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 (1916 variants)
not_provided (254 variants)
not_specified (128 variants)
Inborn_genetic_diseases (104 variants)
ACADVL-related_disorder (60 variants)
Rhabdomyolysis (4 variants)
Abnormality_of_the_musculature (3 variants)
Abnormal_circulating_enzyme_concentration (2 variants)
See_cases (2 variants)
Myopathy (2 variants)
Cardiac_arrhythmia (1 variants)
Primary_dilated_cardiomyopathy (1 variants)
Pancreatic_hypoplasia-diabetes-congenital_heart_disease_syndrome (1 variants)
Pearson_syndrome (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. These statistics are base on transcript: NM_000000018.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous	2 clinvar	7 clinvar	23 clinvar	375 clinvar	4 clinvar	411
missense	27 clinvar	207 clinvar	484 clinvar	7 clinvar	5 clinvar	730
nonsense	24 clinvar	24 clinvar	3 clinvar			51
start loss		1				1
frameshift	71 clinvar	120 clinvar	5 clinvar			196
splice donor/acceptor (+/-2bp)	19 clinvar	69 clinvar	4 clinvar	1 clinvar		93
Total	143	428	519	383	9

Highest pathogenic variant AF is 0.0015937401

Loading clinvar variants...

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