ACAD8

acyl-CoA dehydrogenase family member 8, the group of Acyl-CoA dehydrogenase family

Basic information

Region (hg38): 11:134253548-134265855

Links

ENSG00000151498 ∙ NCBI:27034 ∙ OMIM:604773 ∙ HGNC:87 ∙ Uniprot:Q9UKU7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• isobutyryl-CoA dehydrogenase deficiency (Strong), mode of inheritance: AR
• isobutyryl-CoA dehydrogenase deficiency (Strong), mode of inheritance: AR
• isobutyryl-CoA dehydrogenase deficiency (Supportive), mode of inheritance: AR
• isobutyryl-CoA dehydrogenase deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Isobutyryl-CoA dehydrogenase deficiency	AR	Biochemical	Metabolic precautions may be beneficial to prevent and treat acute decompensation; Medical treatment (eg, with oral L-carnitine) has been reported as allowing growth catch-up and normalization of cardiac status	Biochemical; Cardiovascular; Hematologic; Musculoskeletal; Neurologic	9889013; 12359132; 17304052; 16857760; 17924841; 21290185; 22241096

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ACAD8 gene.

• Deficiency of isobutyryl-CoA dehydrogenase (10 variants)
• not provided (4 variants)
• Inborn genetic diseases (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ACAD8 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			7	22	1	30
missense	4	5	84	4	1	98
nonsense	5	1				6
start loss		4				4
frameshift	3					3
inframe indel						0
splice donor/acceptor (+/-2bp)	3	3	2			8
splice region			6	6	2	14
non coding			18	15	37	70
Total	15	13	111	41	39

Highest pathogenic variant AF is 0.0000460

Variants in ACAD8

This is a list of pathogenic ClinVar variants found in the ACAD8 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-134253601-A-G		Deficiency of isobutyryl-CoA dehydrogenase	Likely pathogenic (Jan 03, 2024)
11-134253602-T-C		Deficiency of isobutyryl-CoA dehydrogenase	Likely pathogenic (Jun 20, 2022)
11-134253603-G-C		Deficiency of isobutyryl-CoA dehydrogenase	Likely pathogenic (Aug 02, 2022)
11-134253603-G-T			Likely pathogenic (Feb 17, 2016)
11-134253612-C-T		Deficiency of isobutyryl-CoA dehydrogenase	Likely benign (Jul 23, 2022)
11-134253620-G-C		not specified • Deficiency of isobutyryl-CoA dehydrogenase	Benign (Jan 19, 2024)
11-134253627-C-T		Deficiency of isobutyryl-CoA dehydrogenase	Likely benign (Oct 06, 2020)
11-134253632-C-T		Deficiency of isobutyryl-CoA dehydrogenase	Uncertain significance (Oct 31, 2022)
11-134253636-C-G			Likely benign (May 24, 2018)
11-134253645-CCTGCCCG-C			Pathogenic (Mar 24, 2015)
11-134253664-G-T		Deficiency of isobutyryl-CoA dehydrogenase	Uncertain significance (Feb 28, 2020)
11-134253679-G-A		Deficiency of isobutyryl-CoA dehydrogenase	Uncertain significance (Dec 08, 2021)
11-134253683-A-G		Inborn genetic diseases	Likely benign (Jul 26, 2022)
11-134253685-C-T		Deficiency of isobutyryl-CoA dehydrogenase	Uncertain significance (Dec 02, 2020)
11-134253699-C-T		Deficiency of isobutyryl-CoA dehydrogenase	Uncertain significance (Jan 12, 2018)
11-134253704-T-G		Deficiency of isobutyryl-CoA dehydrogenase	Uncertain significance (Jun 21, 2022)
11-134253709-C-T		Deficiency of isobutyryl-CoA dehydrogenase	Uncertain significance (Aug 19, 2022)
11-134253728-G-T		Deficiency of isobutyryl-CoA dehydrogenase	Uncertain significance (Aug 24, 2023)
11-134253842-G-C			Likely benign (Jun 14, 2018)
11-134253968-C-A			Benign (Jun 18, 2021)
11-134256374-A-G			Likely benign (Jun 14, 2018)
11-134256531-T-C		Deficiency of isobutyryl-CoA dehydrogenase	Likely benign (Aug 27, 2023)
11-134256535-A-G		Deficiency of isobutyryl-CoA dehydrogenase	Uncertain significance (Jan 13, 2018)
11-134256539-T-C		Deficiency of isobutyryl-CoA dehydrogenase	Conflicting classifications of pathogenicity (Jan 18, 2024)
11-134256542-C-T		Deficiency of isobutyryl-CoA dehydrogenase	Uncertain significance (Jan 13, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ACAD8	protein_coding	protein_coding	ENST00000281182	11	12361

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.64e-14	0.0553	125678	0	70	125748	0.000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.222	221	231	0.959	0.0000132	2701
Missense in Polyphen		89	93.727	0.94956		1080
Synonymous	-1.95	115	91.3	1.26	0.00000562	823
Loss of Function	0.508	22	24.7	0.890	0.00000156	246

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000561	0.000561
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000350	0.000334
Middle Eastern	0.000163	0.000163
South Asian	0.000327	0.000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Has very high activity toward isobutyryl-CoA. Is an isobutyryl-CoA dehydrogenase that functions in valine catabolism. Plays a role in transcriptional coactivation within the ARC complex. {ECO:0000269|PubMed:12359132}.
• Pathway: Valine, leucine and isoleucine degradation - Homo sapiens (human);3-Methylglutaconic Aciduria Type I;Valine, Leucine and Isoleucine Degradation;2-Methyl-3-Hydroxybutryl CoA Dehydrogenase Deficiency;Isovaleric Aciduria;3-Methylcrotonyl Coa Carboxylase Deficiency Type I;Propionic Acidemia;Maple Syrup Urine Disease;3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency;Isobutyryl-coa dehydrogenase deficiency;3-hydroxyisobutyric aciduria;3-hydroxyisobutyric acid dehydrogenase deficiency;Isovaleric acidemia;Methylmalonate Semialdehyde Dehydrogenase Deficiency;Methylmalonic Aciduria;3-Methylglutaconic Aciduria Type IV;3-Methylglutaconic Aciduria Type III;Beta-Ketothiolase Deficiency;Branched-chain amino acid catabolism;Metabolism of amino acids and derivatives;Metabolism;valine degradation (Consensus)

Recessive Scores

• pRec: 0.250

Intolerance Scores

• loftool: 0.287
• rvis_EVS: -0.38
• rvis_percentile_EVS: 27.88

Haploinsufficiency Scores

• pHI: 0.0217
• hipred: N
• hipred_score: 0.289
• ghis: 0.530

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.992

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Acad8
• Phenotype: adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype; liver/biliary system phenotype; renal/urinary system phenotype

Gene ontology

• Biological process: valine catabolic process;lipid metabolic process;branched-chain amino acid catabolic process;oxidation-reduction process
• Cellular component: mitochondrial matrix
• Molecular function: acyl-CoA dehydrogenase activity;flavin adenine dinucleotide binding