ACADL

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

Basic information

Region (hg38): 2:210187126-210225447

Links

ENSG00000115361 ∙ NCBI:33 ∙ OMIM:609576 ∙ HGNC:88 ∙ Uniprot:P28330 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• long chain acyl-CoA dehydrogenase deficiency (Disputed Evidence), mode of inheritance: AR

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ACADL 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				6	2	8
missense			24	2	2	28
nonsense						0
start loss						0
frameshift			3			3
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region				2	1	3
non coding			1	2		3
Total	0	0	29	10	4

Variants in ACADL

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

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

Position	Type	Phenotype	Significance	ClinVar
2-210188340-C-T		Very long chain acyl-CoA dehydrogenase deficiency	Uncertain significance (Jun 14, 2016)
2-210192795-T-C		ACADL-related disorder	Likely benign (May 24, 2022)
2-210192818-C-G		not specified	Uncertain significance (Mar 20, 2023)
2-210192853-C-T		not specified	Uncertain significance (May 02, 2024)
2-210195206-C-T		ACADL-related disorder	Likely benign (Aug 10, 2019)
2-210195219-C-T		ACADL-related disorder	Likely benign (May 13, 2021)
2-210195220-G-A		not specified	Uncertain significance (Mar 07, 2023)
2-210195224-T-C		not specified	Uncertain significance (Aug 09, 2021)
2-210195289-C-T		not specified	Uncertain significance (Jun 17, 2022)
2-210195326-T-G			Benign (Nov 09, 2023)
2-210195331-T-C		not specified	Uncertain significance (Aug 16, 2021)
2-210203359-G-A		not specified	Uncertain significance (Jan 31, 2024)
2-210203376-A-G		ACADL-related disorder	Likely benign (Jul 01, 2022)
2-210203382-CCTGGT-AAACATAACATTCATG		Very long chain acyl-CoA dehydrogenase deficiency	Conflicting classifications of pathogenicity (Oct 01, 2021)
2-210203383-C-A			Benign (Nov 01, 2023)
2-210203385-GGT-G			Uncertain significance (Nov 01, 2023)
2-210203393-C-T		not specified	Uncertain significance (Feb 01, 2024)
2-210203405-C-G		not specified	Uncertain significance (Jul 30, 2023)
2-210203444-C-T		not specified	Uncertain significance (Aug 09, 2021)
2-210203446-T-C		ACADL-related disorder	Uncertain significance (Aug 16, 2023)
2-210204571-C-T		ACADL-related disorder	Likely benign (Feb 27, 2019)
2-210204606-T-C		ACADL-related disorder	Uncertain significance (Mar 20, 2024)
2-210204643-C-A		not specified	Uncertain significance (Sep 20, 2023)
2-210204652-G-A		Long chain acyl-CoA dehydrogenase deficiency	Conflicting classifications of pathogenicity (Aug 01, 2023)
2-210205678-C-G		not specified • Long chain acyl-CoA dehydrogenase deficiency	Conflicting classifications of pathogenicity (Mar 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ACADL	protein_coding	protein_coding	ENST00000233710	11	37553

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.74e-12	0.202	125577	0	170	125747	0.000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.856	196	233	0.842	0.0000114	2797
Missense in Polyphen		74	81.338	0.90979		1044
Synonymous	1.79	61	81.5	0.748	0.00000418	815
Loss of Function	0.913	21	26.0	0.807	0.00000132	300

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000920	0.000919
Ashkenazi Jewish	0.000596	0.000595
East Asian	0.000381	0.000381
Finnish	0.00	0.00
European (Non-Finnish)	0.000811	0.000809
Middle Eastern	0.000381	0.000381
South Asian	0.000850	0.000850
Other	0.00229	0.00228

dbNSFP

Source: dbNSFP

• Pathway: Fatty acid degradation - Homo sapiens (human);PPAR signaling pathway - 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;Mitochondrial Beta-Oxidation of Short Chain Saturated Fatty Acids;Mitochondrial Beta-Oxidation of Long Chain Saturated Fatty Acids;Short-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (SCHAD);Carnitine palmitoyl transferase deficiency (I);Fatty Acid Beta Oxidation;Mitochondrial LC-Fatty Acid Beta-Oxidation;PPAR signaling pathway;Liver steatosis AOP;Metabolism of lipids;Beta oxidation of myristoyl-CoA to lauroyl-CoA;mitochondrial fatty acid beta-oxidation of saturated fatty acids;Mitochondrial Fatty Acid Beta-Oxidation;Saturated fatty acids beta-oxidation;Metabolism;Fatty acid metabolism;Mono-unsaturated fatty acid beta-oxidation;Valine, leucine and isoleucine degradation;Propanoate metabolism;Dimethyl-branched-chain fatty acid mitochondrial beta-oxidation;Di-unsaturated fatty acid beta-oxidation;fatty acid β-oxidation;Beta oxidation of lauroyl-CoA to decanoyl-CoA-CoA (Consensus)

Recessive Scores

• pRec: 0.326

Intolerance Scores

• loftool: 0.344
• rvis_EVS: -0.36
• rvis_percentile_EVS: 29.16

Haploinsufficiency Scores

• pHI: 0.0672
• hipred: N
• hipred_score: 0.397
• ghis: 0.500

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.296

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Acadl
• Phenotype: 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); reproductive system phenotype; 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); liver/biliary system phenotype; renal/urinary system phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: temperature homeostasis;fatty acid beta-oxidation;carnitine metabolic process, CoA-linked;fatty acid beta-oxidation using acyl-CoA dehydrogenase;carnitine catabolic process;long-chain fatty acid catabolic process;cellular lipid catabolic process;negative regulation of fatty acid biosynthetic process;negative regulation of fatty acid oxidation;protein homotetramerization;oxidation-reduction process;regulation of cholesterol metabolic process;positive regulation of cold-induced thermogenesis
• Cellular component: mitochondrion;mitochondrial matrix;mitochondrial membrane
• Molecular function: fatty-acyl-CoA binding;acyl-CoA dehydrogenase activity;long-chain-acyl-CoA dehydrogenase activity;palmitoyl-CoA oxidase activity;flavin adenine dinucleotide binding