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). Catalyzes the first of the four reactions of the mitochondrial fatty acid beta-oxidation (FAO) pathway, which consists in the proR-proR stereospecific alpha, beta-dehydrogenation of fatty acyl-CoA thioesters using the electron transfer flavoprotein (ETF) as their physiologic ele….

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): 2,173 total — 148 pathogenic, 329 likely-pathogenic (top 1% of genes corpus-wide)
• GTEx eGene: eQTL in 27 tissues, sQTL in 48 (q < 0.05)
• Phenotypes (HPO): 66
• ChEMBL bioactivity: 1 clinical-phase molecule tested; no curated mechanism-of-action drug
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.08 (unconstrained)
• MANE Select transcript: NM_000018
• Interaction hub: 2,404 STRING partners (top 5% of genes corpus-wide)

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: 137 — 57 nonsense_mediated_decay, 53 protein_coding, 24 retained_intron, 3 protein_coding_CDS_not_defined

MANE Select: ENST00000356839

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 16, TSL 3: 9, TSL 4: 4, TSL 5: 7

ENST00000356839, ENST00000322910, ENST00000350303, 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, ENST00000988269, ENST00000988272, ENST00000988275, ENST00000988277, ENST00000988279, ENST00000988281, ENST00000988286, ENST00000988291, ENST00001020489, ENST00001020491, ENST00001020497, ENST00001020498, ENST00001020499, ENST00001020500, ENST00001020501, ENST00001020502, ENST00001020503, ENST00001020506, ENST00001020509, ENST00001020510, ENST00001020512, ENST00001020513, ENST00001020516, ENST00001020518, ENST00001020520, ENST00001020521, ENST00001020524, ENST00001020525, ENST00001020527, ENST00001020529, ENST00001020530, ENST00001020534, ENST00001020539, ENST00001020540, ENST00001020542, ENST00001020544, ENST00001020547, ENST00001020549, ENST00001020550, ENST00001020552, ENST00001020561, ENST00001020562, ENST00001020564, ENST00001020565, ENST00001020567, ENST00001020569, ENST00001020570, ENST00001020571, ENST00001063156, ENST00001063157, ENST00001110263, ENST00001110265, ENST00001110266, ENST00001127422

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.

Highest expression (Bgee): adrenal gland cortex, apex of heart, adrenal gland, adenohypophysis, lobe of liver.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ACADVL is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 27 tissues and its splicing (sQTL) in 48 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 75 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Thyroid	sqtl	4.0e-160	+3.70	17:7220519:C:T
Cells Cultured fibroblasts	sqtl	6.3e-137	+3.60	17:7220519:C:T
Artery Tibial	sqtl	1.5e-134	+3.35	17:7220519:C:T
Whole Blood	sqtl	2.0e-127	+3.17	17:7220519:C:T
Lung	sqtl	3.2e-121	+3.65	17:7220519:C:T
Esophagus Muscularis	sqtl	2.2e-120	+3.67	17:7220519:C:T
Adipose Subcutaneous	sqtl	3.5e-118	+3.35	17:7220519:C:T
Nerve Tibial	sqtl	1.2e-116	+3.21	17:7220519:C:T
Skin Sun Exposed Lower leg	sqtl	2.7e-114	+3.26	17:7220519:C:T
Adipose Visceral Omentum	sqtl	2.5e-108	+3.66	17:7220519:C:T
Breast Mammary Tissue	sqtl	2.6e-104	+3.64	17:7220519:C:T
Stomach	sqtl	3.7e-91	+3.36	17:7220519:C:T
Colon Sigmoid	sqtl	3.9e-82	+3.59	17:7220519:C:T
Cells EBV-transformed lymphocytes	sqtl	7.6e-77	+3.23	17:7220519:C:T
Heart Atrial Appendage	sqtl	5.3e-75	+3.90	17:7220519:C:T
Artery Aorta	sqtl	1.9e-72	+3.79	17:7220519:C:T
Heart Left Ventricle	sqtl	2.1e-66	+3.94	17:7220519:C:T
Esophagus Gastroesophageal Junction	sqtl	1.0e-64	+3.78	17:7220519:C:T
Pancreas	sqtl	2.0e-51	+3.77	17:7220519:C:T
Testis	sqtl	1.5e-43	+3.64	17:7220519:C:T

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

showing 100 of 295 tissues 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
right ovary	UBERON:0002118	99.59	gold quality
left ovary	UBERON:0002119	99.59	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.59	gold quality
gastrocnemius	UBERON:0001388	99.58	gold quality
body of uterus	UBERON:0009853	99.58	gold quality
lower esophagus	UBERON:0013473	99.58	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.58	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.58	gold quality
small intestine	UBERON:0002108	99.57	gold quality
omental fat pad	UBERON:0010414	99.57	gold quality
gall bladder	UBERON:0002110	99.56	gold quality
upper lobe of left lung	UBERON:0008952	99.56	gold quality
mucosa of stomach	UBERON:0001199	99.55	gold quality
minor salivary gland	UBERON:0001830	99.55	gold quality
peritoneum	UBERON:0002358	99.55	gold quality
right lung	UBERON:0002167	99.53	gold quality
ectocervix	UBERON:0012249	99.52	gold quality
right frontal lobe	UBERON:0002810	99.51	gold quality
esophagus	UBERON:0001043	99.50	gold quality
left uterine tube	UBERON:0001303	99.50	gold quality
skin of abdomen	UBERON:0001416	99.50	gold quality
thyroid gland	UBERON:0002046	99.48	gold quality
adipose tissue of abdominal region	UBERON:0007808	99.48	gold quality
tibial nerve	UBERON:0001323	99.47	gold quality
esophagus mucosa	UBERON:0002469	99.46	gold quality
granulocyte	CL:0000094	99.45	gold quality
stomach	UBERON:0000945	99.45	gold quality
stromal cell of endometrium	CL:0002255	99.44	gold quality
skin of leg	UBERON:0001511	99.44	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.44	gold quality
rectum	UBERON:0001052	99.43	gold quality
muscle of leg	UBERON:0001383	99.43	gold quality
heart	UBERON:0000948	99.42	gold quality
left coronary artery	UBERON:0001626	99.38	gold quality
colonic epithelium	UBERON:0000397	99.32	gold quality
cardiac atrium	UBERON:0002081	99.32	gold quality
upper lobe of lung	UBERON:0008948	99.31	gold quality
coronary artery	UBERON:0001621	99.30	gold quality
saliva-secreting gland	UBERON:0001044	99.28	gold quality
right coronary artery	UBERON:0001625	99.28	gold quality
mouth mucosa	UBERON:0003729	99.28	gold quality
adrenal tissue	UBERON:0018303	99.25	gold quality
fundus of stomach	UBERON:0001160	99.23	gold quality
ascending aorta	UBERON:0001496	99.22	gold quality
thoracic aorta	UBERON:0001515	99.22	gold quality
descending thoracic aorta	UBERON:0002345	99.21	gold quality
duodenum	UBERON:0002114	99.19	gold quality
sigmoid colon	UBERON:0001159	99.17	gold quality
intestine	UBERON:0000160	99.15	gold quality
colon	UBERON:0001155	99.15	gold quality
muscle organ	UBERON:0001630	99.15	gold quality
aorta	UBERON:0000947	99.14	gold quality
popliteal artery	UBERON:0002250	99.12	gold quality
tibial artery	UBERON:0007610	99.12	gold quality
jejunal mucosa	UBERON:0000399	99.08	gold quality
large intestine	UBERON:0000059	99.05	gold quality
spleen	UBERON:0002106	99.03	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.01	gold quality
adult mammalian kidney	UBERON:0000082	98.97	gold quality
pancreas	UBERON:0001264	98.93	gold quality
liver	UBERON:0002107	98.91	gold quality
jejunum	UBERON:0002115	98.91	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.90	gold quality
heart right ventricle	UBERON:0002080	98.89	gold quality
ileal mucosa	UBERON:0000331	98.87	gold quality
subcutaneous adipose tissue	UBERON:0002190	98.87	gold quality
cerebellum	UBERON:0002037	98.81	gold quality
cingulate cortex	UBERON:0003027	98.77	gold quality
adipose tissue	UBERON:0001013	98.76	gold quality
skeletal muscle tissue	UBERON:0001134	98.76	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Skeletal muscle	tissue	796.3	medium
Tongue	tissue	763.4
Liver	tissue	357.4	medium
Adrenal gland	tissue	349.1	high
Heart muscle	tissue	319.1	high
Duodenum	tissue	288.6	high
Small intestine	tissue	255.0	high
Pituitary gland	tissue	208.3
Adipose tissue	tissue	185.6	low
Pancreas	tissue	181.1	medium
Choroid plexus	tissue	171.6
Stomach 1	tissue	163.8	high
Kidney	tissue	160.9	medium
Esophagus	tissue	159.4	medium
Parathyroid gland	tissue	150.1	high
Salivary gland	tissue	149.5	medium
Colon	tissue	146.6	high
Vagina	tissue	125.7	low
Rectum	tissue	123.7	medium
Seminal vesicle	tissue	107.5	medium
Placenta	tissue	105.4	medium
Urinary bladder	tissue	104.3	medium
Smooth muscle	tissue	103.3	low
Skin 1	tissue	98.5	medium
Prostate	tissue	98.0	medium
Bone marrow	tissue	97.7	medium
Thyroid gland	tissue	95.4	medium
Breast	tissue	94.5	medium
Cervix	tissue	89.1	medium
Gallbladder	tissue	87.0	high
Lung	tissue	81.2	high
Thymus	tissue	77.8
Tonsil	tissue	77.8	medium
Appendix	tissue	74.3	medium
Fallopian tube	tissue	69.9	medium
Ovary	tissue	69.2	low
Locus coeruleus	tissue	66.0
Spleen	tissue	62.6	low
Endometrium 1	tissue	59.4	medium
Hippocampus	tissue	58.1	medium
Lymph node	tissue	48.7	low
Nucleus accumbens	tissue	48.0
Spinal cord	tissue	42.6
Testis	tissue	42.4	medium
Epididymis	tissue	42.0	low
Postcentral gyrus	tissue	40.8
Frontal cortex	tissue	37.6
Caudate putamen	tissue	36.2
Medulla oblongata	tissue	35.7
Substantia nigra	tissue	35.6
Thalamus	tissue	33.9
Superior colliculi	tissue	33.9
Pons	tissue	33.4
Retina	tissue	32.4
Midbrain	tissue	31.8
Corpus callosum	tissue	30.7
Hypothalamus	tissue	28.1
Putamen	tissue	27.2
Ventral forebrain	tissue	25.9
Periaqueductal gray	tissue	25.8

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Blood vessel (111.6), Anterior thalamic nucleus, ventral (93.3), Globus pallidus, externus (86.8), Posterior thalamic nucleus (86.5), Cerebellar nuclei (82.0).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TFAP2A

miRNA regulators (miRDB)

Targeting ACADVL by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

21 miRNAs:

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

gnomAD constraint: pLI 2.43e-22, LOEUF 1.08, missense Z 0.101 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000356839 — one region, missense o/e 1.02. 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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:895149) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 39 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal myocardial fiber morphology	3
increased susceptibility to induced morbidity/mortality	3
abnormal heart morphology	2
impaired glucose tolerance	2
abnormal amino acid level	2
decreased heart rate	2
impaired adaptive thermogenesis	2
abnormal adipose tissue morphology	1
hypoglycemia	1
increased body weight	1
abnormal cardiovascular system physiology	1
increased tumor incidence	1
premature death	1
abnormal lipid homeostasis	1
hepatic steatosis	1
dilated heart left ventricle	1
dilated cardiomyopathy	1
increased heart weight	1
fatigue	1
abnormal brown adipose tissue morphology	1
abnormal skeletal muscle fiber morphology	1
abnormal heart left ventricle morphology	1
increased circulating carnitine level	1
myocardial fiber degeneration	1
lethargy	1

+14 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Escherichia coli K-12	P0A9U8	100.0%	Diamond
Escherichia coli CFT073	P0A9U9	100.0%	Diamond
Escherichia coli O157:H7	P0A9V0	100.0%	Diamond
Mycobacterium tuberculosis variant bovis AF2122/97	P63428	100.0%	Diamond
Mycobacterium tuberculosis CDC1551	P9WQF6	100.0%	Diamond
Mycobacterium tuberculosis H37Rv	P9WQF7	100.0%	Diamond
Pan troglodytes	A5A6I0	99.5%	Diamond
Pongo abelii	Q5RAS0	99.3%	Diamond
Macaca fascicularis	Q8HXX8	96.8%	Diamond
Caenorhabditis briggsae	A8XNF0	95.4%	Diamond
Sus scrofa	P41367	92.1%	Diamond
Bos taurus	Q3SZB4	92.1%	Diamond
Mycobacterium leprae TN	P46703	92.0%	Diamond
Oryza sativa Japonica Group	Q75IM9	86.7%	Diamond
Arabidopsis thaliana	Q9SWG0	86.7%	Diamond
Solanum tuberosum	Q9FS87	84.4%	Diamond
Cupriavidus necator N-1	F8GVD3	81.4%	Diamond
Syntrophus aciditrophicus SB	Q2LQN9	73.4%	Diamond
Geobacter metallireducens GS-15	Q39QF5	73.4%	Diamond
Dictyostelium discoideum	Q54R47	68.8%	Diamond
Acetobacterium woodii DSM 1030	H6LGM6	66.4%	Diamond
Clostridium sporogenes ATCC 15579	J7TF92	66.4%	Diamond
Paraburkholderia xenovorans LB400	Q13PC1	64.9%	Diamond
Bacillus subtilis subsp. subtilis str. 168	P45867	60.2%	Diamond
Clostridium acetobutylicum ATCC 824	P52042	60.2%	Diamond
Megasphaera elsdenii	Q06319	56.9%	Diamond
Drechslerella dactyloides	A0AAD6NFV5	54.6%	Diamond
Anaerotignum propionicum	G3KIM8	53.8%	Diamond
Streptomyces coelicolor A3(2)	O54143	47.4%	Diamond
Pseudomonas protegens Pf-5	Q4KCY6	47.4%	Diamond
Aromatoleum aromaticum EbN1	Q5P5Z9	40.7%	Diamond
Desulfococcus multivorans	C3UVB0	40.4%	Diamond
Cereibacter sphaeroides	D3JV03	39.9%	Diamond
Alternaria alternata	Q50LG2	36.8%	Diamond
Thauera aromatica	Q9KJE8	35.5%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
CLDN7	protein-coding	1366
DVL2	protein-coding	1856
CTDNEP1	protein-coding	23399
ELP5	protein-coding	23587
MIR324	ncRNA	442898
PHF23	protein-coding	79142
DLG4	protein-coding	1742
ASGR1	protein-coding	432
GABARAP	protein-coding	11337

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. Catalyzes the first of the four reactions of the mitochondrial fatty acid beta-oxidation (FAO) pathway, which 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). The mitochondrial FAO pathway is the major energy-producing process in tissues and is performed through cycles of four consecutive reactions. Each FAO cycle shortens the fatty acyl-CoA by two carbons, yielding one acetyl-CoA (for the citric acid cycle), one FADH(2), and one NADH (which donate electrons to the respiratory chain for ATP production). 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, but can also catalyze monounsaturated fatty acids such as oleate ((9Z)-octadecenoate), (9Z)-hexadecenoate, and others. Can use (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate as substrate in vitro (which is not primarily used for energy but mainly beta-oxidized in the peroxisomes). In addition, based on its established catalytic mechanism, and combined genetic interaction or mutant phenotype evidence, it is predicted to act also on substrates that have not been tested experimentally but are metabolized by mitochondrial FAO, including long-chain unsaturated fatty acids such as linoleate (9Z,12Z-octadecadienoate), linolenate (9Z,12Z,15Z-octadecatrienoate), and others. Among the different mitochondrial acyl-CoA dehydrogenases, its FAO activity overlaps with that of ACAD9 and ACADL, but plays a primary role in tissues where it is the main long-chain ACAD expressed, such as the heart and skeletal muscle.

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)

• 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)
• (7Z)-hexadecenoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E,7Z)-hexadecadienoyl-CoA + reduced [electron-transfer flavoprotein] (RHEA:47432)

UniProt features (136 total): sequence variant 47, helix 28, modified residue 23, strand 10, turn 6, 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 by resolution:

PDB	Title	Method	Resolution (Å)
7S7G	Crystal Structure Analysis of Human VLCAD	X-RAY DIFFRACTION	1.34
2UXW	Crystal structure of human very long chain acyl-CoA dehydrogenase (ACADVL)	X-RAY DIFFRACTION	1.45
3B96	Structural Basis for Substrate Fatty-Acyl Chain Specificity: Crystal Structure of Human …	X-RAY DIFFRACTION	1.91

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Oxidoreductases, Metabolic proteins, Predicted intracellular proteins, Disease related genes, Potential drug targets, Human disease related genes, Congenital disorders of metabolism, Congenital disorders of lipid/glycolipid metabolism

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): mitochondria; nucleoli; nucleoplasm

Antibody reliability (HPA): IH enhanced · IF supported

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)

Position	Role
462	proton acceptor

Ligand- & substrate-binding residues (5)

Position	Role
562	FAD
214–223	FAD
249–251	FAD
461–463	substrate
464–466	FAD

Post-translational modifications (23)

Type	Positions
N6-acetyllysine	51, 71, 239, 276, 278, 298, 331, 482, 550, 556
N6-succinyllysine	71, 195, 239, 276, 278, 331, 372, 482, 556, 639
S-nitrosocysteine	237
Phosphoserine	517, 522

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

2 curated (TAS) of 11; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

11 pathways:

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

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 (11): temperature homeostasis (GO:0001659), 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), 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 (5): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial matrix (GO:0005759), mitochondrial membrane (GO:0031966), mitochondrial nucleoid (GO:0042645)

Reactome top-level categories

9 top-level categories:

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

41 GO namespaces:

Category	Terms
acyl-CoA dehydrogenase activity	3
mitochondrion	3
negative regulation of fatty acid metabolic process	2
fatty acid oxidation	2
multicellular organismal-level homeostasis	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
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
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
intracellular organelle lumen	1
mitochondrial envelope	1
organelle membrane	1
mitochondrial matrix	1
nucleoid	1
intracellular membraneless organelle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 10 of 25 annotations. The rest are phylogenetic / computational / electronic (IEA).

10 experimentally-supported GO terms:

GO term	NS	Evidence
epithelial cell differentiation	BP	expression pattern
fatty acid beta-oxidation using acyl-CoA dehydrogenase	BP	direct assay
mitochondrial membrane	CC	direct assay
mitochondrial nucleoid	CC	direct assay
mitochondrion	CC	direct assay
acyl-CoA dehydrogenase activity	MF	mutant phenotype
flavin adenine dinucleotide binding	MF	direct assay
identical protein binding	MF	direct assay
long-chain fatty acyl-CoA dehydrogenase activity	MF	direct assay
very-long-chain fatty acyl-CoA dehydrogenase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 2,404 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACADVL	HADHA	P40939	909
ACADVL	CPT2	P23786	905
ACADVL	ACSL1	P33121	770
ACADVL	HADHB	P55084	758
ACADVL	HADH	Q16836	741
ACADVL	ACAA2	P42765	716
ACADVL	SLC25A20	O43772	702
ACADVL	CPT1A	P50416	698
ACADVL	ETFDH	Q16134	688
ACADVL	ACOX1	Q15067	673
ACADVL	ECHS1	P30084	663
ACADVL	PLIN2	Q99541	657
ACADVL	ECH1	Q13011	651
ACADVL	CPT1B	Q92523	623
ACADVL	PPARA	Q07869	613

IntAct

Human interaction partners of ACADVL in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

10 partners by confidence:

Partner	Interaction type	MIscore	Records
TAF1B	physical association	0.560	3
APC	association	0.530	1
TRAT1	association	0.530	1
SURF1	physical association	0.400	1
GPHN	physical association	0.370	1
RPSA	physical association	0.370	1
EEF2K	association	0.350	1
EGFR	association	0.350	1
HIBCH	association	0.350	1
NPR2	association	0.350	1

BioGRID (206 interactions; top human partners by supporting records): SURF1 (Affinity Capture-MS; 4 records), ECSIT (Affinity Capture-MS; 3 records), HIBCH (Affinity Capture-MS; 3 records), HMGCL (Affinity Capture-MS; 3 records), APC (Affinity Capture-MS; 2 records), CLASRP (Affinity Capture-MS; 2 records), CLPP (Proximity Label-MS; 2 records), CS (Proximity Label-MS; 2 records), DHRS4 (Affinity Capture-MS; 2 records), FAM60A (Affinity Capture-MS; 2 records), MRM1 (Affinity Capture-MS; 2 records), NDUFA13 (Affinity Capture-MS; 2 records), NPPA (Affinity Capture-MS; 2 records), PARK2 (Affinity Capture-MS; 2 records), PDE4DIP (Affinity Capture-MS; 2 records)

SIGNOR signaling

5 signaling 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

Genetic variants

Variant evidence for ACADVL: 2,173 ClinVar records (477 pathogenic / likely pathogenic); 287 ClinGen expert-panel interpretations; 2 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

2,173 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	148
Likely pathogenic	329
Uncertain significance	646
Likely benign	808
Benign	35

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 477 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
21025	NM_000018.4(ACADVL):c.848T>C (p.Val283Ala)	Pathogenic	reviewed by expert panel	39
203585	NM_000018.4(ACADVL):c.1376G>A (p.Arg459Gln)	Pathogenic	reviewed by expert panel	19
21016	NM_000018.4(ACADVL):c.1322G>A (p.Gly441Asp)	Pathogenic	reviewed by expert panel	17
1624	NM_000018.4(ACADVL):c.343del	Pathogenic	reviewed by expert panel	16
166638	NM_000018.4(ACADVL):c.65C>A (p.Ser22Ter)	Pathogenic	reviewed by expert panel	14
189116	NM_000018.4(ACADVL):c.298_299del (p.Gln100fs)	Pathogenic	reviewed by expert panel	14
1626	NM_000018.4(ACADVL):c.385GAG[1] (p.Glu130del)	Pathogenic	reviewed by expert panel	13
188884	NM_000018.4(ACADVL):c.685C>T (p.Arg229Ter)	Pathogenic	reviewed by expert panel	10
194317	NM_000018.4(ACADVL):c.1357C>T (p.Arg453Ter)	Pathogenic	reviewed by expert panel	9
370279	NM_000018.4(ACADVL):c.1077+2T>C	Pathogenic	reviewed by expert panel	9
370686	NM_000018.4(ACADVL):c.1077_1077+1delinsCAC	Pathogenic	reviewed by expert panel	9
203594	NM_000018.4(ACADVL):c.343-1G>A	Pathogenic	reviewed by expert panel	8
370717	NM_000018.4(ACADVL):c.644_647del (p.Phe214_Cys215insTer)	Pathogenic	reviewed by expert panel	8
422995	NM_000018.4(ACADVL):c.428_467del (p.Gly143fs)	Pathogenic	reviewed by expert panel	8
818026	NM_000018.4(ACADVL):c.1145del (p.Lys382fs)	Pathogenic	reviewed by expert panel	8

Per-variant reference — Sugi Variant

Explore ACADVL’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

ClinGen expert-panel interpretations (287)

Expert ACMG interpretations from ACADVL VCEP for very long chain acyl-CoA dehydrogenase deficiency — a higher-authority tier than individual ClinVar submissions.

Assertion	Variants
Pathogenic	42
Likely Pathogenic	133
Uncertain Significance	73
Likely Benign	26
Benign	13

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 35 predictions of 1,646):

Position(s)	Effect	Δscore	Sites
17:7220761	acceptor_gain	1.0000
17:7220764–7220765	acceptor_loss	1.0000	5
17:7220831–7220832	donor_loss	1.0000	5
17:7222303–7222304	donor_loss	1.0000	5
17:7222653–7222654	acceptor_gain	1.0000	2
17:7223622	acceptor_gain	1.0000
17:7223966–7223967	acceptor_loss	1.0000	5
17:7224070–7224071	donor_loss	1.0000	5
17:7224236	donor_gain	1.0000
17:7224319–7224320	acceptor_loss	1.0000	5

AlphaMissense

1,468 missense substitutions predicted likely pathogenic (of 4,263 scored), across 393 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
F461	8	0.982	0.998
D454	8	0.980	0.994
D224	8	0.975	0.994
F262	8	0.967	0.995
F330	8	0.966	0.995
D405	8	0.957	0.991
D171	8	0.956	0.978
H181	8	0.941	0.988
F282	8	0.933	0.997
D431	8	0.929	0.984
F369	8	0.922	0.995
F458	8	0.911	0.979
D466	8	0.890	0.970
M404	8	0.860	0.962
F88	8	0.827	0.951
F214	7	0.995	0.999
R341	7	0.994	0.999
E462	7	0.988	0.998
W249	7	0.986	0.998
E218	7	0.984	0.995

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	7.42e-08
Liver Hepatocellular Carcinoma (validation)	favorable	0.000689

Disease associations

OMIM: gene MIM:609575 | disease phenotypes: MIM:201475, MIM:600001, MIM:618793, MIM:151623, MIM:609266, MIM:261800

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
very long chain acyl-CoA dehydrogenase deficiency	Definitive	Autosomal recessive	6

ClinGen Gene-Disease Validity

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

1 validity classifications:

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

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (15 panels, 11 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

15 panels:

Panel	Rating
Acute rhabdomyolysis	green
DDG2P	green
Fetal anomalies	green
Hyperammonaemia	green
Likely inborn error of metabolism	green
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies	green
Other rare neuromuscular disorders	green
Paediatric or syndromic cardiomyopathy	green
Rhabdomyolysis and metabolic muscle disorders	green
Undiagnosed metabolic disorders	green
Unexplained death in infancy and sudden unexplained death in childhood	green
Hypotonic infant	amber
Intellectual disability	amber
Leukodystrophy, childhood onset	amber
Paediatric disorders	amber

Mondo (7): very long chain acyl-CoA dehydrogenase deficiency (MONDO:0008723), pancreatic hypoplasia-diabetes-congenital heart disease syndrome (MONDO:0010802), intellectual developmental disorder 62 (MONDO:0032919), myopathy (MONDO:0005336), Li-Fraumeni syndrome (MONDO:0018875), cardiac rhythm disease (MONDO:0007263), isolated Pierre-Robin syndrome (MONDO:0009869)

Orphanet (4): Very long chain acyl-CoA dehydrogenase deficiency (Orphanet:26793), Pancreatic hypoplasia-diabetes-congenital heart disease syndrome (Orphanet:2255), Li-Fraumeni syndrome (Orphanet:524), Isolated Pierre Robin sequence (Orphanet:718)

HPO phenotypes

showing 60 of 66 phenotypes (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
HP:0002013	Vomiting
HP:0002020	Gastroesophageal reflux
HP:0002045	Hypothermia
HP:0002069	Bilateral tonic-clonic seizure
HP:0002090	Pneumonia
HP:0002098	Respiratory distress
HP:0002240	Hepatomegaly
HP:0002280	Enlarged cisterna magna
HP:0002572	Episodic vomiting
HP:0002789	Tachypnea
HP:0002876	Episodic tachypnea
HP:0002901	Hypocalcemia
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0003075	Hypoproteinemia
HP:0003215	Elevated urinary dicarboxylic acid level
HP:0003234	Decreased circulating carnitine concentration
HP:0003236	Elevated circulating creatine kinase activity
HP:0003394	Muscle spasm
HP:0003552	Muscle stiffness
HP:0003593	Infantile onset
HP:0003623	Neonatal onset
HP:0003738	Exercise-induced myalgia
HP:0004756	Ventricular tachycardia
HP:0005943	Respiratory arrest
HP:0008305	Exercise-induced myoglobinuria
HP:0008947	Floppy infant
HP:0009045	Exercise-induced rhabdomyolysis
HP:0011123	Inflammatory abnormality of the skin
HP:0011675	Arrhythmia
HP:0011968	Feeding difficulties

GWAS associations

2 associations:

Study	Trait	p-value
GCST012442_35	Age-related hearing impairment	9e-9
GCST009391_586	Metabolite levels	7e-6

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0009769	histidine measurement

MeSH disease descriptors

3 disease descriptors:

Descriptor	Name	Tree numbers
D016864	Li-Fraumeni Syndrome	C04.700.600; C16.320.700.600; C18.452.284.520
D010855	Pierre Robin Syndrome	C05.500.460.606; C05.660.207.540.460.606; C07.320.440.606; C07.650.500.460.606; C16.131.621.207.540.460.606; C16.131.850.500.460.606
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

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,586 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

1 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL230011	TG100-115	2	1,586

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (2 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

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 244 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 cotreatment, increases methylation, decreases expression, increases expression, affects expression	4
Tetrachlorodibenzodioxin	increases expression	4
Valproic Acid	affects expression, decreases expression, increases expression	4
sodium arsenate	decreases expression, increases abundance	2
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases 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	decreases expression, increases abundance, affects cotreatment, increases expression	2
Bezafibrate	decreases oxidation, decreases reaction, increases activity, increases expression, affects response to substance	2
Diethylhexyl Phthalate	increases expression, affects response to substance	2
Smoke	decreases expression, increases abundance, increases expression	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	affects cotreatment, affects localization, increases expression	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)

Via MONDO — disease-level, not drug-specific.

showing 60 of 290 trials:

NCT	Phase	Status	Title
NCT00120055	Phase 4	COMPLETED	Association Between Systemic Exposure of Atorvastatin and Metabolites and Atorvastatin-induced Myotoxicity
NCT03633565	Phase 4	UNKNOWN	Comparative Study of Strategies for Management of Duchenne Myopathy (DM)
NCT00520494	Phase 4	COMPLETED	Efficacy and Safety of Vivaglobin® in Previously Untreated Patients With Primary Immunodeficiency
NCT01289847	Phase 4	COMPLETED	A Study to Find Out How Safe and Effective Gammaplex® is in Young People With Primary Immunodeficiency
NCT01946906	Phase 4	COMPLETED	The Rifaximin Study in CVID
NCT05193552	Phase 4	RECRUITING	Usage of Spirometry in Managing IgG Therapy in CVID With Airway Disease
NCT00146822	Phase 4	COMPLETED	REFLEx Study (ENDOTAK RELIANCE G Evaluation of Handling and Electrical Performance
NCT00187239	Phase 4	COMPLETED	Reduce Ventricular Pacing in Dual Chamber Implantable Cardioverter Defibrillators Using AutoIntrinsic Conduction Search Study
NCT00247533	Phase 4	UNKNOWN	Cerebral Artery Stenosis, Coronary Artery Disease and Arrhythmia
NCT00282620	Phase 4	UNKNOWN	Magnesium to Reduce Implantable Cardioverter Defibrillator (ICD) Shocks and Improve Patient’s Quality of Life.
NCT00290056	Phase 4	UNKNOWN	Effect of Supplemental Intake of Omega-3 Polyunsaturated Fatty Acids on the Rate and Complexity of Spontaneously Occurring Ventricular and Supraventricular Arrhythmias in Patients With Implantable Cardioverter Defibrillator (ICD) - A Randomized Clinical Trial
NCT00313443	Phase 4	COMPLETED	Concentrations of Amiodarone in Fat Tissue During Chronic Treatment
NCT00457340	Phase 4	COMPLETED	Atorvastatin For The Reduction Of Ventricular Arrhythmias
NCT00507390	Phase 4	WITHDRAWN	Omega 3 Polyunsaturated Fatty Acid Supplements (PUFAs) and Microvolt T Wave Alternans (TWA) in Patients With Ventricular Arrhythmia
NCT00575523	Phase 4	COMPLETED	Atropine for Prevention of Dysrhythmias Caused by Percutaneous Ethanol Instillation for Hepatoma Therapy
NCT00579098	Phase 4	COMPLETED	The Use of Statins Following a Left Atrial Catheter Ablation Procedure to Prevent Atrial Fibrillation
NCT01613092	Phase 4	COMPLETED	Prevention of Arrhythmia Device Infection Trial (PADIT)
NCT01628666	Phase 4	COMPLETED	Prevention of Arrhythmia Device Infection Trial (PADIT)
NCT01717469	Phase 4	UNKNOWN	Safety and the Effects of Isolated Left Ventricular Pacing in Patients With Bradyarrhythmias
NCT01819064	Phase 4	COMPLETED	Heart Rate Response to Atropine Doses Less Than 0.1mg IV to Anesthetized Infants
NCT01834872	Phase 4	UNKNOWN	Safety and Feasibility of Arrhythmia Ablation Using the Amigo Remote Robotic System as Compared With Manual Ablation
NCT01841242	Phase 4	COMPLETED	Comparison of Alcoholic Chlorhexidine 2% Versus Alcoholic Povidone Iodine for Infections Prevention With Cardiac Resynchronization Therapy Device Implantation
NCT01991223	Phase 4	UNKNOWN	Dexmedetomidine for Catheter-related Bladder Discomfort
NCT02045173	Phase 4	COMPLETED	Automate Detection of Sleep Apnea by ApneascanTM
NCT02203630	Phase 4	TERMINATED	Phenylephrine Versus Norepinephrine for Septic Shock in Critically Ill Patients
NCT03273634	Phase 4	COMPLETED	The Effect of Proton Pump Inhibition on Palpitations
NCT03289429	Phase 4	UNKNOWN	Antiarrhythmic and Cardioprotective Effects of Atorvastatin Versus Magnesium Sulfate in Cardiac Valve Replacement Surgery
NCT03895411	Phase 4	UNKNOWN	Efficacy and Safety of Sotalol in Children With Arrhythmia
NCT05486377	Phase 4	COMPLETED	Remimazolam vs Desflurane for General Anesthesia for Ablation of Arrhythmia
NCT06574555	Phase 4	COMPLETED	Norepinephrine ED90 Bolus After Spinal Anesthesia in Cesarean Section
NCT07617376	Phase 4	RECRUITING	Pre-discharge Influenza Vaccination in Patients Hospitalized for Acute Cardiac Conditions
NCT01225614	Phase 3	UNKNOWN	Efficacy and Tolerance of Early Launching of Nocturnal Non Invasive
NCT03414970	Phase 3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT01464086	Phase 3	COMPLETED	LIFSCREEN : Evaluation of Whole Body MRI for Early Detection of Cancers in Subjects With P53 Mutation (Li-Fraumeni Syndrome)
NCT00168012	Phase 3	COMPLETED	Efficacy and Safety of Intravenous Immunoglobulin IVIG-F10 in Patients With Primary Immunodeficiencies (PID)
NCT00168025	Phase 3	COMPLETED	Efficacy and Safety of Intravenous Immunoglobulin IgPro10 in Patients With Primary Immunodeficiencies (PID)
NCT00220766	Phase 3	COMPLETED	Rapid Infusion of Immune Globulin Intravenous (Human) In Primary Immunodeficiency Patients
NCT00322556	Phase 3	COMPLETED	Safety and Efficacy of Intravenous Immunoglobulin IgPro10 in Patients With Primary Immunodeficiencies (PID)
NCT00542997	Phase 3	COMPLETED	Study of Subcutaneous Immune Globulin in Patients Requiring IgG Replacement Therapy
NCT01884311	Phase 3	COMPLETED	Pharmacokinetics (PK) and Safety of Subgam-VF in Primary Immunodeficiency Diseases
NCT01963143	Phase 3	COMPLETED	Bioequivalence Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Gammaplex® 10 and Gammaplex® 5% in Primary Immunodeficiency Diseases
NCT02247141	Phase 3	COMPLETED	A Multi-centre Open Study to Assess the Safety and Efficacy of Subgam®
NCT00000464	Phase 3	COMPLETED	Cardiac Arrest in Seattle: Conventional Versus Amiodarone Drug Evaluation (CASCADE)
NCT00000476	Phase 3	COMPLETED	Digitalis Investigation Group (DIG)
NCT00000480	Phase 3	COMPLETED	Multicenter Unsustained Tachycardia Trial (MUSTT)
NCT00000492	Phase 3	COMPLETED	Beta-Blocker Heart Attack Trial (BHAT)
NCT00000502	Phase 3	COMPLETED	Evaluation of SC-V Versus Conventional CPR
NCT00000517	Phase 3	COMPLETED	Boston Area Anticoagulation Trial for Atrial Fibrillation (BAATAF)
NCT00000518	Phase 3	COMPLETED	Electrophysiologic Study Versus Electrocardiographic Monitoring (ESVEM)
NCT00000531	Phase 3	COMPLETED	Antiarrhythmics Versus Implantable Defibrillators (AVID)
NCT00000540	Phase 3	COMPLETED	Coronary Artery Bypass Graft (CABG) Patch Trial
NCT00000556	Phase 3	COMPLETED	Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM)
NCT00000561	Phase 3	COMPLETED	Mode Selection Trial in Sinus Node Dysfunction (MOST)
NCT00000609	Phase 3	COMPLETED	Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT)
NCT00004559	Phase 3	COMPLETED	Fatty Acid Antiarrhythmia Trial (FAAT)
NCT00004560	Phase 3	COMPLETED	Public Access Defibrillation (PAD) Community Trial
NCT00035490	Phase 3	COMPLETED	Efficacy and Safety Evaluation of Azimilide Dihydrochloride in Patients With Implantable Cardioverter Defibrillators
NCT00098137	Phase 3	COMPLETED	Trial to Investigate the Efficacy of Olmesartan in Paroxysmal Atrial Fibrillation
NCT00110838	Phase 3	COMPLETED	SOFA: Study on Omega-3 Fatty Acids and Ventricular Arrhythmia
NCT00116428	Phase 3	COMPLETED	NAVISTAR® THERMOCOOL® Catheter for the Radiofrequency Ablation of Symptomatic Paroxysmal Atrial Fibrillation

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for ACADVL across ~30M SureChEMBL compounds — explore on Sugi Predict.