ACADM

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

Basic information

Region (hg38): 1:75724430-75787575

Links

ENSG00000117054 ∙ NCBI:34 ∙ OMIM:607008 ∙ HGNC:89 ∙ Uniprot:P11310 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• medium chain acyl-CoA dehydrogenase deficiency (Definitive), mode of inheritance: AR
• medium chain acyl-CoA dehydrogenase deficiency (Strong), mode of inheritance: AR
• medium chain acyl-CoA dehydrogenase deficiency (Strong), mode of inheritance: AR
• medium chain acyl-CoA dehydrogenase deficiency (Supportive), mode of inheritance: AR
• medium 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, medium chain, deficiency of	AR	Biochemical	Dietary treatment (eg, with frequent feedings in infancy, and low-fat diet for toddlers, as well as bedtime administration of uncooked cornstarch to avoid overnight hypoglycemia); In order to avoid/treat catabolism, simple oral (or IV if necessary) carbohydrates can be effective; Fasting should be avoided, as should infant formulas whose primary fat source is medium-chain triglycerides	Biochemical; Musculoskeletal; Neurologic	947635; 6402754; 6857268; 6646897; 3462713; 3944676; 3822638; 2502671; 2393404; 1361190; 8120710; 7603790; 9158144; 11349232; 11524729; 11409868; 15915086; 15832312; 19780764; 20923556; 20434380; 21239873; 20301597; 23574375

ClinVar

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

• Medium-chain acyl-coenzyme A dehydrogenase deficiency (661 variants)
• not provided (178 variants)
• not specified (52 variants)
• Inborn genetic diseases (32 variants)
• ACADM-related condition (13 variants)
• See cases (4 variants)
• Epileptic spasm (2 variants)
• Abnormal circulating lipid concentration (2 variants)
• Medium chain dicarboxylic aciduria (2 variants)
• MCAD deficiency, modifier of (1 variants)
• Hydrocephalus, nonsyndromic, autosomal recessive 2 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ACADM 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			2	106	5	113
missense	21	77	119	4	1	222
nonsense	16	20	1			37
start loss	2	3				5
frameshift	39	35				74
inframe indel	1	2	9			12
splice donor/acceptor (+/-2bp)	12	30	2	1		45
splice region		1	11	26	1	39
non coding		2	21	62	38	123
Total	91	169	154	173	44

Highest pathogenic variant AF is 0.0000263

Variants in ACADM

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

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

Position	Type	Phenotype	Significance	ClinVar
1-75724446-G-T		Medium-chain acyl-coenzyme A dehydrogenase deficiency	Uncertain significance (Jun 14, 2016)
1-75724484-A-G		Medium-chain acyl-coenzyme A dehydrogenase deficiency	Uncertain significance (Jun 14, 2016)
1-75724531-G-A		Medium-chain acyl-coenzyme A dehydrogenase deficiency	Benign/Likely benign (Jul 01, 2021)
1-75724619-C-T		Medium-chain acyl-coenzyme A dehydrogenase deficiency	Uncertain significance (Jun 14, 2016)
1-75724646-C-G		Medium-chain acyl-coenzyme A dehydrogenase deficiency	Benign/Likely benign (Jun 14, 2016)
1-75724696-A-G		Medium-chain acyl-coenzyme A dehydrogenase deficiency	Uncertain significance (Jun 14, 2016)
1-75724710-G-C		Medium-chain acyl-coenzyme A dehydrogenase deficiency	Uncertain significance (Jan 13, 2018)
1-75724738-A-T		Medium-chain acyl-coenzyme A dehydrogenase deficiency	Uncertain significance (Jun 14, 2016)
1-75724754-T-C		not specified • Medium-chain acyl-coenzyme A dehydrogenase deficiency	Benign (Nov 15, 2018)
1-75724759-T-C		Medium-chain acyl-coenzyme A dehydrogenase deficiency	Uncertain significance (Jan 12, 2018)
1-75724771-C-G		Medium-chain acyl-coenzyme A dehydrogenase deficiency	Uncertain significance (Aug 17, 2017)
1-75724782-GCCAACATGGCA-ACCCCGAGTG		Medium-chain acyl-coenzyme A dehydrogenase deficiency	Pathogenic/Likely pathogenic (Oct 11, 2022)
1-75724788-A-G		Medium-chain acyl-coenzyme A dehydrogenase deficiency	Pathogenic/Likely pathogenic (Sep 21, 2023)
1-75724788-A-T		Medium-chain acyl-coenzyme A dehydrogenase deficiency	Pathogenic (Apr 23, 2021)
1-75724789-T-G		Medium-chain acyl-coenzyme A dehydrogenase deficiency	Pathogenic (Sep 17, 2023)
1-75724790-G-C		Medium-chain acyl-coenzyme A dehydrogenase deficiency	Pathogenic/Likely pathogenic (Dec 01, 2022)
1-75724793-A-C		Medium-chain acyl-coenzyme A dehydrogenase deficiency	Likely benign (Jan 29, 2024)
1-75724793-A-G		Medium-chain acyl-coenzyme A dehydrogenase deficiency	Likely benign (Nov 10, 2021)
1-75724793-A-T		Medium-chain acyl-coenzyme A dehydrogenase deficiency	Likely benign (May 17, 2021)
1-75724797-G-A		Medium-chain acyl-coenzyme A dehydrogenase deficiency	Uncertain significance (Apr 15, 2022)
1-75724798-G-T		Medium-chain acyl-coenzyme A dehydrogenase deficiency	Uncertain significance (Aug 02, 2022)
1-75724799-G-A		Medium-chain acyl-coenzyme A dehydrogenase deficiency	Likely benign (Aug 28, 2023)
1-75724799-G-C		Medium-chain acyl-coenzyme A dehydrogenase deficiency	Likely benign (Nov 04, 2023)
1-75724799-G-T		Medium-chain acyl-coenzyme A dehydrogenase deficiency • ACADM-related disorder	Likely benign (Dec 05, 2023)
1-75724802-C-A		Medium-chain acyl-coenzyme A dehydrogenase deficiency	Uncertain significance (Jul 18, 2017)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ACADM	protein_coding	protein_coding	ENST00000420607	12	63225

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.05e-12	0.221	125669	0	78	125747	0.000310

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.543	205	228	0.899	0.0000114	2766
Missense in Polyphen		56	70.086	0.79902		844
Synonymous	0.163	70	71.8	0.976	0.00000351	798
Loss of Function	0.947	21	26.2	0.801	0.00000132	322

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000666	0.000666
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000435	0.000435
Finnish	0.0000925	0.0000924
European (Non-Finnish)	0.000317	0.000316
Middle Eastern	0.000435	0.000435
South Asian	0.000523	0.000523
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acyl-CoA dehydrogenase specific for acyl chain lengths of 4 to 16 that catalyzes the initial step of fatty acid beta- oxidation. Utilizes the electron transfer flavoprotein (ETF) as an electron acceptor to transfer electrons to the main mitochondrial respiratory chain via ETF-ubiquinone oxidoreductase (ETF dehydrogenase). {ECO:0000269|PubMed:25416781}.
• Disease: DISEASE: Acyl-CoA dehydrogenase medium-chain deficiency (ACADMD) [MIM:201450]: An inborn error of mitochondrial fatty acid beta- oxidation which causes fasting hypoglycemia, hepatic dysfunction and encephalopathy, often resulting in death in infancy. {ECO:0000269|PubMed:10767181, ECO:0000269|PubMed:11349232, ECO:0000269|PubMed:11409868, ECO:0000269|PubMed:11486912, ECO:0000269|PubMed:1363805, ECO:0000269|PubMed:1671131, ECO:0000269|PubMed:1684086, ECO:0000269|PubMed:1902818, ECO:0000269|PubMed:2251268, ECO:0000269|PubMed:2393404, ECO:0000269|PubMed:2394825, ECO:0000269|PubMed:7603790, ECO:0000269|PubMed:7929823, ECO:0000269|PubMed:8198141, ECO:0000269|PubMed:9158144, ECO:0000269|PubMed:9882619}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: beta-Alanine metabolism - Homo sapiens (human);Propanoate metabolism - Homo sapiens (human);Fatty acid degradation - Homo sapiens (human);PPAR signaling pathway - 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;Malonyl-coa decarboxylase deficiency;Trifunctional protein deficiency;Carnitine palmitoyl transferase deficiency (II);Very-long-chain acyl coa dehydrogenase deficiency (VLCAD);Medium chain acyl-coa dehydrogenase deficiency (MCAD);Malonic Aciduria;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;Propanoate Metabolism;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 Medium Chain Saturated Fatty Acids;Methylmalonic Aciduria;Methylmalonic Aciduria Due to Cobalamin-Related Disorders;3-Methylglutaconic Aciduria Type IV;3-Methylglutaconic Aciduria Type III;Beta-Ketothiolase Deficiency;Carnitine palmitoyl transferase deficiency (I);Fatty Acid Beta Oxidation;Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha);PPAR Alpha Pathway;Nuclear Receptors Meta-Pathway;Mitochondrial LC-Fatty Acid Beta-Oxidation;Amino Acid metabolism;PPAR signaling pathway;Liver steatosis AOP;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Metabolism of lipids;Beta oxidation of decanoyl-CoA to octanoyl-CoA-CoA;Beta oxidation of octanoyl-CoA to hexanoyl-CoA;mitochondrial fatty acid beta-oxidation of saturated fatty acids;mitochondrial fatty acid beta-oxidation of unsaturated fatty acids;Mitochondrial Fatty Acid Beta-Oxidation;Saturated fatty acids beta-oxidation;Metabolism;Fatty acid metabolism;Propanoate metabolism;Mono-unsaturated fatty acid beta-oxidation;Valine, leucine and isoleucine degradation;Propanoate metabolism;Dimethyl-branched-chain fatty acid mitochondrial beta-oxidation;Valine Leucine Isoleucine degradation;FOXA2 and FOXA3 transcription factor networks (Consensus)

Recessive Scores

• pRec: 0.722

Intolerance Scores

• loftool: 0.155
• rvis_EVS: -0.25
• rvis_percentile_EVS: 35.99

Haploinsufficiency Scores

• pHI: 0.157
• hipred: N
• hipred_score: 0.338
• ghis: 0.565

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.994

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Acadm
• Phenotype: homeostasis/metabolism phenotype; muscle 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); 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

Gene ontology

• Biological process: fatty acid beta-oxidation;regulation of lipid metabolic process;carnitine metabolic process, CoA-linked;fatty acid beta-oxidation using acyl-CoA dehydrogenase;carnitine biosynthetic process;medium-chain fatty acid metabolic process;medium-chain fatty acid catabolic process;oxidation-reduction process
• Cellular component: nucleus;mitochondrion;mitochondrial matrix;nuclear speck;axon;mitochondrial membrane
• Molecular function: acyl-CoA dehydrogenase activity;identical protein binding;flavin adenine dinucleotide binding;medium-chain-acyl-CoA dehydrogenase activity