ACADSB

acyl-CoA dehydrogenase short/branched chain, the group of Acyl-CoA dehydrogenase family

Basic information

Region (hg38): 10:123008979-123058290

Links

ENSG00000196177 ∙ NCBI:36 ∙ OMIM:600301 ∙ HGNC:91 ∙ Uniprot:P45954 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

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

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
2-methylbutyryl-CoA dehydrogenase deficiency	AR	General	The clinical relevance of the condition is unclear, though some have stated that special attention may be necessary in situations involving potential metabolic decompensation	Biochemical	10832746; 12837870; 16317551; 17883863; 17945527; 20547083; 21290185

ClinVar

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

• Deficiency_of_2-methylbutyryl-CoA_dehydrogenase (167 variants)
• not_provided (29 variants)
• ACADSB-related_disorder (17 variants)
• not_specified (8 variants)
• Inborn_genetic_diseases (4 variants)
• See_cases (2 variants)
• Microcephaly (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ACADSB gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001609.4. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	28	5	36
missense	5	4	71	4	1	85
nonsense	1	7				8
start loss			1			1
frameshift	3	9				12
splice donor/acceptor (+/-2bp)	2	9				11
Total	11	29	75	32	6

Highest pathogenic variant AF is 0.000778146

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ACADSB	protein_coding	protein_coding	ENST00000358776	11	49333

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.66e-11	0.263	125537	0	211	125748	0.000839

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0697	230	227	1.01	0.0000110	2789
Missense in Polyphen		89	91.567	0.97197		1143
Synonymous	0.538	78	84.3	0.925	0.00000447	818
Loss of Function	0.910	19	23.8	0.799	0.00000109	312

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00309	0.00309
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00272	0.00272
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000757	0.000756
Middle Eastern	0.00272	0.00272
South Asian	0.000196	0.000196
Other	0.000816	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Has greatest activity toward short branched chain acyl- CoA derivative such as (s)-2-methylbutyryl-CoA, isobutyryl-CoA, and 2-methylhexanoyl-CoA as well as toward short straight chain acyl-CoAs such as butyryl-CoA and hexanoyl-CoA. Can use valproyl- CoA as substrate and may play a role in controlling the metabolic flux of valproic acid in the development of toxicity of this agent.
• Pathway: Fatty acid degradation - Homo sapiens (human);Valine, leucine and isoleucine degradation - Homo sapiens (human);Valproic Acid Pathway, Pharmacokinetics;Long chain acyl-CoA dehydrogenase deficiency (LCAD);3-Methylglutaconic Aciduria Type I;Valine, Leucine and Isoleucine Degradation;2-Methyl-3-Hydroxybutryl CoA Dehydrogenase Deficiency;Trifunctional protein deficiency;Carnitine palmitoyl transferase deficiency (II);Very-long-chain acyl coa dehydrogenase deficiency (VLCAD);Medium chain acyl-coa dehydrogenase deficiency (MCAD);Isovaleric Aciduria;3-Methylcrotonyl Coa Carboxylase Deficiency Type I;Propionic Acidemia;Short Chain Acyl CoA Dehydrogenase Deficiency (SCAD Deficiency);Fatty acid Metabolism;Maple Syrup Urine Disease;Valproic Acid Metabolism Pathway;3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency;Isobutyryl-coa dehydrogenase deficiency;3-hydroxyisobutyric aciduria;3-hydroxyisobutyric acid dehydrogenase deficiency;Isovaleric acidemia;Glutaric Aciduria Type I;Ethylmalonic Encephalopathy;Methylmalonate Semialdehyde Dehydrogenase Deficiency;Methylmalonic Aciduria;3-Methylglutaconic Aciduria Type IV;3-Methylglutaconic Aciduria Type III;Beta-Ketothiolase Deficiency;Carnitine palmitoyl transferase deficiency (I);Valproic acid pathway;Branched-chain amino acid catabolism;Metabolism of amino acids and derivatives;Saturated fatty acids beta-oxidation;Metabolism;Mono-unsaturated fatty acid beta-oxidation;Valine, leucine and isoleucine degradation;Propanoate metabolism;Dimethyl-branched-chain fatty acid mitochondrial beta-oxidation;isoleucine degradation (Consensus)

Recessive Scores

• pRec: 0.275

Intolerance Scores

• loftool: 0.294
• rvis_EVS: -0.4
• rvis_percentile_EVS: 26.73

Haploinsufficiency Scores

• pHI: 0.507
• hipred: N
• hipred_score: 0.197
• ghis: 0.472

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.872

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Acadsb

Gene ontology

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