ACADS

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

Basic information

Region (hg38): 12:120725773-120740008

Links

ENSG00000122971 ∙ NCBI:35 ∙ OMIM:606885 ∙ HGNC:90 ∙ Uniprot:P16219 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• short chain acyl-CoA dehydrogenase deficiency (Strong), mode of inheritance: AR
• short chain acyl-CoA dehydrogenase deficiency (Definitive), mode of inheritance: AR
• short chain acyl-CoA dehydrogenase deficiency (Supportive), mode of inheritance: AR
• short chain acyl-CoA dehydrogenase deficiency (Strong), mode of inheritance: AR
• short chain acyl-CoA dehydrogenase deficiency (Definitive), mode of inheritance: AR
• short 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, short-chain, deficiency of	AR	Biochemical	Clinical manifestations range from infantile acute acidosis and muscle weakness to chronic adult myopathy, and in the infantile forms, medical/dietary therapy (eg, IV glucose/carnitine in the initial phase, and low-fat, diet with MCT oil and carnitine and riboflavin, as well as avoidance of fasting) can be effective	Biochemical;Musculoskeletal; Neurologic	3571488; 3335634; 2808706; 7776094; 9266373; 9499414; 9578969; 9932958; 11134486; 11524729; 18523805; 18054510; 20376488; 20429031; 21325261; 21500142

ClinVar

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

• Deficiency of butyryl-CoA dehydrogenase (348 variants)
• not provided (91 variants)
• not specified (18 variants)
• ACADS-related condition (8 variants)
• Inborn genetic diseases (3 variants)
• See cases (3 variants)
• Type 2 diabetes mellitus (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ACADS 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			5	41	5	51
missense	3	22	120	7		152
nonsense	2	7	2			11
start loss	1	1				2
frameshift	7	17	2			26
inframe indel	1		10			11
splice donor/acceptor (+/-2bp)	1	12				13
splice region			9	7	1	17
non coding		1	17	33	18	69
Total	15	60	156	81	23

Highest pathogenic variant AF is 0.000532

Variants in ACADS

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

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

Position	Type	Phenotype	Significance	ClinVar
12-120725830-C-G		Deficiency of butyryl-CoA dehydrogenase	Uncertain significance (Jan 13, 2018)
12-120725830-C-T		Deficiency of butyryl-CoA dehydrogenase	Uncertain significance (Jan 13, 2018)
12-120725886-A-G		Deficiency of butyryl-CoA dehydrogenase	Conflicting classifications of pathogenicity (May 08, 2023)
12-120725887-T-C		Deficiency of butyryl-CoA dehydrogenase	Pathogenic/Likely pathogenic (Jun 06, 2023)
12-120725888-G-A		Deficiency of butyryl-CoA dehydrogenase	Pathogenic (Jan 22, 2024)
12-120725907-C-A		ACADS-related disorder	Likely benign (Oct 18, 2023)
12-120725913-T-TCGGGCCC		Deficiency of butyryl-CoA dehydrogenase	Likely pathogenic (Aug 29, 2017)
12-120725914-CG-C		Deficiency of butyryl-CoA dehydrogenase	Likely pathogenic (Jun 14, 2016)
12-120725923-C-T		Deficiency of butyryl-CoA dehydrogenase	Uncertain significance (Dec 26, 2023)
12-120725925-C-G		Deficiency of butyryl-CoA dehydrogenase	Uncertain significance (Sep 12, 2022)
12-120725926-G-A			Uncertain significance (Mar 21, 2023)
12-120725928-A-G		Deficiency of butyryl-CoA dehydrogenase	Uncertain significance (Apr 06, 2022)
12-120725934-G-C		Deficiency of butyryl-CoA dehydrogenase	Likely benign (Mar 26, 2024)
12-120725939-C-A		Deficiency of butyryl-CoA dehydrogenase	Likely benign (Nov 16, 2020)
12-120725940-G-T		Deficiency of butyryl-CoA dehydrogenase	Likely benign (Apr 29, 2023)
12-120725946-G-A		Deficiency of butyryl-CoA dehydrogenase	Likely benign (Sep 01, 2022)
12-120725947-A-C		Deficiency of butyryl-CoA dehydrogenase	Likely benign (Jun 07, 2022)
12-120725951-G-C		Deficiency of butyryl-CoA dehydrogenase	Likely benign (Sep 03, 2023)
12-120726849-C-T			Benign (Jul 21, 2018)
12-120727009-T-C		Deficiency of butyryl-CoA dehydrogenase	Likely benign (Oct 05, 2023)
12-120727012-G-C		Deficiency of butyryl-CoA dehydrogenase	Likely benign (Dec 02, 2021)
12-120727020-C-A		Deficiency of butyryl-CoA dehydrogenase	Uncertain significance (Oct 09, 2023)
12-120727024-A-C		Deficiency of butyryl-CoA dehydrogenase	Likely pathogenic (Sep 19, 2022)
12-120727026-C-T		Deficiency of butyryl-CoA dehydrogenase	Uncertain significance (Dec 18, 2023)
12-120727032-G-GT		Deficiency of butyryl-CoA dehydrogenase	Likely pathogenic (Mar 10, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ACADS	protein_coding	protein_coding	ENST00000242592	10	14274

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000280	0.929	125708	0	40	125748	0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.584	239	266	0.899	0.0000182	2650
Missense in Polyphen		117	131.42	0.89029		1266
Synonymous	0.319	113	117	0.963	0.00000936	845
Loss of Function	1.74	12	20.5	0.586	9.92e-7	223

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000494	0.000485
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000549	0.0000544
Finnish	0.000231	0.000231
European (Non-Finnish)	0.000141	0.000141
Middle Eastern	0.0000549	0.0000544
South Asian	0.000262	0.000261
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Introduces a double bond at position 2 in saturated acyl-CoA's of short chain length, i.e. less than 6 carbon atoms. {ECO:0000250|UniProtKB:P15651}.
• Disease: DISEASE: Acyl-CoA dehydrogenase short-chain deficiency (ACADSD) [MIM:201470]: An inborn error of mitochondrial fatty acid beta- oxidation resulting in acute acidosis and muscle weakness in infants, and a form of lipid-storage myopathy in adults. {ECO:0000269|PubMed:11134486, ECO:0000269|PubMed:1692038, ECO:0000269|PubMed:9499414}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Butanoate metabolism - Homo sapiens (human);Fatty acid degradation - Homo sapiens (human);Valine, leucine and isoleucine degradation - Homo sapiens (human);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;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;Mitochondrial Beta-Oxidation of Short Chain Saturated Fatty Acids;Short-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (SCHAD);Methylmalonic Aciduria;3-Methylglutaconic Aciduria Type IV;3-Methylglutaconic Aciduria Type III;Butyrate Metabolism;Beta-Ketothiolase Deficiency;Carnitine palmitoyl transferase deficiency (I);Fatty Acid Beta Oxidation;Mitochondrial LC-Fatty Acid Beta-Oxidation;Liver steatosis AOP;Butanoate metabolism;Metabolism of lipids;Beta oxidation of hexanoyl-CoA to butanoyl-CoA;Beta oxidation of butanoyl-CoA to acetyl-CoA;mitochondrial fatty acid beta-oxidation of saturated fatty acids;Mitochondrial Fatty Acid Beta-Oxidation;Saturated fatty acids beta-oxidation;Metabolism;Fatty acid metabolism;Valine, leucine and isoleucine degradation;Butanoate metabolism;Valine Leucine Isoleucine degradation (Consensus)

Recessive Scores

• pRec: 0.526

Intolerance Scores

• loftool: 0.196
• rvis_EVS: -0.2
• rvis_percentile_EVS: 39.11

Haploinsufficiency Scores

• pHI: 0.217
• hipred: N
• hipred_score: 0.401
• ghis: 0.497

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.709

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Acads
• Phenotype: renal/urinary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands 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); muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: fatty acid beta-oxidation;fatty acid beta-oxidation using acyl-CoA dehydrogenase;butyrate catabolic process
• Cellular component: nucleus;nucleoplasm;mitochondrion;mitochondrial matrix
• Molecular function: acyl-CoA dehydrogenase activity;butyryl-CoA dehydrogenase activity;flavin adenine dinucleotide binding