ACADVL

Summary

ACADVL (acyl-CoA dehydrogenase very long chain, HGNC:92) is a protein-coding gene on chromosome 17p13.1, encoding Very long-chain acyl-CoA dehydrogenase, mitochondrial (P49748). Very long-chain specific acyl-CoA dehydrogenase is one of the acyl-CoA dehydrogenases that catalyze the first step of mitochondrial fatty acid beta-oxidation (FAO), breaking down fatty acids into acetyl-CoA and allowing the production of energy from fats.

The protein encoded by this gene is targeted to the inner mitochondrial membrane where it catalyzes the first step of the mitochondrial fatty acid beta-oxidation pathway. This acyl-Coenzyme A dehydrogenase is specific to long-chain and very-long-chain fatty acids. A deficiency in this gene product reduces myocardial fatty acid beta-oxidation and is associated with cardiomyopathy. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 37 — RefSeq curated summary.

At a glance

• Gene–disease (curated): very long chain acyl-CoA dehydrogenase deficiency (Definitive, ClinGen)
• GWAS associations: 2
• Clinical variants (ClinVar): 2,130 total — 146 pathogenic, 327 likely-pathogenic
• Phenotypes (HPO): 66
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_000018

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:92
Approved symbol	ACADVL
Name	acyl-CoA dehydrogenase very long chain
Location	17p13.1
Locus type	gene with protein product
Status	Approved
Aliases	VLCAD, LCACD, ACAD6
Ensembl gene	ENSG00000072778
Ensembl biotype	protein_coding
OMIM	609575
Entrez	37

Gene structure

Transcript identifiers

Ensembl transcripts: 83 — 52 protein_coding, 24 retained_intron, 4 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined

ENST00000322910, ENST00000350303, ENST00000356839, ENST00000542255, ENST00000543245, ENST00000577191, ENST00000577433, ENST00000577857, ENST00000578033, ENST00000578269, ENST00000578319, ENST00000578421, ENST00000578579, ENST00000578711, ENST00000578809, ENST00000578824, ENST00000579286, ENST00000579391, ENST00000579425, ENST00000579546, ENST00000579886, ENST00000579894, ENST00000580263, ENST00000580365, ENST00000581378, ENST00000581562, ENST00000582056, ENST00000582166, ENST00000582356, ENST00000582379, ENST00000582450, ENST00000583074, ENST00000583312, ENST00000583760, ENST00000583848, ENST00000583850, ENST00000583858, ENST00000584103, ENST00000585203, ENST00000883757, ENST00000883758, ENST00000883759, ENST00000883760, ENST00000883761, ENST00000883762, ENST00000883763, ENST00000883764, ENST00000883765, ENST00000883766, ENST00000883767, ENST00000883768, ENST00000883769, ENST00000883770, ENST00000883771, ENST00000916066, ENST00000916067, ENST00000916068, ENST00000916069, ENST00000916070, ENST00000916071, ENST00000945291, ENST00000945292, ENST00000945293, ENST00000945294, ENST00000945295, ENST00000945296, ENST00000945297, ENST00000945298, ENST00000945299, ENST00000945300, ENST00000945301, ENST00000945302, ENST00000945303, ENST00000945304, ENST00000945305, ENST00000945306, ENST00000945307, ENST00000945308, ENST00000945309, ENST00000945310, ENST00000945311, ENST00000945312, ENST00000945313

RefSeq mRNA: 4 — MANE Select: NM_000018 NM_000018, NM_001033859, NM_001270447, NM_001270448

CCDS: CCDS11090, CCDS42249, CCDS58509

Canonical transcript exons

ENST00000356839 — 20 exons

Exon	Start	End
ENSE00001486705	7219938	7220046
ENSE00003495192	7223813	7223875
ENSE00003496224	7221952	7222081
ENSE00003498077	7222177	7222302
ENSE00003511252	7224642	7224714
ENSE00003539847	7223644	7223730
ENSE00003579637	7224809	7224884
ENSE00003579906	7222667	7222865
ENSE00003587027	7223968	7224069
ENSE00003592784	7220604	7220676
ENSE00003600063	7224321	7224393
ENSE00003602696	7224957	7225266
ENSE00003623330	7221538	7221682
ENSE00003624965	7224480	7224552
ENSE00003626264	7223133	7223237
ENSE00003628984	7220122	7220197
ENSE00003650064	7224146	7224243
ENSE00003656333	7220464	7220529
ENSE00003678875	7220766	7220830
ENSE00003682500	7220924	7221058

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.87.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 98.8367 / max 1186.8631, expressed in 1827 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
159115	89.9945	1827
159114	4.9391	1098
159116	2.5998	1202
159117	0.8662	336
208045	0.3237	132
159118	0.1134	48

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland cortex	UBERON:0035827	99.87	gold quality
apex of heart	UBERON:0002098	99.86	gold quality
right adrenal gland	UBERON:0001233	99.85	gold quality
left adrenal gland cortex	UBERON:0035825	99.84	gold quality
left adrenal gland	UBERON:0001234	99.83	gold quality
adenohypophysis	UBERON:0002196	99.83	gold quality
right lobe of liver	UBERON:0001114	99.81	gold quality
adrenal cortex	UBERON:0001235	99.81	gold quality
metanephros cortex	UBERON:0010533	99.81	gold quality
lower esophagus mucosa	UBERON:0035834	99.79	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.78	gold quality
left lobe of thyroid gland	UBERON:0001120	99.77	gold quality
right lobe of thyroid gland	UBERON:0001119	99.74	gold quality
adrenal gland	UBERON:0002369	99.73	gold quality
pituitary gland	UBERON:0000007	99.68	gold quality
heart left ventricle	UBERON:0002084	99.68	gold quality
cerebellar hemisphere	UBERON:0002245	99.68	gold quality
small intestine Peyer’s patch	UBERON:0003454	99.68	gold quality
mucosa of transverse colon	UBERON:0004991	99.68	gold quality
body of pancreas	UBERON:0001150	99.67	gold quality
transverse colon	UBERON:0001157	99.67	gold quality
body of stomach	UBERON:0001161	99.66	gold quality
right uterine tube	UBERON:0001302	99.66	gold quality
cardiac ventricle	UBERON:0002082	99.66	gold quality
right testis	UBERON:0004534	99.64	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.63	gold quality
left testis	UBERON:0004533	99.63	gold quality
cerebellar cortex	UBERON:0002129	99.62	gold quality
right atrium auricular region	UBERON:0006631	99.62	gold quality
endocervix	UBERON:0000458	99.61	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	118.47
E-HCAD-4	yes	40.77
E-MTAB-6075	no	696.30
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TFAP2A

miRNA regulators (miRDB)

21 targeting ACADVL, 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-302E	99.96	70.74	2669
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699
HSA-MIR-520D-3P	99.83	70.78	1676
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-4512	95.26	63.08	371
HSA-MIR-4737	89.94	65.03	82

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 36)

• coiled-coil motif bypasses chaperone and is a critical factor in the folding of gp37 (PMID:15576786)
• A new a unique mutation (IVS13+25G>A) is reported in a compound heterozygote carrying the 1748 C>T mutation in exon 18. (PMID:16464760)
• the bacterial expression system developed here will significantly advance our understanding of both the clinical aspects of VLCAD deficiency and the basic biochemistry of the enzyme (PMID:17374501)
• In asymptomatic mild VLCADdeficiency, a fat-reduced diet may not be necessary, whereas in later infancy and adolescence, strenuous physical exercise may require additional energy from medium-chain fat. (PMID:17457695)
• Report the course of disease in a pair of monozygotic twin sisters. (PMID:17514507)
• Bezafibrate, a widely prescribed hypolipidemic drug, cn be used for the correction of VLCAD deficiency and exemplifies the integration of molecular information in a therapeutic strategy (PMID:17999356)
• Loss of heterozygosity on 17p13 and down-regulation of ACADVL can be used to discriminate adrenal cortex neoplasms from adrenocortical adenoma. (PMID:18156936)
• This study confirms that VLCAD deficiency, although being less frequent than CPT II deficiency, should be systematically considered in the differential diagnosis of exercise-induced rhabdomyolysis. (PMID:19327992)
• Results suggest a novel regulatory mechanism for homeostatic VLCAD activity, whose dysregulation might be involved in the production of oxidative stress and in the pathogenesis of idiopathic pulmonary fibrosis. (PMID:19889959)
• Missense mutations in Very-Long-Chain Acyl-CoA Dehydrogenase is associated with inborn errors of lipid metabolism. (PMID:20060901)
• Down regulation of ACADVL is associated with cervical squamous cell carcinoma. (PMID:20099975)
• Case Report: missense mutation within the ACADVL gene responsible for very-long-chain acyl-CoA dehydrogenase deficiency and sudden infant death. (PMID:20107901)
• Analyzed potential rhabdomyolysis-susceptibility genes (RYR 1, CPT II, VLCAD and CYP 2D6) from autopsy samples of methamphetamine abusers; no obvious relationship between the genetic mutations observed in this study and rhabdomyolysis was seen. (PMID:20952238)
• Identification of 2 VLCAD mutations leads to precautions in the management of the children with VLCAD deficiency. (PMID:21932095)
• The expressions of LCHAD gene and protein are remarkably reduced in early onset severe preeclampsia and HELLP syndrome. (PMID:22093928)
• These findings support the importance of considering that mutations may be present in the ACADVL gene when a significant partial deficiency is found in CPTII activity, but no mutations in the CPT2 gene can be identified. (PMID:23169530)
• These results emphasize the importance of functional investigation of abnormal NBS or clinical testing suggestive but not diagnostic of very-long-chain acyl-CoA dehydrogenase . (PMID:23480858)
• 11 mutations in ACADVL gene in 7 patients, 7 reported (p.S22X, p.W427X, p.A213T, p.G222R, p.R450H, c.296-297delCA, c.1605+1G>T), 4 novel (p.S72F, p.Q100X, p.M437T, p.D466Y). p.R450H and p.D466Y (14.28%, 2/14 alleles) mutations identified in 2 alleles. (PMID:24801231)
• following variants should be considered likely pathogenic c.1273G > A (p.A425T), c.1001T > G (p.M334R), c.538G > A (p.A180T), c.640T > G (p.F214V), c.1076C > T (p.A359V), c.1019G > T (p.G340V), c.889_891delGAG (p.E297del), and c.1103A > C (p.Q368P); patients homozygous for the most common pathogenic variant, c.848T > C (p.V283A) can be expected to have a more benign clinical course (PMID:26385305)
• We retrospectively analyzed early outcomes for individuals who were diagnosed with VLCAD deficiency by NBS and describe initial presentations, diagnosis, clinical outcomes and treatment in a cohort of 52 individuals ages 1-18year. (PMID:27209629)
• There are currently no biochemical markers for prediction of disease severity and for the need for treatment in VLCAD deficiency. Mutation analysis may offer predictive value but this may not be robust enough for a large proportion of those mutations that have not been previously reported in clinically affected patients. (PMID:27246109)
• LCHAD and MCAD are differentially expressed in maternal and fetal tissues during normal late pregnancy, which may represent a metabolic adaptation in response to physiological maternal dyslipidemia during late pregnancy. (PMID:27871288)
• The authors provide novel insights into the cellular energy household of cells from HADHA/ACADVL patients and demonstrate for the first time a connection between fatty acid metabolism, mitochondrial morphology and reactive oxygen species in patients with these rare genetic disorders. (PMID:29459657)
• Sequencing of the ACADVL gene revealed that all individuals with activities below 24% were true Very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) patients, individuals with residual activities between 24 and 27% carried either one or two mutations. Twenty new mutations could be identified and functionally classified based on their effect on enzyme function. (PMID:30194637)
• homozygous mutation in ACADVL associated with pediatric familial dilated cardiomyopathy (PMID:30840296)
• VLCADD is relatively rare in southern China, for which late-onset form is common (PMID:30950014)
• One potential hotspot ACADVL mutation in Chinese patients with very-long-chain acyl-coenzyme A dehydrogenase deficiency. (PMID:31794763)
• Mitochondrial energetic impairment in a patient with late-onset glutaric acidemia Type 2. (PMID:32804429)
• Novel ACADVL variants resulting in mitochondrial defects in long-chain acyl-CoA dehydrogenase deficiency. (PMID:33150772)
• Screening and follow-up results of fatty acid oxidative metabolism disorders in 608 818 newborns in Jining, Shandong province. (PMID:34704412)
• VLCAD inhibits the proliferation and invasion of hepatocellular cancer cells through regulating PI3K/AKT axis. (PMID:35001339)
• Characterization of exonic variants of uncertain significance in very long-chain acyl-CoA dehydrogenase identified through newborn screening. (PMID:35218577)
• Structural basis for defective membrane targeting of mutant enzyme in human VLCAD deficiency. (PMID:35760926)
• Treatment of VLCAD-Deficient Patient Fibroblasts with Peroxisome Proliferator-Activated Receptor delta Agonist Improves Cellular Bioenergetics. (PMID:36078043)
• Hypermethylation of ACADVL is involved in the high-intensity interval training-associated reduction of cardiac fibrosis in heart failure patients. (PMID:36894992)
• Specifications of the ACMG/AMP guidelines for ACADVL variant interpretation. (PMID:37549443)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	acadvl	ENSDARG00000016687
mus_musculus	Acadvl	ENSMUSG00000018574
rattus_norvegicus	Acadvl	ENSRNOG00000018114
drosophila_melanogaster	Acadvl	FBGN0034432
caenorhabditis_elegans		WBGENE00017125

Paralogs (14): ACOX3 (ENSG00000087008), GCDH (ENSG00000105607), ACAD10 (ENSG00000111271), ACADL (ENSG00000115361), ACADM (ENSG00000117054), ACADS (ENSG00000122971), IVD (ENSG00000128928), ACAD8 (ENSG00000151498), ACOXL (ENSG00000153093), ACOX1 (ENSG00000161533), ACOX2 (ENSG00000168306), ACAD9 (ENSG00000177646), ACADSB (ENSG00000196177), ACAD11 (ENSG00000240303)

Protein

Protein identifiers

Very long-chain acyl-CoA dehydrogenase, mitochondrial — P49748 (reviewed: P49748)

Alternative names: Long-chain acyl-CoA dehydrogenase, mitochondrial

All UniProt accessions (10): P49748, G3V1M7, J3KS89, J3KSR4, J3QKU9, J3QRJ8, J9JID6, K7EJW8, K7EMF8, K7EQP4

UniProt curated annotations — full annotation on UniProt →

Function. Very long-chain specific acyl-CoA dehydrogenase is one of the acyl-CoA dehydrogenases that catalyze the first step of mitochondrial fatty acid beta-oxidation (FAO), breaking down fatty acids into acetyl-CoA and allowing the production of energy from fats. The first step of FAO consists in the proR-proR stereospecific alpha, beta-dehydrogenation of fatty acyl-CoA thioesters using the electron transfer flavoprotein (ETF) as their physiologic electron acceptor, resulting in the formation of trans-2-enoyl-CoA ((2E)-enoyl-CoA). Among the different mitochondrial acyl-CoA dehydrogenases, very long-chain specific acyl-CoA dehydrogenase acts specifically on fatty acyl-CoAs with saturated 12 to 24 carbons long primary chains.

Subunit / interactions. Homodimer. Homodimerizes after import into the mitochondrion.

Subcellular location. Mitochondrion inner membrane Mitochondrion inner membrane.

Tissue specificity. Predominantly expressed in heart and skeletal muscle (at both mRNA and protein levels). Also detected in kidney and liver (at protein level).

Post-translational modifications. S-nitrosylation at Cys-237 in liver improves catalytic efficiency.

Disease relevance. Acyl-CoA dehydrogenase very long-chain deficiency (ACADVLD) [MIM:201475] An inborn error of mitochondrial fatty acid beta-oxidation which leads to impaired long-chain fatty acid beta-oxidation. It is clinically heterogeneous, with three major phenotypes: a severe childhood form characterized by early onset, high mortality and high incidence of cardiomyopathy; a milder childhood form with later onset, characterized by hypoketotic hypoglycemia, low mortality and rare cardiomyopathy; an adult form, with isolated skeletal muscle involvement, rhabdomyolysis and myoglobinuria, usually triggered by exercise or fasting. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Lipid metabolism; mitochondrial fatty acid beta-oxidation.

Similarity. Belongs to the acyl-CoA dehydrogenase family.

Isoforms (3)

UniProt ID	Names	Canonical?
P49748-1	1	yes
P49748-2	2, DeltaEx3 VLCAD
P49748-3	3

RefSeq proteins (4): NP_000009, NP_001029031, NP_001257376, NP_001257377 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006089	Acyl-CoA_DH_CS	Conserved_site
IPR006091	AcylCoA_DH/ox_M	Domain
IPR009075	AcylCo_DH/oxidase_C	Domain
IPR009100	AcylCoA_DH/oxidase_NM_dom_sf	Homologous_superfamily
IPR013786	AcylCoA_DH/ox_N	Domain
IPR036250	AcylCo_DH-like_C	Homologous_superfamily
IPR037069	AcylCoA_DH/ox_N_sf	Homologous_superfamily
IPR046373	Acyl-CoA_Oxase/DH_mid-dom_sf	Homologous_superfamily
IPR049448	ACAD9/ACADV-like_C	Domain

Pfam: PF00441, PF02770, PF02771, PF21343

Enzyme classification (BRENDA):

• EC 1.3.8.8 — long-chain acyl-CoA dehydrogenase (BRENDA: 10 organisms, 91 substrates, 24 inhibitors, 53 Km, 6 kcat entries)
• EC 1.3.8.9 — very-long-chain acyl-CoA dehydrogenase (BRENDA: 3 organisms, 4 substrates, 0 inhibitors, 0 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

19 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
PALMITOYL-COA	0.0009–0.78	8
DECANOYL-COA	0.0022–0.13	5
DODECANOYL-COA	0.0015–0.2	5
OCTANOYL-COA	0.0033–0.23	5
STEAROYL-COA	0.0037–0.29	5
TETRADECANOYL-COA	0.0023–0.38	5
ELECTRON-TRANSFER FLAVOPROTEIN	0.0008–0.012	4
HEXANOYL-COA	0.0063–0.55	3
FAD	0.0014–0.0025	2
PHENAZINE METHOSULFATE	1–1.1	2
4-CIS,7-CIS-DECADIENOYL-COA	0.32	1
4-CIS-DECENOYL-COA	0.25	1
5-CIS-DECENOYL-COA	0.2	1
6-CIS-DECENOYL-COA	0.32	1
CIS,CIS,CIS,CIS-4,7,10,13-HEXADECATETRAENOYL-COA	0.24	1

Catalyzed reactions (Rhea), 11 shown:

• a long-chain 2,3-saturated fatty acyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = a long-chain (2E)-enoyl-CoA + reduced [electron-transfer flavoprotein] (RHEA:17721)
• a very-long-chain 2,3-saturated fatty acyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = a very-long-chain (2E)-enoyl-CoA + reduced [electron-transfer flavoprotein] (RHEA:19181)
• oxidized [electron-transfer flavoprotein] + hexadecanoyl-CoA + H(+) = (2E)-hexadecenoyl-CoA + reduced [electron-transfer flavoprotein] (RHEA:43448)
• docosanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-docosenoyl-CoA + reduced [electron-transfer flavoprotein] (RHEA:47228)
• tetracosanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-tetracosenoyl-CoA + reduced [electron-transfer flavoprotein] (RHEA:47232)
• eicosanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-eicosenoyl-CoA + reduced [electron-transfer flavoprotein] (RHEA:47236)
• octadecanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-octadecenoyl-CoA + reduced [electron-transfer flavoprotein] (RHEA:47240)
• dodecanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-dodecenoyl-CoA + reduced [electron-transfer flavoprotein] (RHEA:47296)
• oxidized [electron-transfer flavoprotein] + (9Z)-octadecenoyl-CoA + H(+) = (2E,9Z)-octadecadienoyl-CoA + reduced [electron-transfer flavoprotein] (RHEA:47300)
• (9Z)-hexadecenoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E,9Z)-hexadecadienoyl-CoA + reduced [electron-transfer flavoprotein] (RHEA:47304)
• tetradecanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-tetradecenoyl-CoA + reduced [electron-transfer flavoprotein] (RHEA:47316)

UniProt features (135 total): sequence variant 47, helix 26, modified residue 23, strand 10, turn 7, mutagenesis site 6, binding site 5, region of interest 3, sequence conflict 3, splice variant 2, transit peptide 1, chain 1, active site 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7S7G	X-RAY DIFFRACTION	1.34
2UXW	X-RAY DIFFRACTION	1.45
3B96	X-RAY DIFFRACTION	1.91

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49748-F1	90.65	0.85

Functional residue map

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

Catalytic / active sites (1): 462 (proton acceptor)

Ligand- & substrate-binding residues (5): 562; 214–223; 249–251; 461–463; 464–466

Post-translational modifications (23): 51, 71, 71, 195, 237, 239, 239, 276, 276, 278, 278, 298, 331, 331, 372, 482, 482, 517, 522, 550 …

Mutagenesis-validated functional residues (6):

Position	Phenotype
458	decreased acyl-coa dehydrogenase activity. decreased affinity for acyl-coa. no effect on fad cofactor-binding.
458	loss of acyl-coa dehydrogenase activity. loss of fad cofactor-binding.
458	decreased acyl-coa dehydrogenase activity. no effect on affinity for acyl-coa. decreased fad cofactor-binding.
462	decreased acyl-coa dehydrogenase activity. no effect on affinity for acyl-coa. no effect on fad cofactor-binding.
462	loss of acyl-coa dehydrogenase activity. no effect on fad cofactor-binding.
490	changed substrate specificity with decreased affinity for tetradecanoyl-coa and hexadecanoyl-coa.

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-381038	XBP1(S) activates chaperone genes
R-HSA-77305	Beta oxidation of palmitoyl-CoA to myristoyl-CoA
R-HSA-1430728	Metabolism
R-HSA-2262752	Cellular responses to stress
R-HSA-381070	IRE1alpha activates chaperones
R-HSA-381119	Unfolded Protein Response (UPR)
R-HSA-556833	Metabolism of lipids
R-HSA-77286	mitochondrial fatty acid beta-oxidation of saturated fatty acids
R-HSA-77289	Mitochondrial Fatty Acid Beta-Oxidation
R-HSA-8953897	Cellular responses to stimuli
R-HSA-8978868	Fatty acid metabolism

MSigDB gene sets: 398 (showing top): GOBP_LIPID_MODIFICATION, MODULE_93, GOBP_FATTY_ACID_CATABOLIC_PROCESS, GOBP_EPITHELIUM_DEVELOPMENT, REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR, GOBP_RESPONSE_TO_COLD, PID_HNF3B_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_LIPID_METABOLIC_PROCESS, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_THE_CH_CH_GROUP_OF_DONORS, ENK_UV_RESPONSE_KERATINOCYTE_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_NEGATIVE_REGULATION_OF_LIPID_BIOSYNTHETIC_PROCESS, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, LUCAS_HNF4A_TARGETS_UP, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS

GO Biological Process (13): temperature homeostasis (GO:0001659), response to cold (GO:0009409), energy derivation by oxidation of organic compounds (GO:0015980), epithelial cell differentiation (GO:0030855), fatty acid beta-oxidation using acyl-CoA dehydrogenase (GO:0033539), negative regulation of fatty acid biosynthetic process (GO:0045717), negative regulation of fatty acid oxidation (GO:0046322), regulation of cholesterol metabolic process (GO:0090181), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631), fatty acid beta-oxidation (GO:0006635), fatty acid catabolic process (GO:0009062), carboxylic acid metabolic process (GO:0019752)

GO Molecular Function (9): fatty-acyl-CoA binding (GO:0000062), acyl-CoA dehydrogenase activity (GO:0003995), long-chain fatty acyl-CoA dehydrogenase activity (GO:0004466), very-long-chain fatty acyl-CoA dehydrogenase activity (GO:0017099), identical protein binding (GO:0042802), flavin adenine dinucleotide binding (GO:0050660), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on the CH-CH group of donors (GO:0016627)

GO Cellular Component (8): nucleoplasm (GO:0005654), nucleolus (GO:0005730), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial matrix (GO:0005759), mitochondrial membrane (GO:0031966), mitochondrial nucleoid (GO:0042645), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
IRE1alpha activates chaperones	1
mitochondrial fatty acid beta-oxidation of saturated fatty acids	1
Cellular responses to stimuli	1
Unfolded Protein Response (UPR)	1
Cellular responses to stress	1
Metabolism	1
Mitochondrial Fatty Acid Beta-Oxidation	1
Fatty acid metabolism	1
Metabolism of lipids	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
acyl-CoA dehydrogenase activity	3
mitochondrion	3
negative regulation of fatty acid metabolic process	2
fatty acid oxidation	2
nuclear lumen	2
cellular anatomical structure	2
intracellular membraneless organelle	2
multicellular organismal-level homeostasis	1
response to stress	1
response to temperature stimulus	1
generation of precursor metabolites and energy	1
cell differentiation	1
epithelium development	1
fatty acid beta-oxidation	1
fatty acid biosynthetic process	1
regulation of fatty acid biosynthetic process	1
negative regulation of lipid biosynthetic process	1
regulation of fatty acid oxidation	1
cholesterol metabolic process	1
regulation of steroid metabolic process	1
regulation of small molecule metabolic process	1
primary metabolic process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
fatty acid catabolic process	1
fatty acid ligase activity	1
fatty acid metabolic process	1
lipid catabolic process	1
monocarboxylic acid catabolic process	1
oxoacid metabolic process	1
acyl-CoA binding	1
fatty acid derivative binding	1
oxidoreductase activity, acting on the CH-CH group of donors, with a flavin as acceptor	1
protein binding	1
nucleotide binding	1
anion binding	1
binding	1
catalytic activity	1
oxidoreductase activity	1
cytoplasm	1

Protein interactions and networks

STRING

2716 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACADVL	CPT2	P23786	935
ACADVL	HADHA	P40939	917
ACADVL	ACSL1	P33121	779
ACADVL	HADHB	P55084	763
ACADVL	HADH	Q16836	734
ACADVL	SLC25A20	O43772	716
ACADVL	CPT1A	P50416	700
ACADVL	ACOX1	Q15067	699
ACADVL	FASN	P49327	697
ACADVL	ACAA2	P42765	694
ACADVL	ETFDH	Q16134	690
ACADVL	PLIN2	Q99541	669
ACADVL	ECHS1	P30084	656
ACADVL	CPT1B	Q92523	646
ACADVL	EHHADH	Q08426	627
ACADVL	PPARA	Q07869	627

IntAct

80 interactions, top by confidence:

A	B	Type	Score
SEC23B	SEC24D	psi-mi:“MI:0914”(association)	0.920
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
NDUFA13	NDUFS8	psi-mi:“MI:0914”(association)	0.640
SINHCAF	TNRC18	psi-mi:“MI:0914”(association)	0.640
TAF1B	ACADVL	psi-mi:“MI:0915”(physical association)	0.560
ACADVL	TAF1B	psi-mi:“MI:0915”(physical association)	0.560
NPPA	A2ML1	psi-mi:“MI:0914”(association)	0.530
FTH1	A2ML1	psi-mi:“MI:0914”(association)	0.530
ECSIT	NDUFS8	psi-mi:“MI:0914”(association)	0.530
ACADVL	APC	psi-mi:“MI:0914”(association)	0.530
SGSM1	CETN2	psi-mi:“MI:0914”(association)	0.530
TRAT1	ACADVL	psi-mi:“MI:0914”(association)	0.530
CDH1	ACTN4	psi-mi:“MI:0915”(physical association)	0.500
GNL3	IPO5	psi-mi:“MI:0914”(association)	0.480
SURF1	ACADVL	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
ACADVL	RPSA	psi-mi:“MI:0915”(physical association)	0.370
GPHN	ACADVL	psi-mi:“MI:0915”(physical association)	0.370
SIRT4	VWA8	psi-mi:“MI:0914”(association)	0.350
CKAP5	TACC3	psi-mi:“MI:0914”(association)	0.350
Ncbp2	ZC3H18	psi-mi:“MI:0914”(association)	0.350
KIF2A	EIF3F	psi-mi:“MI:0914”(association)	0.350
FASTKD3	VWA8	psi-mi:“MI:0914”(association)	0.350
CD177	MYO1G	psi-mi:“MI:0914”(association)	0.350
NMES1	NDUFS8	psi-mi:“MI:0914”(association)	0.350
COQ9	NDUFS8	psi-mi:“MI:0914”(association)	0.350

BioGRID (192): ACADVL (Affinity Capture-MS), ACADVL (Affinity Capture-MS), ACADVL (Affinity Capture-MS), ACADVL (Affinity Capture-MS), ACADVL (Affinity Capture-MS), ACADVL (Affinity Capture-MS), ACADVL (Affinity Capture-MS), ACADVL (Affinity Capture-MS), ACADVL (Affinity Capture-MS), ACADVL (Affinity Capture-MS), ACADVL (Affinity Capture-MS), ACADVL (Affinity Capture-MS), ACADVL (Affinity Capture-MS), ACADVL (Affinity Capture-MS), ACADVL (Affinity Capture-MS)

ESM2 similar proteins: B1WC61, B3DMA2, O32176, O64894, O65201, P07872, P12007, P15650, P26440, P28330, P45953, P45954, P48818, P49748, P50544, P51174, P70584, P79273, P79274, Q0NXR6, Q15067, Q3SZI8, Q3SZP5, Q47146, Q54IM8, Q54RR5, Q5EAD4, Q5R778, Q5RBD5, Q5RC19, Q5RF40, Q5ZHT1, Q60HI0, Q64428, Q6JQN1, Q709F0, Q80XL6, Q8HXY7, Q8JZN5, Q8X7R2

Diamond homologs: A5A6I0, A8WP91, A8XNF0, B1WC61, B9U6P5, C3UVB0, D3JV03, F8GVD3, G3KIM8, H6LGM6, I6Y3V5, J7TF92, K4L7X3, O32176, O34421, O54143, P08503, P0A9U8, P0A9U9, P0A9V0, P11310, P12007, P15650, P15651, P16219, P26440, P28330, P41367, P45857, P45867, P45952, P45953, P45954, P46703, P48818, P49748, P50544, P51174, P52042, P63428

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
ACADVL	“down-regulates quantity”	palmitoyl-CoA(4-)	“chemical modification”
ACADVL	“down-regulates quantity”	FAD(3-)	“chemical modification”
ACADVL	“up-regulates quantity”	(E)-hexadec-2-enoyl-CoA(4-)	“chemical modification”
ACADVL	“up-regulates quantity”	FADH2(2-)	“chemical modification”
PRKACA	“up-regulates activity”	ACADVL	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

2130 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	146
Likely pathogenic	327
Uncertain significance	640
Likely benign	786
Benign	37

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1036078	NM_000018.4(ACADVL):c.1909_1912dup (p.Ser638fs)	Pathogenic
1073342	NM_000018.4(ACADVL):c.642_643del (p.Phe214fs)	Pathogenic
1391720	NM_000018.4(ACADVL):c.1138C>T (p.Gln380Ter)	Pathogenic
1392500	NM_000018.4(ACADVL):c.1093_1094insT (p.Asn365fs)	Pathogenic
1427529	NM_000018.4(ACADVL):c.277+2T>C	Pathogenic
1427626	NM_000018.4(ACADVL):c.1605+1G>C	Pathogenic
1437138	NM_000018.4(ACADVL):c.747G>A (p.Trp249Ter)	Pathogenic
1440456	NM_000018.4(ACADVL):c.100_104dup (p.Arg37fs)	Pathogenic
1442492	NM_000018.4(ACADVL):c.1138dup (p.Gln380fs)	Pathogenic
1447373	NM_000018.4(ACADVL):c.488dup (p.Leu163fs)	Pathogenic
1452475	NM_000018.4(ACADVL):c.1389del (p.Thr464fs)	Pathogenic
1454349	NM_000018.4(ACADVL):c.1151_1154dup (p.Met386fs)	Pathogenic
1454452	NM_000018.4(ACADVL):c.655C>A (p.Pro219Thr)	Pathogenic
145484	GRCh38/hg38 17p13.2-12(chr17:5732953-12095349)x3	Pathogenic
1455065	NM_000018.4(ACADVL):c.1587G>T (p.Leu529Phe)	Pathogenic
1455427	NM_000018.4(ACADVL):c.303del (p.Glu104fs)	Pathogenic
1457909	NM_000018.4(ACADVL):c.1739_1751del (p.Val580fs)	Pathogenic
1458252	NM_000018.4(ACADVL):c.465_466dup (p.Cys156fs)	Pathogenic
1458622	NM_000018.4(ACADVL):c.437T>G (p.Val146Gly)	Pathogenic
1460064	NM_000018.4(ACADVL):c.1605+1G>T	Pathogenic
1484294	NM_000018.4(ACADVL):c.1316G>C (p.Gly439Ala)	Pathogenic
1621	NM_000018.4(ACADVL):c.1080_1182+2del	Pathogenic
1624	NM_000018.4(ACADVL):c.343del	Pathogenic
1626	NM_000018.4(ACADVL):c.385GAG[1] (p.Glu130del)	Pathogenic
1685495	NM_000018.4(ACADVL):c.1292A>G (p.Asp431Gly)	Pathogenic
1685496	NM_000018.4(ACADVL):c.1752-1G>A	Pathogenic
1699014	NM_000018.4(ACADVL):c.552C>A (p.Ile184=)	Pathogenic
1707706	NM_000018.4(ACADVL):c.103_112dup (p.Arg38fs)	Pathogenic
1707707	NM_000018.4(ACADVL):c.277+1G>A	Pathogenic
1707708	NM_000018.4(ACADVL):c.1077+2T>A	Pathogenic

SpliceAI

3019 predictions. Top by Δscore:

Variant	Effect	Δscore
17:7220463:GCT:G	acceptor_gain	1.0000
17:7220756:C:G	acceptor_gain	1.0000
17:7220761:T:TA	acceptor_gain	1.0000
17:7220761:TGCAG:T	acceptor_loss	1.0000
17:7220762:GCA:G	acceptor_loss	1.0000
17:7220763:CAG:C	acceptor_loss	1.0000
17:7220764:A:AG	acceptor_gain	1.0000
17:7220764:AGT:A	acceptor_gain	1.0000
17:7220765:G:GA	acceptor_gain	1.0000
17:7220765:GT:G	acceptor_gain	1.0000
17:7220765:GTG:G	acceptor_gain	1.0000
17:7220765:GTGC:G	acceptor_gain	1.0000
17:7220765:GTGCT:G	acceptor_gain	1.0000
17:7220831:G:GG	donor_gain	1.0000
17:7220831:GTA:G	donor_loss	1.0000
17:7220832:T:G	donor_loss	1.0000
17:7220923:GGAA:G	acceptor_gain	1.0000
17:7221019:GCCC:G	donor_gain	1.0000
17:7221024:G:GG	donor_gain	1.0000
17:7221536:A:AG	acceptor_gain	1.0000
17:7221537:G:GG	acceptor_gain	1.0000
17:7222063:G:GT	donor_gain	1.0000
17:7222175:A:AG	acceptor_gain	1.0000
17:7222176:G:GG	acceptor_gain	1.0000
17:7222176:GTA:G	acceptor_gain	1.0000
17:7222176:GTAAT:G	acceptor_gain	1.0000
17:7222299:CCCA:C	donor_gain	1.0000
17:7222300:CCA:C	donor_gain	1.0000
17:7222301:CA:C	donor_gain	1.0000
17:7222301:CAGT:C	donor_loss	1.0000

AlphaMissense

4263 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:7221614:G:A	G185D	0.999
17:7221969:T:C	F214L	0.999
17:7221971:C:A	F214L	0.999
17:7221971:C:G	F214L	0.999
17:7221974:T:G	C215W	0.999
17:7221976:T:C	L216P	0.999
17:7222786:C:A	A333D	0.999
17:7222798:T:A	L337H	0.999
17:7222798:T:C	L337P	0.999
17:7222810:G:T	R341M	0.999
17:7223713:A:C	S418R	0.999
17:7223715:C:A	S418R	0.999
17:7223715:C:G	S418R	0.999
17:7223717:A:T	K419I	0.999
17:7223718:A:C	K419N	0.999
17:7223718:A:T	K419N	0.999
17:7224022:G:A	G463R	0.999
17:7224022:G:C	G463R	0.999
17:7224022:G:T	G463W	0.999
17:7224030:T:A	N465K	0.999
17:7224030:T:G	N465K	0.999
17:7221607:A:C	S183R	0.998
17:7221609:C:A	S183R	0.998
17:7221609:C:G	S183R	0.998
17:7221622:G:C	G188R	0.998
17:7221964:C:A	A212D	0.998
17:7221972:T:C	C215R	0.998
17:7221973:G:A	C215Y	0.998
17:7222063:G:A	G245E	0.998
17:7222070:G:C	K247N	0.998

dbSNP variants (sampled 300 via entrez): RS1000495978 (17:7221016 A>C,G), RS1000852748 (17:7224909 A>C), RS1001019087 (17:7217766 AGGCAAACATGGAGACCT>A), RS1001027299 (17:7219801 G>A,C), RS1001101895 (17:7219797 C>A,G), RS1001412868 (17:7220984 G>T), RS1001450141 (17:7219617 C>G), RS1001479462 (17:7219959 C>G,T), RS1001801210 (17:7216107 C>A), RS1001853867 (17:7216428 T>C), RS1002550581 (17:7222438 T>A,C), RS1003440269 (17:7216599 C>T), RS1003472016 (17:7217905 G>A,T), RS1003492592 (17:7222131 C>T), RS1003557539 (17:7221286 T>C)

Disease associations

OMIM: gene MIM:609575 | disease phenotypes: MIM:201475, MIM:600001, MIM:192600, MIM:618793, MIM:151623, MIM:609266, MIM:607594, MIM:557000

GenCC curated gene-disease

Disease	Classification	Inheritance
very long chain acyl-CoA dehydrogenase deficiency	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
very long chain acyl-CoA dehydrogenase deficiency	Definitive	AR

Mondo (12): very long chain acyl-CoA dehydrogenase deficiency (MONDO:0008723), pancreatic hypoplasia-diabetes-congenital heart disease syndrome (MONDO:0010802), dilated cardiomyopathy (MONDO:0005021), familial hypertrophic cardiomyopathy (MONDO:0024573), intellectual developmental disorder 62 (MONDO:0032919), myopathy (MONDO:0005336), breast ductal adenocarcinoma (MONDO:0005590), Li-Fraumeni syndrome (MONDO:0018875), common variable immunodeficiency (MONDO:0015517), cardiac rhythm disease (MONDO:0007263), Pearson syndrome (MONDO:0010797), autism spectrum disorder (MONDO:0005258)

Orphanet (9): Very long chain acyl-CoA dehydrogenase deficiency (Orphanet:26793), Pancreatic hypoplasia-diabetes-congenital heart disease syndrome (Orphanet:2255), Dilated cardiomyopathy (Orphanet:217604), Rare familial disorder with hypertrophic cardiomyopathy (Orphanet:99739), Li-Fraumeni syndrome (Orphanet:524), OBSOLETE: Common variable immunodeficiency (Orphanet:1572), Pearson syndrome (Orphanet:699), NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy (Orphanet:155), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

66 total (30 of 66 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000952	Jaundice
HP:0001252	Hypotonia
HP:0001254	Lethargy
HP:0001324	Muscle weakness
HP:0001397	Hepatic steatosis
HP:0001404	Hepatocellular necrosis
HP:0001405	Periportal fibrosis
HP:0001513	Obesity
HP:0001518	Small for gestational age
HP:0001522	Death in infancy
HP:0001545	Anteriorly placed anus
HP:0001629	Ventricular septal defect
HP:0001631	Atrial septal defect
HP:0001639	Hypertrophic cardiomyopathy
HP:0001640	Cardiomegaly
HP:0001644	Dilated cardiomyopathy
HP:0001645	Sudden cardiac death
HP:0001649	Tachycardia
HP:0001655	Patent foramen ovale
HP:0001657	Prolonged QT interval
HP:0001663	Ventricular fibrillation
HP:0001678	Atrioventricular block
HP:0001698	Pericardial effusion
HP:0001942	Metabolic acidosis
HP:0001958	Nonketotic hypoglycemia
HP:0001985	Hypoketotic hypoglycemia
HP:0001987	Hyperammonemia

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST009391_561	Metabolite levels	7.000000e-06
GCST012442_3	Age-related hearing impairment	9.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009769	histidine measurement

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
D024741	Cardiomyopathy, Hypertrophic, Familial	C14.280.238.100.500; C14.280.484.048.750.070.160.500; C16.320.160
D017074	Common Variable Immunodeficiency	C20.673.330
D016864	Li-Fraumeni Syndrome	C04.700.600; C16.320.700.600; C18.452.284.520
C564011	Pancreatic Hypoplasia, Congenital, with Diabetes Mellitus and Congenital Heart Disease (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105892 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,504 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL230011	TG100-115	2	1,504

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

ChEMBL bioactivities

6 potent at pChembl≥5 of 6 total, top 6 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.29	Kd	50.99	nM	CHEMBL5653589
7.29	ED50	50.99	nM	CHEMBL5653589
6.68	Kd	210.8	nM	CHEMBL3752910
6.68	ED50	210.8	nM	CHEMBL3752910
5.77	Kd	1689	nM	TG100-115
5.28	Kd	5313	nM	CHEMBL4084193

PubChem BioAssay actives

3 with measured affinity, of 243 total; 3 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147780: Binding affinity to human ACADVL incubated for 45 mins by Kinobead based pull down assay	kd	0.0510	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147780: Binding affinity to human ACADVL incubated for 45 mins by Kinobead based pull down assay	kd	0.2108	uM
3-[2,4-diamino-7-(3-hydroxyphenyl)pteridin-6-yl]phenol	1424894: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.6890	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, affects cotreatment, increases methylation, decreases expression, increases expression	4
Tetrachlorodibenzodioxin	increases expression	4
Valproic Acid	increases expression, affects expression, decreases expression	4
sodium arsenate	decreases expression, increases abundance	2
sodium arsenite	increases abundance, increases expression, affects cotreatment, decreases expression	2
perfluorooctanoic acid	increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	2
Acetaminophen	decreases expression, increases expression	2
Arsenic	increases expression, decreases expression, increases abundance, affects cotreatment	2
Bezafibrate	increases activity, increases expression, affects response to substance, decreases oxidation, decreases reaction	2
Diethylhexyl Phthalate	affects response to substance, increases expression	2
Smoke	increases expression, decreases expression, increases abundance	2
Tretinoin	increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
quinone	decreases expression	1
lasiocarpine	decreases expression	1
triphenyl phosphate	affects expression	1
fenofibric acid	affects binding, increases expression	1
pirinixic acid	increases expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
pyrogallol 1,3-dimethyl ether	increases expression, affects cotreatment, affects localization	1
dioctyl adipate	affects response to substance, increases expression	1
beta-lapachone	decreases expression, increases expression	1
tanshinone	increases expression	1
ciglitazone	affects binding, increases expression	1
perfluorooctane sulfonic acid	increases expression	1
azoxystrobin	decreases expression	1
2-palmitoylglycerol	increases expression	1
GW 4064	affects cotreatment, decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3991607	Binding	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by ma	The target landscape of clinical kinase drugs. — Science

Cellosaurus cell lines

9 cell lines: 4 finite cell line, 4 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_4F81	GM17475	Finite cell line	Female
CVCL_7450	GM06127	Finite cell line	Male
CVCL_A2VJ	GM26193	Finite cell line	Male
CVCL_A2VK	GM26194	Finite cell line	Female
CVCL_B2R4	Abcam HEK293T ACADVL KO	Transformed cell line	Female
CVCL_E1PC	HAP1 ACADVL (-) 1	Cancer cell line	Male
CVCL_E1PD	HAP1 ACADVL (-) 2	Cancer cell line	Male
CVCL_E1PE	HAP1 ACADVL (-) 3	Cancer cell line	Male
CVCL_E1PF	HAP1 ACADVL (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00374465	PHASE4	UNKNOWN	Therapy With Verapamil or Carvedilol in Chronic Heart Failure
NCT01293903	PHASE4	COMPLETED	Study of Qiliqiangxin Capsule to Treat Dilated Cardiomyopathy
NCT01557140	PHASE4	COMPLETED	A Randomized Trial of Carvedilol in Chronic Chagas Cardiomyopathy
NCT01917149	PHASE4	COMPLETED	Supramaximal Titrated Inhibition of RAAS in Dilated Cardiomyopathy
NCT02115581	PHASE4	COMPLETED	Coenzyme Q10 Supplementation in Children With Idiopathic Dilated Cardiomyopathy
NCT06236022	PHASE4	RECRUITING	The Effects of Sirolimus in Patients With Dilated Cardiomyopathy Infected With Kaposi Sarcoma-associated Virus
NCT00120055	PHASE4	COMPLETED	Association Between Systemic Exposure of Atorvastatin and Metabolites and Atorvastatin-induced Myotoxicity
NCT03633565	PHASE4	UNKNOWN	Comparative Study of Strategies for Management of Duchenne Myopathy (DM)
NCT00520494	PHASE4	COMPLETED	Efficacy and Safety of Vivaglobin® in Previously Untreated Patients With Primary Immunodeficiency
NCT01289847	PHASE4	COMPLETED	A Study to Find Out How Safe and Effective Gammaplex® is in Young People With Primary Immunodeficiency
NCT01946906	PHASE4	COMPLETED	The Rifaximin Study in CVID
NCT05193552	PHASE4	RECRUITING	Usage of Spirometry in Managing IgG Therapy in CVID With Airway Disease
NCT00333827	PHASE3	COMPLETED	Cell Therapy In Dilated Cardiomyopathy
NCT00505154	PHASE3	COMPLETED	Effect of Rosuvastatin on Left Ventricular Remodeling
NCT01223703	PHASE3	COMPLETED	PUFAs and Left Ventricular Function in Heart Failure
NCT01583114	PHASE3	TERMINATED	PREclinical Mutation CARriers From Families With DIlated Cardiomyopathy and ACE Inhibitors
NCT01914081	PHASE3	UNKNOWN	Resveratrol: A Potential Anti- Remodeling Agent in Heart Failure, From Bench to Bedside
NCT02989181	PHASE3	UNKNOWN	Continues Positive Airway Pressure Treatment for Patients With Dilated Cardiomyopathy and Obstructive Sleep Apnea
NCT03439514	PHASE3	TERMINATED	A Study of ARRY-371797 (PF-07265803) in Patients With Symptomatic Dilated Cardiomyopathy Due to a Lamin A/C Gene Mutation
NCT05237323	PHASE3	COMPLETED	Micophenolate Mofetil Versus Azathioprine in Myocarditis
NCT05849766	PHASE3	COMPLETED	Effect of Dapagliflozin on Cardiac Structure, Function and Secondary Mitral Regurgitation in Patients with Left Ventricle Dysfunction
NCT06250257	PHASE3	RECRUITING	Bromocriptine in Dilated Cardiomyopathy Among Women of Reproductive Age
NCT01225614	PHASE3	UNKNOWN	Efficacy and Tolerance of Early Launching of Nocturnal Non Invasive
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT01464086	PHASE3	COMPLETED	LIFSCREEN : Evaluation of Whole Body MRI for Early Detection of Cancers in Subjects With P53 Mutation (Li-Fraumeni Syndrome)
NCT00168012	PHASE3	COMPLETED	Efficacy and Safety of Intravenous Immunoglobulin IVIG-F10 in Patients With Primary Immunodeficiencies (PID)
NCT00168025	PHASE3	COMPLETED	Efficacy and Safety of Intravenous Immunoglobulin IgPro10 in Patients With Primary Immunodeficiencies (PID)
NCT00220766	PHASE3	COMPLETED	Rapid Infusion of Immune Globulin Intravenous (Human) In Primary Immunodeficiency Patients
NCT00322556	PHASE3	COMPLETED	Safety and Efficacy of Intravenous Immunoglobulin IgPro10 in Patients With Primary Immunodeficiencies (PID)
NCT00542997	PHASE3	COMPLETED	Study of Subcutaneous Immune Globulin in Patients Requiring IgG Replacement Therapy
NCT01884311	PHASE3	COMPLETED	Pharmacokinetics (PK) and Safety of Subgam-VF in Primary Immunodeficiency Diseases
NCT01963143	PHASE3	COMPLETED	Bioequivalence Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Gammaplex® 10 and Gammaplex® 5% in Primary Immunodeficiency Diseases
NCT02247141	PHASE3	COMPLETED	A Multi-centre Open Study to Assess the Safety and Efficacy of Subgam®
NCT00983788	PHASE2	COMPLETED	Effect of Bezafibrate on Muscle Metabolism in Patients With Fatty Acid Oxidation Defects
NCT01886378	PHASE2	COMPLETED	A Study of UX007 (Triheptanoin) in Participants With Long-Chain Fatty Acid Oxidation Disorders (LC-FAOD)
NCT02214160	PHASE2	COMPLETED	Long-Chain Fatty Acid Oxidation Disorders (LC-FAOD) Extension Study for Subjects Previously Enrolled in Triheptanoin Studies
NCT00629018	PHASE2	COMPLETED	Safety and Efficacy Study of Stem Cell Transplantation to Treat Dilated Cardiomyopathy
NCT00629096	PHASE2	COMPLETED	Intracoronary Infusion of Autologous Bone Marrow Cells for Treatment of Idiopathic Dilated Cardiomyopathy
NCT00765518	PHASE2	COMPLETED	Use of Ixmyelocel-T (Formerly Cardiac Repair Cell [CRC] Treatment) in Patients With Heart Failure Due to Dilated Cardiomyopathy (IMPACT-DCM)
NCT00847964	PHASE2	COMPLETED	Safety and Feasibility of Algisyl-LVR™ as a Method of Left Ventricular Restoration in Patients With DCM Undergoing Open-heart Surgery