91452

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 26 protein_coding, 3 nonsense_mediated_decay, 1 retained_intron

ENST00000375888, ENST00000375897, ENST00000375901, ENST00000375905, ENST00000396271, ENST00000412279, ENST00000426079, ENST00000476758, ENST00000676511, ENST00000676599, ENST00000676648, ENST00000676731, ENST00000676732, ENST00000676997, ENST00000677141, ENST00000677200, ENST00000677248, ENST00000677311, ENST00000677440, ENST00000677441, ENST00000677509, ENST00000677667, ENST00000677901, ENST00000677902, ENST00000677960, ENST00000678392, ENST00000678446, ENST00000679220, ENST00000679293, ENST00000958744

RefSeq mRNA: 28 — MANE Select: NM_145698 NM_001042473, NM_001271512, NM_001301251, NM_001301252, NM_001301253, NM_001301254, NM_001352568, NM_001352569, NM_001352570, NM_001352571, NM_001352572, NM_001352573, NM_001352574, NM_001352575, NM_001352576, NM_001352577, NM_001352578, NM_001352579, NM_001352580, NM_001352581, NM_001352582, NM_001352583, NM_001352584, NM_001352585, NM_001352586, NM_001352587, NM_001352588, NM_145698

CCDS: CCDS44368, CCDS7154, CCDS73079, CCDS76290, CCDS86078, CCDS91226, CCDS91227, CCDS91229, CCDS91230

Canonical transcript exons

ENST00000396271 — 13 exons

Exon	Start	End
ENSE00001287161	27235092	27235212
ENSE00001468751	27240674	27240797
ENSE00001672657	27204440	27204549
ENSE00003463289	27208246	27208445
ENSE00003486115	27215535	27215641
ENSE00003531119	27231748	27231820
ENSE00003572079	27210814	27211081
ENSE00003605766	27240319	27240484
ENSE00003607295	27205198	27205248
ENSE00003636077	27223338	27223452
ENSE00003637735	27219723	27219857
ENSE00003754449	27195214	27197442
ENSE00003789369	27217980	27218183

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 98.55.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.9906 / max 287.0723, expressed in 1793 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
108758	4.2165	1529
108755	3.7881	1364
108760	2.2220	1078
108756	1.9551	1124
108761	0.9674	382
108759	0.4297	166
108757	0.4119	164

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	98.55	gold quality
left ventricle myocardium	UBERON:0006566	98.39	gold quality
lateral globus pallidus	UBERON:0002476	97.92	gold quality
subthalamic nucleus	UBERON:0001906	97.83	gold quality
medulla oblongata	UBERON:0001896	97.81	gold quality
inferior vagus X ganglion	UBERON:0005363	97.50	gold quality
ileal mucosa	UBERON:0000331	97.44	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.44	gold quality
dorsal plus ventral thalamus	UBERON:0001897	97.43	gold quality
superior vestibular nucleus	UBERON:0007227	97.41	gold quality
substantia nigra pars compacta	UBERON:0001965	97.27	gold quality
pons	UBERON:0000988	97.24	gold quality
pigmented layer of retina	UBERON:0001782	97.23	gold quality
Brodmann (1909) area 46	UBERON:0006483	97.18	gold quality
kidney epithelium	UBERON:0004819	97.17	gold quality
jejunum	UBERON:0002115	97.10	gold quality
heart right ventricle	UBERON:0002080	96.97	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.94	gold quality
myocardium	UBERON:0002349	96.86	gold quality
renal medulla	UBERON:0000362	96.83	gold quality
upper arm skin	UBERON:0004263	96.81	gold quality
endothelial cell	CL:0000115	96.45	gold quality
ventral tegmental area	UBERON:0002691	96.41	gold quality
deltoid	UBERON:0001476	96.24	gold quality
corpus callosum	UBERON:0002336	96.19	gold quality
cardiac muscle of right atrium	UBERON:0003379	96.08	gold quality
palpebral conjunctiva	UBERON:0001812	95.99	gold quality
cerebellar vermis	UBERON:0004720	95.98	gold quality
quadriceps femoris	UBERON:0001377	95.93	gold quality
postcentral gyrus	UBERON:0002581	95.92	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.79

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

156 targeting ACBD5, 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-5692A	100.00	74.40	6850
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488

Literature-anchored findings (GeneRIF, showing 11)

• A mutation in the acyl-coenzyme A binding domain-containing protein 5 gene (ACBD5 ) may have a role in autosomal dominant thrombocytopenia (PMID:20626622)
• Yeast Atg37, which is homologous to human ACBD5, is involved in autophagy of peroxisomes. (PMID:24905344)
• Findings suggest that the ACBD5-RET rearrangement is causatively involved in the development of papillary thyroid cancer. (PMID:25175022)
• ACBD5 captures VLC-CoAs on the cytosolic side of the peroxisomal membrane so that the transport of VLC-CoAs into peroxisomes and subsequent beta-oxidation thereof can proceed efficiently. (PMID:27899449)
• ACBD5-VAPB interaction regulates peroxisome-endoplasmic reticulum associations. Loss of PO-ER association perturbs PO membrane expansion and increases PO movement. (PMID:28108524)
• VAP-ACBD5-mediated contact between the endoplasmic reticulum and peroxisomes mediate organelle maintenance and lipid homeostasis. (PMID:28108526)
• Peroxisomal (PO) long range movements were largely diminished in response to human ACBD5 overexpression in primary mouse hippocampal neurons. PO localization significantly changed in ACBD5-transfected neurons, PO numbers in neurites increased, while PO density in the soma was decreased. Alterations in PO motility and distribution in the hippocampal neurons were independent of the interaction between ACBD5 and mouse Vapb. (PMID:30589881)
• First reported adult patient with retinal dystrophy and leukodystrophy caused by a novel ACBD5 variant: A case report and review of literature. (PMID:33427402)
• Newly defined peroxisomal disease with novel ACBD5 mutation. (PMID:34668366)
• Regulating peroxisome-ER contacts via the ACBD5-VAPB tether by FFAT motif phosphorylation and GSK3beta. (PMID:35019937)
• Differential roles for ACBD4 and ACBD5 in peroxisome-ER interactions and lipid metabolism. (PMID:37414147)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	acbd5a	ENSDARG00000034883
danio_rerio	acbd5b	ENSDARG00000058410
mus_musculus	Acbd5	ENSMUSG00000026781
rattus_norvegicus	Acbd5	ENSRNOG00000017642
rattus_norvegicus	AABR07046657.1	ENSRNOG00000022709
drosophila_melanogaster	Acbp2	FBGN0010387
drosophila_melanogaster	CG8814	FBGN0031478
caenorhabditis_elegans	acbp-1	WBGENE00016655

Paralogs (4): DBI (ENSG00000155368), ACBD7 (ENSG00000176244), ACBD4 (ENSG00000181513), ECI2 (ENSG00000198721)

Protein

Protein identifiers

Acyl-CoA-binding domain-containing protein 5 — Q5T8D3 (reviewed: Q5T8D3)

All UniProt accessions (21): Q5T8D3, A0A087X0B8, A0A7I2V2M2, A0A7I2V2R8, A0A7I2V2Y9, A0A7I2V347, A0A7I2V420, A0A7I2V462, A0A7I2V556, A0A7I2V560, A0A7I2V5E1, A0A7I2V5L4, A0A7I2V5U2, A0A7I2V690, A0A7I2YQD7, A0A7I2YQE9, A0A7I2YQJ9, A0A7I2YQS1, B7Z2R7, Q5T8E0, X6RDD7

UniProt curated annotations — full annotation on UniProt →

Function. Acyl-CoA binding protein which acts as the peroxisome receptor for pexophagy but is dispensable for aggrephagy and nonselective autophagy. Binds medium- and long-chain acyl-CoA esters.

Subcellular location. Peroxisome membrane.

Disease relevance. Retinal dystrophy with leukodystrophy (RDLKD) [MIM:618863] An autosomal recessive disorder characterized by progressive leukodystrophy associated with developmental delay, spastic paraparesis, ataxia, and retinal dystrophy. Patients may show facial dysmorphism. Laboratory investigations reveal an abnormal profile of very-long chain fatty acid in plasma. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the ATG37 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q5T8D3-1	1	yes
Q5T8D3-2	2
Q5T8D3-3	3
Q5T8D3-4	4

RefSeq proteins (28): NP_001035938, NP_001258441, NP_001288180, NP_001288181, NP_001288182, NP_001288183, NP_001339497, NP_001339498, NP_001339499, NP_001339500, NP_001339501, NP_001339502, NP_001339503, NP_001339504, NP_001339505, NP_001339506, NP_001339507, NP_001339508, NP_001339509, NP_001339510, NP_001339511, NP_001339512, NP_001339513, NP_001339514, NP_001339515, NP_001339516, NP_001339517, NP_663736* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000582	Acyl-CoA-binding_protein	Domain
IPR014352	FERM/acyl-CoA-bd_prot_sf	Homologous_superfamily
IPR016347	ACBD5	Family
IPR022408	Acyl-CoA-binding_prot_CS	Conserved_site
IPR035984	Acyl-CoA-binding_sf	Homologous_superfamily

Pfam: PF00887

UniProt features (40 total): modified residue 13, binding site 4, splice variant 4, helix 4, sequence conflict 3, compositionally biased region 3, region of interest 2, coiled-coil region 2, chain 1, transmembrane region 1, domain 1, sequence variant 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3FLV	X-RAY DIFFRACTION	1.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5T8D3-F1	57.49	0.17

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): 52–61; 72–76; 98; 117

Post-translational modifications (13): 193, 194, 196, 200, 215, 279, 313, 400, 428, 469, 137, 172, 63

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-390918	Peroxisomal lipid metabolism
R-HSA-8980692	RHOA GTPase cycle
R-HSA-9013106	RHOC GTPase cycle
R-HSA-9603798	Class I peroxisomal membrane protein import
R-HSA-1430728	Metabolism
R-HSA-162582	Signal Transduction
R-HSA-194315	Signaling by Rho GTPases
R-HSA-556833	Metabolism of lipids
R-HSA-8978868	Fatty acid metabolism
R-HSA-9012999	RHO GTPase cycle
R-HSA-9609507	Protein localization
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 233 (showing top): GOBP_FATTY_ACID_CATABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GGGTGGRR_PAX4_03, GGAMTNNNNNTCCY_UNKNOWN, GOBP_MACROAUTOPHAGY, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, GOBP_ORGANIC_ACID_CATABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_CATABOLIC_PROCESS, AACTTT_UNKNOWN, GOCC_MICROBODY_MEMBRANE, CUI_TCF21_TARGETS_2_DN, GOBP_MONOCARBOXYLIC_ACID_CATABOLIC_PROCESS, GOBP_LIPID_CATABOLIC_PROCESS

GO Biological Process (4): pexophagy (GO:0000425), fatty acid metabolic process (GO:0006631), fatty acid catabolic process (GO:0009062), autophagy (GO:0006914)

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

GO Cellular Component (6): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), peroxisome (GO:0005777), peroxisomal membrane (GO:0005778), cytosol (GO:0005829), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
RHO GTPase cycle	2
Fatty acid metabolism	1
Protein localization	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Metabolism	1
Metabolism of lipids	1
Signaling by Rho GTPases	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
binding	2
macroautophagy	1
autophagy of peroxisome	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
fatty acid metabolic process	1
lipid catabolic process	1
monocarboxylic acid catabolic process	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
acyl-CoA binding	1
fatty acid derivative binding	1
nuclear lumen	1
intracellular anatomical structure	1
microbody	1
peroxisome	1
microbody membrane	1
cytoplasm	1

Protein interactions and networks

STRING

1504 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACBD5	VAPB	O95292	991
ACBD5	VAPA	Q9P0L0	987
ACBD5	PEX16	Q9Y5Y5	690
ACBD5	PEX5	P50542	689
ACBD5	PEX3	P56589	589
ACBD5	ABCD1	P33897	558
ACBD5	ABCD3	P28288	554
ACBD5	PEX11B	O96011	550
ACBD5	PXMP2	Q9NR77	501
ACBD5	PEX14	O75381	491
ACBD5	HINT3	Q9NQE9	483
ACBD5	PEX11A	O75192	475
ACBD5	ANKRD26	Q9UPS8	474
ACBD5	PDZD8	Q8NEN9	471
ACBD5	ACBD7	Q8N6N7	460

IntAct

44 interactions, top by confidence:

A	B	Type	Score
BCL2	BCL2L11	psi-mi:“MI:0914”(association)	0.930
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
VAPA	FAM83G	psi-mi:“MI:0914”(association)	0.640
ZFPL1	PPP2R5E	psi-mi:“MI:0914”(association)	0.640
VAPA	PITPNM1	psi-mi:“MI:0914”(association)	0.640
CNGA3	C2CD2L	psi-mi:“MI:0914”(association)	0.530
vpr	AGPS	psi-mi:“MI:0914”(association)	0.460
VAPA		psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
BMI1	MEIS3P1	psi-mi:“MI:0914”(association)	0.350
NCAPD3	NDUFS8	psi-mi:“MI:0914”(association)	0.350
	AGPS	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
NECAB2	PCM1	psi-mi:“MI:0914”(association)	0.350
PRDM11	LONRF3	psi-mi:“MI:0914”(association)	0.350
CNGA3	MAGEA6	psi-mi:“MI:0914”(association)	0.350
FBXW11	HNRNPDL	psi-mi:“MI:0914”(association)	0.350
SAAL1	TMEM223	psi-mi:“MI:0914”(association)	0.350
ZFPL1	RAB3GAP1	psi-mi:“MI:0914”(association)	0.350
MFSD10	NDUFS8	psi-mi:“MI:0914”(association)	0.350
MFSD5	ILVBL	psi-mi:“MI:0914”(association)	0.350
NIPAL3	ILVBL	psi-mi:“MI:0914”(association)	0.350
SLC27A5	MEIOC	psi-mi:“MI:0914”(association)	0.350

BioGRID (266): ACBD5 (Affinity Capture-MS), ACBD5 (Affinity Capture-RNA), ACBD5 (Affinity Capture-RNA), ACBD5 (Affinity Capture-MS), ACBD5 (Affinity Capture-MS), ACBD5 (Proximity Label-MS), ACBD5 (Affinity Capture-MS), ACBD5 (Affinity Capture-MS), ACBD5 (Affinity Capture-MS), ACBD5 (Affinity Capture-MS), ACBD5 (Affinity Capture-MS), ACBD5 (Affinity Capture-MS), ACBD5 (Affinity Capture-MS), ACBD5 (Affinity Capture-MS), ACBD5 (Affinity Capture-MS)

ESM2 similar proteins: A0A2R6W1B1, A0FKI7, A2XC52, A2XTW9, A2Y0Q2, B8AMA8, B8B8I3, F4I9G2, O94972, P07106, P20067, P41135, P85828, Q5EAE9, Q5EAH9, Q5R7V3, Q5T8D3, Q5XEM9, Q5XG73, Q5XI67, Q6EPZ2, Q6GPE9, Q6IE24, Q6PCX9, Q70EL1, Q75IR6, Q76N89, Q7XUW3, Q84TV4, Q86UB2, Q8BJL1, Q8BL06, Q8CBX9, Q8H383, Q8H8C6, Q8K3A6, Q8K4P8, Q8LA16, Q8TB52, Q96S38

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

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

Classification	Count (floor)
Pathogenic	17
Likely pathogenic	12
Uncertain significance	192
Likely benign	147
Benign	85

Top pathogenic / likely-pathogenic (29)

Variant ID	HGVS	Classification
1069217	NM_145698.5(ACBD5):c.42G>A (p.Trp14Ter)	Pathogenic
1340583	GRCh37/hg19 10p12.1(chr10:27204530-29105882)x1	Pathogenic
1412967	NM_145698.5(ACBD5):c.78G>A (p.Trp26Ter)	Pathogenic
2022797	NM_145698.5(ACBD5):c.317C>A (p.Ser106Ter)	Pathogenic
2023818	NM_145698.5(ACBD5):c.1515G>A (p.Trp505Ter)	Pathogenic
2028352	NM_145698.5(ACBD5):c.460_461del (p.Lys154fs)	Pathogenic
2124271	NM_145698.5(ACBD5):c.10del (p.Leu4fs)	Pathogenic
242989	NM_145698.5(ACBD5):c.1204+1G>A	Pathogenic
2824482	NM_145698.5(ACBD5):c.51del (p.Cys18fs)	Pathogenic
2959386	NM_145698.5(ACBD5):c.1246C>T (p.Gln416Ter)	Pathogenic
3645713	NM_145698.5(ACBD5):c.1159C>T (p.Arg387Ter)	Pathogenic
3651701	NM_145698.5(ACBD5):c.1210dup (p.Arg404fs)	Pathogenic
3694654	NM_145698.5(ACBD5):c.70_73del (p.Arg24fs)	Pathogenic
58719	GRCh38/hg38 10p12.1-11.23(chr10:27046685-30228891)x1	Pathogenic
870223	NM_145698.4:c.626-689_937-234delins936+1075_c.936+1230inv	Pathogenic
915976	GRCh37/hg19 10p12.1(chr10:27504464-27504571)	Pathogenic
948162	NM_145698.5(ACBD5):c.667G>T (p.Glu223Ter)	Pathogenic
1475806	NM_145698.5(ACBD5):c.937-1del	Likely pathogenic
1910726	NM_145698.5(ACBD5):c.1405-2A>C	Likely pathogenic
1956406	NM_145698.5(ACBD5):c.303-2A>C	Likely pathogenic
1969898	NM_145698.5(ACBD5):c.181+1G>A	Likely pathogenic
2439623	NM_145698.5(ACBD5):c.462del (p.Ser155fs)	Likely pathogenic
2781413	NM_145698.5(ACBD5):c.829+1G>A	Likely pathogenic
2812262	NM_145698.5(ACBD5):c.491-2A>G	Likely pathogenic
3245040	NC_000010.10:g.(?27505835)(27506908_?)del	Likely pathogenic
3245042	NC_000010.10:g.(?27497155)(27497394_?)dup	Likely pathogenic
3367141	NM_145698.5(ACBD5):c.936+1G>A	Likely pathogenic
451186	NM_145698.5(ACBD5):c.1105A>T (p.Lys369Ter)	Likely pathogenic
968012	NM_145698.5(ACBD5):c.829+1_829+1074delinsCA	Likely pathogenic

SpliceAI

2902 predictions. Top by Δscore:

Variant	Effect	Δscore
10:27186377:A:G	acceptor_gain	1.0000
10:27197445:T:C	acceptor_gain	1.0000
10:27198525:AT:A	donor_gain	1.0000
10:27205192:TCTTA:T	donor_loss	1.0000
10:27205193:CTTA:C	donor_loss	1.0000
10:27205194:TTAC:T	donor_loss	1.0000
10:27205195:TACCT:T	donor_loss	1.0000
10:27205196:A:AC	donor_gain	1.0000
10:27205196:A:AT	donor_loss	1.0000
10:27205197:C:CC	donor_gain	1.0000
10:27205197:C:CG	donor_loss	1.0000
10:27208242:TTACC:T	donor_loss	1.0000
10:27208243:TACCT:T	donor_loss	1.0000
10:27208244:AC:A	donor_loss	1.0000
10:27208245:C:CT	donor_loss	1.0000
10:27208245:CCTG:C	donor_gain	1.0000
10:27208442:TGTC:T	acceptor_gain	1.0000
10:27208444:TC:T	acceptor_gain	1.0000
10:27208445:CCTA:C	acceptor_gain	1.0000
10:27208449:T:TC	acceptor_gain	1.0000
10:27208450:T:C	acceptor_gain	1.0000
10:27208451:T:C	acceptor_gain	1.0000
10:27208451:T:TC	acceptor_gain	1.0000
10:27210812:AC:A	donor_loss	1.0000
10:27210813:CC:C	donor_loss	1.0000
10:27210818:T:TA	donor_gain	1.0000
10:27211082:C:CC	acceptor_gain	1.0000
10:27215529:TTTTA:T	donor_loss	1.0000
10:27215530:TTTA:T	donor_loss	1.0000
10:27215531:TTA:T	donor_loss	1.0000

AlphaMissense

3500 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:27204492:A:G	W514R	0.999
10:27204492:A:T	W514R	0.999
10:27208310:A:G	L456P	0.999
10:27231813:A:G	W102R	0.999
10:27231813:A:T	W102R	0.999
10:27235094:T:A	K98N	0.999
10:27235094:T:G	K98N	0.999
10:27235160:C:A	K76N	0.999
10:27235160:C:G	K76N	0.999
10:27235182:A:G	L69P	0.999
10:27240359:A:C	F45L	0.999
10:27240359:A:T	F45L	0.999
10:27240361:A:G	F45L	0.999
10:27208277:A:G	L467P	0.998
10:27208319:A:G	L453P	0.998
10:27231768:A:G	Y117H	0.998
10:27231811:C:A	W102C	0.998
10:27231811:C:G	W102C	0.998
10:27231816:C:G	A101P	0.998
10:27235093:A:G	W99R	0.998
10:27235093:A:T	W99R	0.998
10:27235156:C:G	A78P	0.998
10:27235165:A:C	Y75D	0.998
10:27235176:A:G	F71S	0.998
10:27235205:G:C	F61L	0.998
10:27235205:G:T	F61L	0.998
10:27235207:A:G	F61L	0.998
10:27240351:G:T	A48D	0.998
10:27240360:A:G	F45S	0.998
10:27231764:A:T	V118D	0.997

dbSNP variants (sampled 300 via entrez): RS1000057271 (10:27182649 A>C), RS1000062740 (10:27185317 CCT>C), RS1000122321 (10:27219213 G>T), RS1000130985 (10:27189010 C>T), RS1000134291 (10:27209330 G>T), RS1000304983 (10:27238604 C>T), RS1000311759 (10:27232326 T>C,G), RS1000411715 (10:27216540 T>C), RS1000441831 (10:27238851 T>A,G), RS1000466004 (10:27187373 T>G), RS1000467477 (10:27210963 C>T), RS1000491913 (10:27195236 T>G), RS1000502482 (10:27229563 A>G), RS1000580669 (10:27231557 A>G), RS1000630058 (10:27203948 T>A)

Disease associations

OMIM: gene MIM:616618 | disease phenotypes: MIM:618863, MIM:608281, MIM:120970, MIM:188000

GenCC curated gene-disease

Disease	Classification	Inheritance
retinal dystrophy with leukodystrophy	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
acyl-CoA binding domain containing protein 5 deficiency	Definitive	AR

Mondo (7): retinal dystrophy with leukodystrophy (MONDO:0030026), retinal disorder (MONDO:0005283), scimitar anomaly, multiple cardiac malformations, and craniofacial and central nervous system abnormalities (MONDO:0012007), thrombocytopenia (MONDO:0002049), cone-rod dystrophy (MONDO:0015993), thrombocytopenia 2 (MONDO:0008555), inherited retinal dystrophy (MONDO:0019118)

Orphanet (3): Cone rod dystrophy (Orphanet:1872), Hereditary thrombocytopenia with normal platelets (Orphanet:268322), OBSOLETE: Inherited retinal disorder (Orphanet:71862)

HPO phenotypes

19 total (20 of 19 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000175	Cleft palate
HP:0000253	Progressive microcephaly
HP:0000510	Rod-cone dystrophy
HP:0000601	Hypotelorism
HP:0000750	Delayed speech and language development
HP:0001260	Dysarthria
HP:0001270	Motor delay
HP:0001310	Dysmetria
HP:0001488	Bilateral ptosis
HP:0001583	Rotary nystagmus
HP:0002515	Waddling gait
HP:0002527	Falls
HP:0003391	Gowers sign
HP:0003429	CNS hypomyelination
HP:0003701	Proximal muscle weakness
HP:0008167	Very long chain fatty acid accumulation
HP:0009904	Prominent ear helix
HP:0030147	Truncal titubation
HP:0000556	Retinal dystrophy

GWAS associations

0 associations (top):

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D000071700	Cone-Rod Dystrophies	C11.270.152; C11.768.585.658.250; C16.320.290.152
D012164	Retinal Diseases	C11.768
D058499	Retinal Dystrophies	C11.768.585.658
D013921	Thrombocytopenia	C15.378.140.855; C15.378.243.937
C564262	Scimitar Anomaly, Multiple Cardiac Malformations, and Craniofacial and Central Nervous System Abnormalities (supp.)
C536519	Thrombocytopenia chromosome breakage (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation	3
bisphenol F	increases expression, affects cotreatment, decreases expression	2
bisphenol S	increases expression, affects cotreatment, decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
methylmercuric chloride	increases expression	1
bisphenol A	increases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases abundance, increases expression	1
butyraldehyde	decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases expression, increases response to substance	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Leflunomide	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Ethanol	affects cotreatment, increases expression	1
Arsenic	increases abundance, increases expression	1
Vehicle Emissions	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Caffeine	decreases phosphorylation	1
Dexamethasone	decreases expression, affects cotreatment	1
Doxorubicin	decreases expression	1
Folic Acid	affects cotreatment, increases expression	1
Hydrogen Peroxide	affects expression	1
Indomethacin	affects cotreatment, decreases expression	1
Ivermectin	decreases expression	1
Lead	affects expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01955135	PHASE4	COMPLETED	Anesthesia for Retinopathy of Prematurity
NCT00039858	PHASE4	COMPLETED	Evaluation of Argatroban Injection in Pediatric Patients Requiring Anticoagulant Alternatives to Heparin
NCT00239733	PHASE4	TERMINATED	Anti-D for Treating Thrombocytopenia in Adults Infected With Hepatitis C Virus With or Without HIV Co-Infection
NCT00907478	PHASE4	COMPLETED	Study on Bone Marrow Morphology in Adults Receiving Romiplostim for Treatment of Thrombocytopenia Associated With Immune Thrombocytopenia Purpura (ITP)
NCT01727401	PHASE4	TERMINATED	Thromboprophylaxis of Venous Thromboembolism in Acutely-ill Medical Inpatients With Thrombocytopenia
NCT02032134	PHASE4	TERMINATED	Protocol for the Infusion of Buffy Coat-derived Cryopreserved Platelets in Patients With Severe Thrombocytopenia
NCT02267993	PHASE4	COMPLETED	Efficacy and Safety of rhTPO for the Treatment of Thrombocytopenia After Chemotherapy in AML Patients
NCT03633019	PHASE4	UNKNOWN	High-dose Use of rhTPO in CIT Patients
NCT03688191	PHASE4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04906083	PHASE4	UNKNOWN	Avatrombopag in Patients With End-stage Liver Disease and Thrombocytopenia
NCT05217719	PHASE4	UNKNOWN	Effects of Recombinant Human Thrombopoietin on Platelet Levels in ICU Patients
NCT05255003	PHASE4	RECRUITING	STrategies for Anticoagulation in Patients With thRombocytopenia and Cancer-associated Thrombosis
NCT05382013	PHASE4	UNKNOWN	Efficacy and Safety of Avatrombopag for Treating TCP in HBV-ACLF Patients Receiving ALSS Treatment
NCT05944458	PHASE4	COMPLETED	Efficacy of Intravenous N-Acetylcysteine in Preventing Linezolid-Induced Thrombocytopenia in Critically Ill Patients
NCT06562738	PHASE4	RECRUITING	Clinical Study on Efficacy and Safety of Hetrombopag in the Preoperative Patients of Thrombocytopenia
NCT00037791	PHASE3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00039910	PHASE3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00073580	PHASE3	COMPLETED	Angiomax in Patients With HIT/HITTS Type II Undergoing Off-Pump Coronary Artery Bypass Grafting (CABG) (CHOOSE)
NCT00102323	PHASE3	COMPLETED	AMG 531 Treatment of Thrombocytopenic Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) Refractory to Splenectomy
NCT00102336	PHASE3	COMPLETED	AMG 531 Treatment of Thrombocytopenic Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) Prior to Splenectomy
NCT00116688	PHASE3	COMPLETED	Open Label Extension Study of Romiplostim (AMG 531) in Thrombocytopenic Patients With Immune (Idiopathic) Thrombocytopenic Purpura (ITP)
NCT00128713	PHASE3	COMPLETED	Optimal Platelet Dose Strategy for Management of Thrombocytopenia
NCT00151866	PHASE3	COMPLETED	Efficacy of Transfusions With Platelets Stored in Platelet Additive Solution II Versus Plasma
NCT00261924	PHASE3	COMPLETED	Efficacy and Safety Study of Platelets Treated for Pathogen Inactivation and Stored for Up to Seven Days
NCT00415532	PHASE3	COMPLETED	Romiplostim (AMG 531) Versus Medical Standard of Care for Immune (Idiopathic) Thrombocytopenic Purpura
NCT00420914	PHASE3	TERMINATED	Strategies for Transfusion of Platelets (SToP)
NCT00501345	PHASE3	TERMINATED	Aspirin in Patients With Myocardial Infarction and Thrombocytopenia
NCT00508820	PHASE3	COMPLETED	An Open Label Study of Romiplostim in Adult Thrombocytopenic Subjects With ITP
NCT00678587	PHASE3	TERMINATED	Eltrombopag To Reduce The Need For Platelet Transfusion In Subjects With Chronic Liver Disease And Thrombocytopenia Undergoing Elective Invasive Procedures
NCT01438840	PHASE3	COMPLETED	Efficacy and Safety of Oral E5501 Plus Standard of Care for the Treatment of Thrombocytopenia in Adults With Chronic Immune Thrombocytopenia (Amendment 02)
NCT01444417	PHASE3	COMPLETED	Safety and Efficacy Study of Romiplostim to Treat Immune Thrombocytopenia (ITP) in Pediatric Patients
NCT01805648	PHASE3	UNKNOWN	Efficacy and Safety Study of Maintenance Treatment With rhTPO in Thrombocytopenic Subjects With ITP
NCT02244658	PHASE3	UNKNOWN	Recombinant Human Thrombopoietin (rhTPO) in Management of Chemotherapy-induced Thrombocytopenia in Acute Myelocytic Leukemia
NCT02389621	PHASE3	COMPLETED	Safety and Efficacy Study of Lusutrombopag for Thrombocytopenia in Patients With Chronic Liver Disease Undergoing Elective Invasive Procedures
NCT02444728	PHASE3	TERMINATED	Cyclophosphamide and Hydroxychloroquine for Thrombocytopenia in SLE
NCT02487563	PHASE3	COMPLETED	Prospective Study of Patients With Thrombocytopenia Following HSCT
NCT02578901	PHASE3	COMPLETED	American Trial Using Tranexamic Acid in Thrombocytopenia
NCT03326843	PHASE3	TERMINATED	Avatrombopag for the Treatment of Thrombocytopenia in Adults Scheduled for a Surgical Procedure
NCT03515096	PHASE3	COMPLETED	Eltrombopag vs. rhTPO to Increase Platelet Level After HSCT
NCT05563064	PHASE3	UNKNOWN	Effect of Herbal Formulation on Thrombocytes Count