ACADM

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

Basic information

Region (hg38): 1:75724431-75787575

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 (859 variants)
not_provided (166 variants)
not_specified (57 variants)
Inborn_genetic_diseases (52 variants)
ACADM-related_disorder (29 variants)
See_cases (6 variants)
Epileptic_spasm (2 variants)
Hydrocephalus,_nonsyndromic,_autosomal_recessive_2 (1 variants)
MCADD_-_Medium-chain_acyl-CoA_dehydrogenase_deficiency_?_full_ACADM_sequencing_newborn_screening_follow_up (1 variants)
Deficiency_of_butyryl-CoA_dehydrogenase (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. These statistics are base on transcript: NM_000000016.6. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			13 clinvar	144 clinvar	2 clinvar	159
missense	24 clinvar	135 clinvar	188 clinvar	3 clinvar	1 clinvar	351
nonsense	29 clinvar	22 clinvar				51
start loss	3	2				5
frameshift	54 clinvar	46 clinvar				100
splice donor/acceptor (+/-2bp)	16 clinvar	36 clinvar	5 clinvar	1 clinvar		58
Total	126	241	206	148	3

Highest pathogenic variant AF is 0.00582253

Loading clinvar variants...

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