ACADVL

acyl-CoA dehydrogenase very long chain, the group of Acyl-CoA dehydrogenase family

Basic information

Region (hg38): 17:7217125-7225266

Links

ENSG00000072778 ∙ NCBI:37 ∙ OMIM:609575 ∙ HGNC:92 ∙ Uniprot:P49748 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• very long chain acyl-CoA dehydrogenase deficiency (Definitive), mode of inheritance: AR
• very long chain acyl-CoA dehydrogenase deficiency (Strong), mode of inheritance: AR
• very long chain acyl-CoA dehydrogenase deficiency (Strong), mode of inheritance: AR
• very long chain acyl-CoA dehydrogenase deficiency (Supportive), mode of inheritance: AR
• very long chain acyl-CoA dehydrogenase deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Acyl-CoA dehydrogenase, very long chain, deficiency of	AR	Biochemical; Cardiovascular; Musculoskeletal; Renal	There are multiple forms of VLCAD deficiency, and interventions depend on the form (typical medical/dietary therapy considerations include IV glucose/carnitine in initial phases, as well as low-fat, diet with MCT oil and carnitine, or triheptanoin, and avoidance of fasting); In the severe, early-onset form, medical treatment of cardiomyopathy may be beneficial; In thechildhood onset form, treatment of hypoketotic hypoglycemia may be beneficial; In the adult-onset, myopathic form, preventive measures related to with irhabdomyolysis, and myoglobinuria after exercise or fasting may be beneficial	Biochemical; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic; Renal	4022672; 2059253; 2000272; 1527994; 8422439; 8356011; 8145917; 7668252; 7769092; 7479827; 8739959; 8554073; 9709714; 9877038; 9546340; 9973285; 10077518; 10790204; 11158518; 11524729; 15210884; 17636072; 19327992; 19208414; 19399638; 19452263; 21531094; 21814341; 22847164; 23480858; 33610471

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ACADVL gene.

• Very long chain acyl-CoA dehydrogenase deficiency (124 variants)
• not provided (18 variants)
• Inborn genetic diseases (5 variants)
• ACADVL-related disorder (5 variants)
• Myopathy;Rhabdomyolysis (1 variants)
• Abnormal circulating enzyme concentration;Rhabdomyolysis (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ACADVL gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	1	1	11	327	3	343
missense	25	113	417	2	4	561
nonsense	21	25	2			48
start loss		1				1
frameshift	57	108	5			170
inframe indel	4	3	10			17
splice donor/acceptor (+/-2bp)	18	66	3	1		88
splice region		6	37	89	3	135
non coding		2	32	277	25	336
Total	126	319	480	607	32

Highest pathogenic variant AF is 0.00109

Variants in ACADVL

This is a list of pathogenic ClinVar variants found in the ACADVL region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-7217134-CAGAG-C		Intellectual developmental disorder 62	Likely pathogenic (Jan 25, 2023)
17-7217159-T-C			Benign (Dec 01, 2022)
17-7217169-G-A		ACADVL-related disorder	Likely benign (Jul 10, 2024)
17-7217174-G-A		Very long chain acyl-CoA dehydrogenase deficiency	Uncertain significance (Mar 29, 2018)
17-7217739-A-G		Primary familial hypertrophic cardiomyopathy • Very long chain acyl-CoA dehydrogenase deficiency	Uncertain significance (Jan 01, 2023)
17-7217740-T-TAGAAGC		Very long chain acyl-CoA dehydrogenase deficiency	Uncertain significance (Feb 03, 2017)
17-7217754-C-T		Very long chain acyl-CoA dehydrogenase deficiency	Uncertain significance (Feb 28, 2017)
17-7217769-C-T		Very long chain acyl-CoA dehydrogenase deficiency	Uncertain significance (Mar 07, 2018)
17-7217776-G-A		Very long chain acyl-CoA dehydrogenase deficiency	Uncertain significance (Aug 02, 2017)
17-7217786-C-A		Very long chain acyl-CoA dehydrogenase deficiency	Benign (Nov 11, 2023)
17-7217796-G-GCGATGA		Very long chain acyl-CoA dehydrogenase deficiency	Uncertain significance (Oct 14, 2017)
17-7217801-GACAGC-G		Very long chain acyl-CoA dehydrogenase deficiency	Uncertain significance (Mar 07, 2018)
17-7218228-C-T		Intellectual developmental disorder 62	Uncertain significance (Mar 16, 2022)
17-7218244-ACT-A		Inborn genetic diseases	Uncertain significance (May 14, 2022)
17-7218275-A-C			Uncertain significance (Jun 13, 2023)
17-7218281-T-A			Uncertain significance (Feb 27, 2023)
17-7218550-C-T			Uncertain significance (Feb 07, 2022)
17-7218565-T-C		DLG4-related disorder	Benign (Jan 01, 2024)
17-7218592-C-A			Uncertain significance (Sep 10, 2019)
17-7218621-C-T			Likely pathogenic (Feb 01, 2021)
17-7218634-T-C			Uncertain significance (Dec 04, 2023)
17-7218640-C-G		Autism spectrum disorder • Inborn genetic diseases	Uncertain significance (Mar 21, 2022)
17-7218848-A-C		Intellectual developmental disorder 62	Uncertain significance (-)
17-7219637-G-A			Benign (Jun 28, 2018)
17-7219691-C-T			Likely benign (Jul 21, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ACADVL	protein_coding	protein_coding	ENST00000543245	21	8149

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.24e-15	0.285	125673	0	75	125748	0.000298

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.210	390	379	1.03	0.0000227	4385
Missense in Polyphen		136	139.4	0.97558		1639
Synonymous	-1.74	171	144	1.18	0.00000864	1383
Loss of Function	1.32	27	35.5	0.761	0.00000186	422

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00102	0.00102
Ashkenazi Jewish	0.00	0.00
East Asian	0.000272	0.000272
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000308	0.000308
Middle Eastern	0.000272	0.000272
South Asian	0.000196	0.000196
Other	0.000652	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Active toward esters of long-chain and very long chain fatty acids such as palmitoyl-CoA, myristoyl-CoA and stearoyl-CoA. Can accommodate substrate acyl chain lengths as long as 24 carbons, but shows little activity for substrates of less than 12 carbons. {ECO:0000269|PubMed:18227065}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:10077518, ECO:0000269|PubMed:8554073, ECO:0000269|PubMed:9546340}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Fatty acid degradation - Homo sapiens (human);Long chain acyl-CoA dehydrogenase deficiency (LCAD);Trifunctional protein deficiency;Carnitine palmitoyl transferase deficiency (II);Very-long-chain acyl coa dehydrogenase deficiency (VLCAD);Medium chain acyl-coa dehydrogenase deficiency (MCAD);Short Chain Acyl CoA Dehydrogenase Deficiency (SCAD Deficiency);Fatty acid Metabolism;Glutaric Aciduria Type I;Ethylmalonic Encephalopathy;Carnitine palmitoyl transferase deficiency (I);Fatty Acid Beta Oxidation;XBP1(S) activates chaperone genes;Mitochondrial LC-Fatty Acid Beta-Oxidation;Liver steatosis AOP;Metabolism of lipids;mitochondrial fatty acid beta-oxidation of saturated fatty acids;Mitochondrial Fatty Acid Beta-Oxidation;Metabolism;Fatty acid metabolism;Beta oxidation of palmitoyl-CoA to myristoyl-CoA;FOXA2 and FOXA3 transcription factor networks (Consensus)

Recessive Scores

• pRec: 0.286

Intolerance Scores

• loftool: 0.0621
• rvis_EVS: 0.03
• rvis_percentile_EVS: 55.79

Haploinsufficiency Scores

• pHI: 0.0909
• hipred: N
• hipred_score: 0.196
• ghis: 0.434

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.802

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Acadvl
• Phenotype: muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype; neoplasm; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: acadvl
• Affected structure: head
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: temperature homeostasis;fatty acid beta-oxidation;response to cold;energy derivation by oxidation of organic compounds;epithelial cell differentiation;fatty acid beta-oxidation using acyl-CoA dehydrogenase;IRE1-mediated unfolded protein response;negative regulation of fatty acid biosynthetic process;negative regulation of fatty acid oxidation;regulation of cholesterol metabolic process
• Cellular component: nucleus;nucleolus;mitochondrion;mitochondrial inner membrane;mitochondrial matrix;cytosol;mitochondrial membrane;mitochondrial nucleoid
• Molecular function: fatty-acyl-CoA binding;acyl-CoA dehydrogenase activity;long-chain-acyl-CoA dehydrogenase activity;very-long-chain-acyl-CoA dehydrogenase activity;flavin adenine dinucleotide binding