ACADM

Summary

ACADM (acyl-CoA dehydrogenase medium chain, HGNC:89) is a protein-coding gene on chromosome 1p31.1, encoding Medium-chain specific acyl-CoA dehydrogenase, mitochondrial (P11310). Medium-chain specific acyl-CoA dehydrogenase is one of the acyl-CoA dehydrogenases that catalyze the first step of mitochondrial fatty acid beta-oxidation (FAO), breaking down fatty acids into acetyl-CoA and allowing the production of energy from fats.

This gene encodes the medium-chain specific (C4 to C12 straight chain) acyl-Coenzyme A dehydrogenase. The homotetramer enzyme catalyzes the initial step of the mitochondrial fatty acid beta-oxidation pathway. Defects in this gene cause medium-chain acyl-CoA dehydrogenase deficiency, a disease characterized by hepatic dysfunction, fasting hypoglycemia, and encephalopathy, which can result in infantile death. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 34 — RefSeq curated summary.

At a glance

• Gene–disease (curated): medium chain acyl-CoA dehydrogenase deficiency (Definitive, ClinGen)
• GWAS associations: 28
• Clinical variants (ClinVar): 1,114 total — 127 pathogenic, 161 likely-pathogenic
• Phenotypes (HPO): 48
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_000016

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:89
Approved symbol	ACADM
Name	acyl-CoA dehydrogenase medium chain
Location	1p31.1
Locus type	gene with protein product
Status	Approved
Aliases	MCAD, MCADH, ACAD1
Ensembl gene	ENSG00000117054
Ensembl biotype	protein_coding
OMIM	607008
Entrez	34

Gene structure

Transcript identifiers

Ensembl transcripts: 76 — 33 nonsense_mediated_decay, 23 protein_coding, 19 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000370834, ENST00000370841, ENST00000420607, ENST00000473018, ENST00000481374, ENST00000525808, ENST00000525881, ENST00000526129, ENST00000526196, ENST00000526930, ENST00000528016, ENST00000529059, ENST00000530953, ENST00000532207, ENST00000532509, ENST00000534146, ENST00000534334, ENST00000541113, ENST00000679509, ENST00000679530, ENST00000679615, ENST00000679687, ENST00000679704, ENST00000679709, ENST00000679804, ENST00000679976, ENST00000680166, ENST00000680315, ENST00000680517, ENST00000680582, ENST00000680613, ENST00000680662, ENST00000680691, ENST00000680694, ENST00000680743, ENST00000680749, ENST00000680798, ENST00000680805, ENST00000680844, ENST00000680948, ENST00000680964, ENST00000681037, ENST00000681063, ENST00000681209, ENST00000681278, ENST00000681289, ENST00000681361, ENST00000681430, ENST00000681446, ENST00000681450, ENST00000681548, ENST00000681616, ENST00000681621, ENST00000681680, ENST00000681720, ENST00000681730, ENST00000681790, ENST00000681837, ENST00000681913, ENST00000681916, ENST00000681930, ENST00000879987, ENST00000879988, ENST00000879989, ENST00000879990, ENST00000879991, ENST00000879992, ENST00000879993, ENST00000879994, ENST00000879995, ENST00000879996, ENST00000879997, ENST00000927351, ENST00000927352, ENST00000927353, ENST00000956292

RefSeq mRNA: 5 — MANE Select: NM_000016 NM_000016, NM_001127328, NM_001286042, NM_001286043, NM_001286044

CCDS: CCDS44165, CCDS668, CCDS72807

Canonical transcript exons

ENST00000370841 — 12 exons

Exon	Start	End
ENSE00003495277	75750451	75750546
ENSE00003533043	75749419	75749559
ENSE00003600551	75732644	75732741
ENSE00003604105	75745806	75745914
ENSE00003619848	75733528	75733628
ENSE00003640977	75739980	75740110
ENSE00003643069	75732853	75732922
ENSE00003661831	75728401	75728488
ENSE00003667756	75734791	75734871
ENSE00003668352	75761122	75761370
ENSE00003899874	75724709	75724817
ENSE00003900114	75762692	75763679

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 99.27.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 34.8892 / max 553.9949, expressed in 1802 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
3544	34.2486	1800
3542	0.4104	205
3543	0.2302	107

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	99.27	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.13	gold quality
biceps brachii	UBERON:0001507	99.08	gold quality
heart right ventricle	UBERON:0002080	98.98	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.85	gold quality
body of tongue	UBERON:0011876	98.65	gold quality
jejunum	UBERON:0002115	98.64	gold quality
vastus lateralis	UBERON:0001379	98.62	gold quality
renal medulla	UBERON:0000362	98.61	gold quality
nephron tubule	UBERON:0001231	98.44	gold quality
upper leg skin	UBERON:0004262	98.39	gold quality
quadriceps femoris	UBERON:0001377	98.36	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	98.10	gold quality
adrenal tissue	UBERON:0018303	98.03	gold quality
muscle organ	UBERON:0001630	98.02	gold quality
gastrocnemius	UBERON:0001388	97.98	gold quality
skeletal muscle tissue	UBERON:0001134	97.95	gold quality
muscle of leg	UBERON:0001383	97.94	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.93	gold quality
cardiac ventricle	UBERON:0002082	97.92	gold quality
heart left ventricle	UBERON:0002084	97.88	gold quality
myocardium	UBERON:0002349	97.75	gold quality
diaphragm	UBERON:0001103	97.62	gold quality
duodenum	UBERON:0002114	97.62	gold quality
choroid plexus epithelium	UBERON:0003911	97.50	gold quality
left ventricle myocardium	UBERON:0006566	97.42	gold quality
kidney epithelium	UBERON:0004819	97.39	gold quality
cardiac atrium	UBERON:0002081	97.36	gold quality
right atrium auricular region	UBERON:0006631	97.36	gold quality
liver	UBERON:0002107	97.33	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESRRA, ESRRG, HNF4A, MYC, NR2F1, NR2F2, PPARA, TFAM

miRNA regulators (miRDB)

53 targeting ACADM, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-548AI	99.69	69.24	1494
HSA-MIR-548BA	99.69	69.14	1514
HSA-MIR-570-5P	99.69	69.24	1494
HSA-MIR-3177-5P	99.65	70.38	1174
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-516B-5P	99.56	66.33	1495

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• The results established that Drosophila miRNA dme-miR-34, is present in Drosophila embryos before initiation of zygotic transcription. (PMID:23470996)
• we show that the conserved miRNA miR-34 regulates innate immunity and ecdysone signaling in Drosophila (PMID:27893816)
• Study shows that ectopic overexpression of miR-34 impaired gamma axon pruning in differentiated mushroom body (MB) neurons, but did not inhibit axon degeneration in OSNs following axotomy. Its overexpression downregulated the expression of EcR-B1 in MB gamma neurons, and restoration of the EcR-B1 expression through over-expressing Babo and EcR-B1 rescued the miR-34-induced axon pruning defect in the MB neurons. (PMID:28008974)
• miR-34 modulates PRC2 activity to relieve silencing of genes promoting healthful aging. (PMID:30305625)
• Screen for novel regulators of synapse morphogenesis at the larval neuromuscular junction in Drosophila identified miR-34 as conserved synapse-regulatory miRNA and junctional receptor CNTNAP4/Neurexin-IV (Nrx-IV) and the membrane cytoskeletal effector Adducin/Hu-li tai shao (Hts) as proteins whose synaptic expression is restricted by miR-34. (PMID:32107390)
• Loss of miR-34 in Drosophila dysregulates protein translation and protein turnover in the aging brain. (PMID:35166006)
• Integrin restriction by miR-34 protects germline progenitors from cell death during aging. (PMID:38450871)
• The crystal structure of the carboxy-terminal region of the bacteriophage T4 proximal long tail fibre protein gp34 has been determined. (PMID:25005101)
• The structure reveals three repeats of a mixed alpha-beta fibrous domain in residues 744 to 877. A triple-helical neck connects to an extended triple beta-helix domain (amino acids 900-1127) punctuated by two beta-prism domains. (PMID:28665339)
• MCAD is induced by PGC-1 in an ERRalpha-dependent manner (PMID:12522104)
• Interference between PPARA and ERRalpha and RXRA complex heterodimer and the nuclear receptor site of MCAD (PMID:12914524)
• single arginine residue is essential for the binding of electron transferring flavoprotein to MCAD, but the single histidine residue, although involved, is not (PMID:14692513)
• first molecular identification of MCADD in an Arab patient and the first reported splice mutation in the MCAD gene that has been functionally characterized (PMID:15171999)
• Two novel rare mutations, R256T and K364R, have been investigated to assess how far the biochemical properties of the mutant proteins correlate with the clinical phenotype of medium chain acyl-CoA dehydrogenase deficiency. (PMID:16128823)
• analysis of MCAD deficiency (homozygous at c.985A>G (K329E)) complicated by acute liver failure in pregnancy [case report] (PMID:17186412)
• Measurement of MCAD activity in leukocytes or lymphocytes using phenylpropionyl-CoA as a substrate can be regarded as the gold standard to diagnose MCAD deficiency upon initial positive screening test results. (PMID:18188679)
• Six novel and seven previously reported medium chain acyl-CoA dehydrogenase mutations were detected in newborns with medium chain acyl-CoA dehydrogenase deficiency. (PMID:18241067)
• Ethnic-specific homozygous adenin/guanine substitution in an ACADM birth prevalence from a large-scale United Kingdom newborn screening study. (PMID:18927092)
• study indicates that c.449-452delCTGA represents a common mutation in Japanese patients with medium-chain acyl-CoA dehydrogenase deficiency (MCADD) (PMID:19064330)
• Protein misfolding of MCAD protein is the molecular basis in medium-chain acyl-CoA dehydrogenase deficiency. (PMID:19224950)
• In the medium-chain acyl-CoA dehydrogenase, the 985G mutant and 985A normal alleles had allelic frequencies of 0.0020 and 0.9980, respectively. (PMID:19551636)
• classification of genotypes with at least one variant of unknown significance in individuals who are carriers of, or affected with, MCAD deficiency of the following genotypes: c.985A>G/wildtype, c.199T>C/c.985A>G and c.985A>G/c.985A>G (PMID:20434380)
• Identify an ACADM founder mutation for MCADD in Saudi Arabian population. (PMID:20567907)
• The mutation in Medium-chain acyl-CoA dehydrogenase deficiency is the first report of the c.461T>G mutation in the acyl-CoA dehydrogenase gene. (PMID:21239873)
• physiological concentrations of flavin adenine dinucleotide resulted in a spectacular enhancement of the thermal stabilities of MCADH and prevented enzymatic activity loss (PMID:21968293)
• Subjects with variant ACADM genotypes and residual MCAD enzyme activities <10% should be considered to have the same risks as patients with classical ACADM genotypes (PMID:22630369)
• A novel variant in the Medium-Chain Acyl-CoA Dehydrogenase (MCAD) gene was identified in a Greek cohort of neonates with suspected MCAD deficiency. (PMID:22683754)
• The octanoyl-CoA oxidation rate, therefore, allows a risk assessment at birth and the identification of new ACADM genotypes associated with asymptomatic disease variants. (PMID:23028790)
• medium chain acyl-CoA dehydrogenase involve in the metabolism of phenylbutyrate. (PMID:23141465)
• This supports that c.1161A>G is a functional SNP, which leads to higher MCAD expression, perhaps due to improved splicing. This study is a proof of principle that synonymous SNPs are not neutral. (PMID:23810226)
• Segregation studies in the Gypsy families showed that 93/123 relatives were carriers of the acyl-coenzyme A dehydrogenase G985 allele, suggesting its high prevalence in this ethnic group. (PMID:23829193)
• mutations in the ACADM gene lower the temperature threshold at which medium-chain acyl-CoA dehydrogenase deficiency loss-of-function occurs. (PMID:24718418)
• our study demonstrates that not all mutations identified in children with abnormal NBS profiles suggestive of MCAD deficiency result in a total loss in MCAD activity and function (PMID:24966162)
• The c.600-18G > A variant activates a cryptic splice site, which competes with the natural splice site. (PMID:26223887)
• Study determined three mutations (p.R53C, p.R281S and p.G362E) in MCAD protein predisposing for MCAD deficiency which seems to be unique to Japanese population. (PMID:26947917)
• Exclusively breastfed neonates with MCAD are at risk for early metabolic decompensation. As breastfeeding rates increase, close management of feeding difficulties is essential for all neonates awaiting newborn screening results (PMID:27148938)
• 17 VUS (37%; 7 in ACADM, 9 in GALT, and 1 in PAH) were reclassified from uncertain (6 to benign or likely benign and 11 to pathogenic or likely pathogenic). We identified common types of missing information that would have helped make a definitive classification and categorized this information by ease and cost to obtain (PMID:27308838)
• Subjects with neonatal symptoms, or neonatal abnormal labs, or neonatal triggers were more likely to have at least one copy of the severe c.985A>G ACADM gene mutation (PMID:27477829)
• Our study has revealed the unique genetic backgrounds of MCAD deficiency among Japanese, based on the largest series of non-Caucasian cases. (PMID:27856190)
• LCHAD and MCAD are differentially expressed in maternal and fetal tissues during normal late pregnancy, which may represent a metabolic adaptation in response to physiological maternal dyslipidemia during late pregnancy. (PMID:27871288)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	acadm	ENSDARG00000038900
mus_musculus	Acadm	ENSMUSG00000062908
rattus_norvegicus	Acadm	ENSRNOG00000009845
caenorhabditis_elegans	acox-1.1	WBGENE00008564
caenorhabditis_elegans	acox-1.2	WBGENE00008565
caenorhabditis_elegans	acox-1.3	WBGENE00008566
caenorhabditis_elegans	acox-1.4	WBGENE00008567
caenorhabditis_elegans		WBGENE00015894
caenorhabditis_elegans	acdh-1	WBGENE00016943
caenorhabditis_elegans		WBGENE00019406
caenorhabditis_elegans		WBGENE00020366

Paralogs (14): ACADVL (ENSG00000072778), ACOX3 (ENSG00000087008), GCDH (ENSG00000105607), ACAD10 (ENSG00000111271), ACADL (ENSG00000115361), ACADS (ENSG00000122971), IVD (ENSG00000128928), ACAD8 (ENSG00000151498), ACOXL (ENSG00000153093), ACOX1 (ENSG00000161533), ACOX2 (ENSG00000168306), ACAD9 (ENSG00000177646), ACADSB (ENSG00000196177), ACAD11 (ENSG00000240303)

Protein

Protein identifiers

Medium-chain specific acyl-CoA dehydrogenase, mitochondrial — P11310 (reviewed: P11310)

Alternative names: Medium chain acyl-CoA dehydrogenase

All UniProt accessions (25): A0A0S2Z366, A0A7P0T8B6, A0A7P0T8G6, A0A7P0T8J9, A0A7P0T932, A0A7P0T9W7, A0A7P0TA39, A0A7P0TA63, A0A7P0TAB2, A0A7P0TAZ5, A0A7P0TB28, A0A7P0TB51, A0A7P0TB55, A0A7P0TBD1, A0A7P0TBF2, A0A7P0Z4Q0, E9PIX8, E9PJM9, E9PLN7, E9PQA8, E9PRX4, P11310, F6YB23, H0YDT5, Q5T4U5

UniProt curated annotations — full annotation on UniProt →

Function. Medium-chain specific acyl-CoA dehydrogenase is one of the acyl-CoA dehydrogenases that catalyze the first step of mitochondrial fatty acid beta-oxidation (FAO), breaking down fatty acids into acetyl-CoA and allowing the production of energy from fats. The first step of FAO consists in the proR-proR stereospecific alpha, beta-dehydrogenation of fatty acyl-CoA thioesters using the electron transfer flavoprotein (ETF) as their physiologic electron acceptor, resulting in the formation of trans-2-enoyl-CoA ((2E)-enoyl-CoA). ETF is the electron acceptor that transfers electrons to the main mitochondrial respiratory chain via ETF-ubiquinone oxidoreductase (ETF dehydrogenase). Among the different mitochondrial acyl-CoA dehydrogenases, medium-chain specific acyl-CoA dehydrogenase has preference for fatty acyl-CoAs with saturated 6 to 12 carbons long primary chains, making it but can also catalyze longer chains such as C14 and C16.

Subunit / interactions. Homotetramer (PubMed:8823176, Ref.24). Interacts with the heterodimeric electron transfer flavoprotein ETF.

Subcellular location. Mitochondrion matrix.

Tissue specificity. Expressed ubiquitously with highest levels in heart and muscle.

Post-translational modifications. Acetylated. Could occur at proximity of the cofactor-binding sites and reduce the catalytic activity. Could be deacetylated by SIRT3.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Lipid metabolism; mitochondrial fatty acid beta-oxidation.

Similarity. Belongs to the acyl-CoA dehydrogenase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P11310-1	1	yes
P11310-2	2

RefSeq proteins (5): NP_000007, NP_001120800, NP_001272971, NP_001272972, NP_001272973 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006089	Acyl-CoA_DH_CS	Conserved_site
IPR006091	AcylCoA_DH/ox_M	Domain
IPR009075	AcylCo_DH/oxidase_C	Domain
IPR009100	AcylCoA_DH/oxidase_NM_dom_sf	Homologous_superfamily
IPR013786	AcylCoA_DH/ox_N	Domain
IPR034180	MCAD	Family
IPR036250	AcylCo_DH-like_C	Homologous_superfamily
IPR037069	AcylCoA_DH/ox_N_sf	Homologous_superfamily
IPR046373	Acyl-CoA_Oxase/DH_mid-dom_sf	Homologous_superfamily
IPR050741

Pfam: PF00441, PF02770, PF02771

Enzyme classification (BRENDA):

• EC 1.3.8.7 — medium-chain acyl-CoA dehydrogenase (BRENDA: 16 organisms, 135 substrates, 55 inhibitors, 113 Km, 82 kcat entries)

Substrate kinetics (BRENDA)

40 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
OCTANOYL-COA	0.0008–1.47	27
HEXANOYL-COA	0.0014–0.0216	12
DECANOYL-COA	0.0007–0.05	11
BUTANOYL-COA	0.0084–0.45	9
DODECANOYL-COA	0.0025–0.05	6
HEXADECANOYL-COA	0.001–0.002	4
TETRADECANOYL-COA	0.0023–0.0057	4
ELECTRON TRANSFERRING FLAVOPROTEIN	0.0003–0.01	3
INDOLEPROPIONYL-COA	0.0005–0.01	3
BETA(2-FURYL)PROPIONYL-COA	0.001–0.007	2
ELECTRON TRANSFER FLAVOPROTEIN	0.0034–0.0045	2
FERROCENIUM HEXAFLUOROPHOSPHATE	0.0099–0.069	2
FURYLPROPIONYL-COA	0.014–0.0144	2
PALMITOYL-COA	0.0008–0.023	2
[4-(DIMETHYLAMINO)PHENYL]PROPIONYL-COA	0.0426–0.061	2

Catalyzed reactions (Rhea), 8 shown:

• a medium-chain 2,3-saturated fatty acyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = a medium-chain (2E)-enoyl-CoA + reduced [electron-transfer flavoprotein] (RHEA:14477)
• oxidized [electron-transfer flavoprotein] + hexadecanoyl-CoA + H(+) = (2E)-hexadecenoyl-CoA + reduced [electron-transfer flavoprotein] (RHEA:43448)
• pentanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-pentenoyl-CoA + reduced [electron-transfer flavoprotein] (RHEA:43456)
• hexanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-hexenoyl-CoA + reduced [electron-transfer flavoprotein] (RHEA:43464)
• dodecanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-dodecenoyl-CoA + reduced [electron-transfer flavoprotein] (RHEA:47296)
• tetradecanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-tetradecenoyl-CoA + reduced [electron-transfer flavoprotein] (RHEA:47316)
• decanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-decenoyl-CoA + reduced [electron-transfer flavoprotein] (RHEA:48176)
• octanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-octenoyl-CoA + reduced [electron-transfer flavoprotein] (RHEA:48180)

UniProt features (97 total): sequence variant 21, helix 19, modified residue 14, mutagenesis site 13, strand 13, binding site 10, turn 2, transit peptide 1, chain 1, active site 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
4P13	X-RAY DIFFRACTION	1.73
1EGD	X-RAY DIFFRACTION	2.4
1EGC	X-RAY DIFFRACTION	2.6
8SGP	ELECTRON MICROSCOPY	2.69
1EGE	X-RAY DIFFRACTION	2.75
2A1T	X-RAY DIFFRACTION	2.8
1T9G	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P11310-F1	93.15	0.91

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 401 (proton acceptor)

Ligand- & substrate-binding residues (10): 374–378; 401–405 (in other chain); 401; 158–167 (in other chain); 167; 191–193 (in other chain); 278; 281; 306–308; 316–317 (in other chain)

Post-translational modifications (14): 69, 69, 179, 212, 212, 217, 217, 259, 259, 271, 271, 279, 301, 351

Mutagenesis-validated functional residues (13):

Position	Phenotype
86	strongly reduced rate of electron transfer to etf.
98	strongly reduced rate of electron transfer to etf.
100	strongly reduced rate of electron transfer to etf.
108	strongly reduced rate of electron transfer to etf.
191	loss of electron transfer to etf.
191	reduces rate of electron transfer to etf about six-fold.
237	strongly reduced rate of electron transfer to etf.
280	narrower substrate specificity. changed substrate specificity towards longer acyl chains; when associated with g-401. lo
384	reduces rate of electron transfer to etf three-fold.
384	reduces rate of electron transfer to etf two-fold.
401	changed substrate specificity towards longer acyl chains; when associated with e-280.
401	loss of acyl-coa dehydrogenase activity.
401	loss of acyl-coa dehydrogenase activity; when associated with e-280.

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-1989781	PPARA activates gene expression
R-HSA-77288	mitochondrial fatty acid beta-oxidation of unsaturated fatty acids
R-HSA-77346	Beta oxidation of decanoyl-CoA to octanoyl-CoA-CoA
R-HSA-77348	Beta oxidation of octanoyl-CoA to hexanoyl-CoA
R-HSA-1430728	Metabolism
R-HSA-400206	Regulation of lipid metabolism by PPARalpha
R-HSA-556833	Metabolism of lipids
R-HSA-77286	mitochondrial fatty acid beta-oxidation of saturated fatty acids
R-HSA-77289	Mitochondrial Fatty Acid Beta-Oxidation
R-HSA-8978868	Fatty acid metabolism

MSigDB gene sets: 382 (showing top): GOBP_LIPID_MODIFICATION, MODULE_93, LIANG_HEMATOPOIESIS_STEM_CELL_NUMBER_SMALL_VS_HUGE_UP, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_FATTY_ACID_CATABOLIC_PROCESS, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_POLYSACCHARIDE_BIOSYNTHETIC_PROCESS, GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_RESPONSE_TO_COLD, PID_HNF3B_PATHWAY, MODULE_151, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_THE_CH_CH_GROUP_OF_DONORS, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, KEGG_VALINE_LEUCINE_AND_ISOLEUCINE_DEGRADATION

GO Biological Process (18): liver development (GO:0001889), glycogen biosynthetic process (GO:0005978), regulation of gluconeogenesis (GO:0006111), fatty acid beta-oxidation (GO:0006635), response to cold (GO:0009409), post-embryonic development (GO:0009791), carnitine metabolic process, CoA-linked (GO:0019254), fatty acid beta-oxidation using acyl-CoA dehydrogenase (GO:0033539), response to starvation (GO:0042594), carnitine biosynthetic process (GO:0045329), medium-chain fatty acid metabolic process (GO:0051791), medium-chain fatty acid catabolic process (GO:0051793), cardiac muscle cell differentiation (GO:0055007), obsolete organic acid metabolic process (GO:0006082), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631), heart development (GO:0007507), carnitine metabolic process (GO:0009437)

GO Molecular Function (6): acyl-CoA dehydrogenase activity (GO:0003995), identical protein binding (GO:0042802), flavin adenine dinucleotide binding (GO:0050660), medium-chain fatty acyl-CoA dehydrogenase activity (GO:0070991), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on the CH-CH group of donors (GO:0016627)

GO Cellular Component (9): nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), axon (GO:0030424), mitochondrial membrane (GO:0031966), perinuclear theca (GO:0033011), sperm principal piece (GO:0097228), sperm glycocalyx (GO:0120238)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Mitochondrial Fatty Acid Beta-Oxidation	2
mitochondrial fatty acid beta-oxidation of saturated fatty acids	2
Metabolism of lipids	2
Regulation of lipid metabolism by PPARalpha	1
Metabolism	1
Fatty acid metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
fatty acid catabolic process	2
response to stress	2
carnitine metabolic process	2
acyl-CoA dehydrogenase activity	2
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
mitochondrion	2
gland development	1
hepaticobiliary system development	1
glycogen metabolic process	1
glucan biosynthetic process	1
gluconeogenesis	1
regulation of glucose metabolic process	1
regulation of carbohydrate biosynthetic process	1
fatty acid ligase activity	1
fatty acid oxidation	1
response to temperature stimulus	1
multicellular organism development	1
multicellular organismal process	1
fatty acid beta-oxidation	1
response to nutrient levels	1
amino-acid betaine biosynthetic process	1
fatty acid metabolic process	1
medium-chain fatty acid metabolic process	1
cardiocyte differentiation	1
cardiac muscle tissue development	1
striated muscle cell differentiation	1
primary metabolic process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
animal organ development	1
circulatory system development	1
amino-acid betaine metabolic process	1
oxidoreductase activity, acting on the CH-CH group of donors, with a flavin as acceptor	1
protein binding	1
nucleotide binding	1
anion binding	1
catalytic activity	1
oxidoreductase activity	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

3018 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACADM	HADHA	P40939	871
ACADM	ACOX1	Q15067	803
ACADM	GRXCR1	A8MXD5	795
ACADM	SLC30A9	Q6PML9	790
ACADM	CPT2	P23786	783
ACADM	RPL9	P32969	763
ACADM	ACAA2	P42765	760
ACADM	CPT1A	P50416	756
ACADM	HADHB	P55084	747
ACADM	GABRB1	P18505	736
ACADM	CPT1B	Q92523	732
ACADM	ACOX3	O15254	724
ACADM	PPARA	Q07869	722
ACADM	ATP8A1	Q9Y2Q0	714
ACADM	HADH	Q16836	713

IntAct

63 interactions, top by confidence:

A	B	Type	Score
	PMPCB	psi-mi:“MI:0914”(association)	0.640
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
AKAP12	HSPA12A	psi-mi:“MI:0914”(association)	0.530
ACADM	ACADM	psi-mi:“MI:0407”(direct interaction)	0.440
ACADM	PNKD	psi-mi:“MI:0915”(physical association)	0.400
ACADM		psi-mi:“MI:0915”(physical association)	0.370
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
ANG	DDX39A	psi-mi:“MI:0914”(association)	0.350
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
P2RY6	ESYT2	psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
USP20		psi-mi:“MI:0914”(association)	0.350
USP50	IPO5	psi-mi:“MI:0914”(association)	0.350
TEX101	NDUFA4	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
ZDHHC5	HACD3	psi-mi:“MI:0914”(association)	0.350
DISC1	AGRN	psi-mi:“MI:0914”(association)	0.350
RYBP	PIPSL	psi-mi:“MI:0914”(association)	0.350
RYBP	FAM186A	psi-mi:“MI:0914”(association)	0.350
GABARAPL1		psi-mi:“MI:0914”(association)	0.350
ITM2B	ILVBL	psi-mi:“MI:0914”(association)	0.350
SMIM26	METTL15	psi-mi:“MI:0914”(association)	0.350
ASS1	TIMM44	psi-mi:“MI:0914”(association)	0.350
BLVRB	NDUFA3	psi-mi:“MI:0914”(association)	0.350
ESD	PIKFYVE	psi-mi:“MI:0914”(association)	0.350
HEATR3	TIMM44	psi-mi:“MI:0914”(association)	0.350

BioGRID (164): ACADM (Co-fractionation), ACADM (Co-fractionation), ACADM (Co-fractionation), ACADM (Co-fractionation), ACADM (Co-fractionation), ACADM (Co-fractionation), ACADM (Co-fractionation), ACADM (Co-fractionation), ACADM (Co-fractionation), ACADM (Co-fractionation), ACADM (Co-fractionation), ACADM (Co-fractionation), ACADM (Co-fractionation), ACADM (Co-fractionation), ACADM (Co-fractionation)

ESM2 similar proteins: A5A6I0, A8ALR4, A8WP91, A8XNF0, A9MQH5, B1XBG4, B4EY23, B7L4G2, B7UI85, B9U6P5, C3UVB0, C4ZPW5, F8GVD3, K4L7X3, P08503, P0A9U8, P0A9U9, P0A9V0, P11310, P12007, P15650, P26440, P28330, P41367, P45952, P45954, P51174, P70584, P79274, Q13PC1, Q22347, Q2LQN9, Q2LQP0, Q39QF4, Q39QF5, Q3SZB4, Q3SZI8, Q54RR5, Q5EAD4, Q5RBD5

Diamond homologs: A5A6I0, A8WP91, A8XNF0, B1WC61, B9U6P5, C3UVB0, D3JV03, F8GVD3, G3KIM8, H6LGM6, I6Y3V5, J7TF92, K4L7X3, O32176, O34421, O54143, P08503, P0A9U8, P0A9U9, P0A9V0, P11310, P12007, P15650, P15651, P16219, P26440, P28330, P41367, P45857, P45867, P45952, P45953, P45954, P46703, P48818, P49748, P50544, P51174, P52042, P63428

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
PPARG	“down-regulates activity”	ACADM	binding
ACADM	up-regulates	Fatty_acid_oxidation
ACADM	“down-regulates quantity”	decanoyl-CoA	“chemical modification”
ACADM	“down-regulates quantity”	FAD(3-)	“chemical modification”
ACADM	“up-regulates quantity”	FADH2(2-)	“chemical modification”
ACADM	“up-regulates quantity”	trans-dec-2-enoyl-CoA	“chemical modification”
ACADM	“down-regulates quantity”	octanoyl-CoA	“chemical modification”
ACADM	“up-regulates quantity”	trans-oct-2-enoyl-CoA(4-)	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

1114 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	127
Likely pathogenic	161
Uncertain significance	267
Likely benign	301
Benign	50

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1068571	NM_000016.6(ACADM):c.1045C>G (p.Arg349Gly)	Pathogenic
1068759	NM_000016.6(ACADM):c.203del (p.Asp68fs)	Pathogenic
1070356	NM_000016.6(ACADM):c.799_803del (p.Gly267fs)	Pathogenic
1070530	NM_000016.6(ACADM):c.377del (p.Asn126fs)	Pathogenic
1073714	NM_000016.6(ACADM):c.243_250del (p.Glu83fs)	Pathogenic
1356922	NM_000016.6(ACADM):c.1067T>C (p.Ile356Thr)	Pathogenic
1368883	NM_000016.6(ACADM):c.801del (p.Ala268fs)	Pathogenic
1369032	NM_000016.6(ACADM):c.30+2T>G	Pathogenic
1371575	NM_000016.6(ACADM):c.652del (p.Ala218fs)	Pathogenic
1380272	NM_000016.6(ACADM):c.468+2T>C	Pathogenic
1396357	NC_000001.10:g.(?76211473)(76228458_?)del	Pathogenic
1428164	NM_000016.6(ACADM):c.1A>T (p.Met1Leu)	Pathogenic
1431508	NM_000016.6(ACADM):c.1175G>A (p.Arg392Lys)	Pathogenic
1438490	NM_000016.6(ACADM):c.727C>T (p.Arg243Ter)	Pathogenic
1451991	NM_000016.6(ACADM):c.168del (p.Arg57fs)	Pathogenic
1453591	NM_000016.6(ACADM):c.741_742dup (p.Arg248fs)	Pathogenic
1453773	NM_000016.6(ACADM):c.1011C>A (p.Tyr337Ter)	Pathogenic
1454518	NM_000016.6(ACADM):c.342T>A (p.Tyr114Ter)	Pathogenic
1454534	NM_000016.6(ACADM):c.518del (p.Lys173fs)	Pathogenic
1454734	NM_000016.6(ACADM):c.1010dup (p.Tyr337Ter)	Pathogenic
1456859	NC_000001.10:g.(?76194064)(76216241_?)del	Pathogenic
1458793	NM_000016.6(ACADM):c.1022_1029del (p.Ala341fs)	Pathogenic
1459341	NC_000001.10:g.(?76190473)(76200576_?)del	Pathogenic
147765	GRCh38/hg38 1p32.1-22.3(chr1:58819605-86098611)x1	Pathogenic
1510903	NM_000016.6(ACADM):c.338C>A (p.Ala113Asp)	Pathogenic
155062	GRCh38/hg38 1p31.3-31.1(chr1:66865125-77123381)x1	Pathogenic
1683220	NC_000001.10:g.(76216232_76226806)(76229365?)del	Pathogenic
188934	NM_000016.6(ACADM):c.244dup (p.Trp82fs)	Pathogenic
189016	NM_000016.6(ACADM):c.1045C>T (p.Arg349Ter)	Pathogenic
189019	NM_000016.6(ACADM):c.977T>C (p.Met326Thr)	Pathogenic

SpliceAI

2322 predictions. Top by Δscore:

Variant	Effect	Δscore
1:75728471:GAT:G	donor_gain	1.0000
1:75732641:TA:T	acceptor_loss	1.0000
1:75732642:A:AC	acceptor_loss	1.0000
1:75732642:A:AG	acceptor_gain	1.0000
1:75732643:G:GG	acceptor_gain	1.0000
1:75732643:G:GT	acceptor_loss	1.0000
1:75732643:GA:G	acceptor_gain	1.0000
1:75732643:GAGTT:G	acceptor_gain	1.0000
1:75732737:GTGAA:G	donor_gain	1.0000
1:75732739:G:GT	donor_gain	1.0000
1:75732739:GAA:G	donor_gain	1.0000
1:75732742:G:GG	donor_gain	1.0000
1:75732851:A:AG	acceptor_gain	1.0000
1:75732852:G:GG	acceptor_gain	1.0000
1:75732852:GT:G	acceptor_gain	1.0000
1:75734868:GTGT:G	donor_gain	1.0000
1:75734870:GT:G	donor_gain	1.0000
1:75734872:G:GG	donor_gain	1.0000
1:75739969:A:AG	acceptor_gain	1.0000
1:75739970:T:G	acceptor_gain	1.0000
1:75739971:A:AG	acceptor_gain	1.0000
1:75739972:T:G	acceptor_gain	1.0000
1:75739973:A:AG	acceptor_gain	1.0000
1:75739974:T:G	acceptor_gain	1.0000
1:75739977:A:AG	acceptor_gain	1.0000
1:75739977:AAG:A	acceptor_gain	1.0000
1:75739978:A:AG	acceptor_gain	1.0000
1:75739978:AG:A	acceptor_gain	1.0000
1:75739979:G:GG	acceptor_gain	1.0000
1:75739979:GG:G	acceptor_gain	1.0000

AlphaMissense

2750 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:75739988:T:G	C159W	0.999
1:75739993:C:T	T161I	0.999
1:75740082:T:A	W191R	0.999
1:75740082:T:C	W191R	0.999
1:75762701:G:C	G402R	0.999
1:75740010:T:C	S167P	0.998
1:75740071:G:T	G187V	0.998
1:75740078:G:C	K189N	0.998
1:75740078:G:T	K189N	0.998
1:75740086:T:A	I192K	0.998
1:75745871:T:C	F222S	0.998
1:75749431:G:C	G241R	0.998
1:75749552:G:C	R281T	0.998
1:75750496:G:C	A299P	0.998
1:75761250:G:C	K358N	0.998
1:75761250:G:T	K358N	0.998
1:75761315:G:A	G380E	0.998
1:75761351:G:T	R392M	0.998
1:75762701:G:T	G402C	0.998
1:75739986:T:C	C159R	0.997
1:75739987:G:A	C159Y	0.997
1:75739993:C:A	T161K	0.997
1:75739993:C:G	T161R	0.997
1:75739996:A:T	E162V	0.997
1:75740011:C:A	S167Y	0.997
1:75740076:A:C	K189Q	0.997
1:75740084:G:C	W191C	0.997
1:75740084:G:T	W191C	0.997
1:75740095:G:A	G195E	0.997
1:75749432:G:A	G241D	0.997

dbSNP variants (sampled 300 via entrez): RS1000069944 (1:75727277 A>G), RS1000092309 (1:75744525 C>T), RS1000223358 (1:75736120 T>C,G), RS1000237605 (1:75730020 A>C,G), RS1000237620 (1:75747980 A>T), RS1000271484 (1:75751157 C>T), RS1000309787 (1:75747552 G>C), RS1000351828 (1:75730370 A>G,T), RS1000467248 (1:75724260 C>A,T), RS1000531516 (1:75742079 G>A), RS1000590032 (1:75746127 G>T), RS1000637749 (1:75741380 T>C), RS1000655999 (1:75761889 T>A), RS1000833910 (1:75752182 A>G), RS1000874642 (1:75749967 T>C)

Disease associations

OMIM: gene MIM:607008 | disease phenotypes: MIM:201450, MIM:615219, MIM:201470

GenCC curated gene-disease

Disease	Classification	Inheritance
medium chain acyl-CoA dehydrogenase deficiency	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
medium chain acyl-CoA dehydrogenase deficiency	Definitive	AR

Mondo (3): medium chain acyl-CoA dehydrogenase deficiency (MONDO:0008721), hydrocephalus, nonsyndromic, autosomal recessive 2 (MONDO:0014085), short chain acyl-CoA dehydrogenase deficiency (MONDO:0008722)

Orphanet (3): Medium chain acyl-CoA dehydrogenase deficiency (Orphanet:42), Congenital hydrocephalus (Orphanet:2185), Short chain acyl-CoA dehydrogenase deficiency (Orphanet:26792)

HPO phenotypes

48 total (30 of 48 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000256	Macrocephaly
HP:0000750	Delayed speech and language development
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001254	Lethargy
HP:0001259	Coma
HP:0001263	Global developmental delay
HP:0001290	Generalized hypotonia
HP:0001315	Reduced tendon reflexes
HP:0001397	Hepatic steatosis
HP:0001410	Decreased liver function
HP:0001640	Cardiomegaly
HP:0001942	Metabolic acidosis
HP:0001943	Hypoglycemia
HP:0001946	Ketosis
HP:0001987	Hyperammonemia
HP:0002013	Vomiting
HP:0002014	Diarrhea
HP:0002069	Bilateral tonic-clonic seizure
HP:0002181	Cerebral edema
HP:0002240	Hepatomegaly
HP:0002373	Febrile seizure (within the age range of 3 months to 6 years)
HP:0002875	Exertional dyspnea
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0003108	Hyperglycinuria
HP:0003198	Myopathy
HP:0003202	Skeletal muscle atrophy
HP:0003215	Dicarboxylic aciduria

GWAS associations

28 associations (top):

Study	Trait	p-value
GCST000550_1	Metabolite levels	1.000000e-63
GCST001217_15	Metabolic traits	2.000000e-71
GCST003518_71	Daytime sleep phenotypes	8.000000e-07
GCST005648_33	Serum metabolite concentrations in chronic kidney disease	1.000000e-12
GCST005650_211	Serum metabolite ratios in chronic kidney disease	2.000000e-18
GCST005650_212	Serum metabolite ratios in chronic kidney disease	4.000000e-30
GCST006249_1	Serum metabolite levels	2.000000e-21
GCST006249_70	Serum metabolite levels	2.000000e-27
GCST006249_89	Serum metabolite levels	5.000000e-43
GCST006249_94	Serum metabolite levels	3.000000e-36
GCST007638_49	Glycine levels	8.000000e-19
GCST007836_1	Glycine levels	1.000000e-11
GCST007838_1	Glycine levels	1.000000e-09
GCST009733_17	Urinary metabolite levels in chronic kidney disease	3.000000e-14
GCST009733_19	Urinary metabolite levels in chronic kidney disease	2.000000e-20
GCST009733_190	Urinary metabolite levels in chronic kidney disease	2.000000e-20
GCST009733_21	Urinary metabolite levels in chronic kidney disease	5.000000e-23
GCST009733_225	Urinary metabolite levels in chronic kidney disease	5.000000e-18
GCST009733_31	Urinary metabolite levels in chronic kidney disease	3.000000e-24
GCST009733_33	Urinary metabolite levels in chronic kidney disease	6.000000e-25
GCST009733_89	Urinary metabolite levels in chronic kidney disease	2.000000e-18
GCST009735_24	Urinary metabolite modules (eigenmetabolites) in chronic kidney disease	8.000000e-13
GCST009735_25	Urinary metabolite modules (eigenmetabolites) in chronic kidney disease	8.000000e-26
GCST012020_229	Serum metabolite levels	7.000000e-47
GCST012020_230	Serum metabolite levels	5.000000e-73
GCST012020_33	Serum metabolite levels	2.000000e-23
GCST012020_556	Serum metabolite levels	2.000000e-15
GCST012021_29	Serum metabolite levels	2.000000e-15

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004725	metabolite measurement
EFO:0007828	daytime rest measurement
EFO:0009767	glycine measurement
EFO:0005116	urinary metabolite measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C536038	Medium chain acyl CoA dehydrogenase deficiency (supp.)
C537596	Short chain Acyl CoA dehydrogenase deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295713 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

81 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
perfluorooctanoic acid	increases expression, affects cotreatment	5
Valproic Acid	increases response to substance, decreases expression, increases expression, increases methylation	4
bisphenol A	decreases expression, increases expression	3
Resveratrol	affects cotreatment, increases expression	2
Benzo(a)pyrene	affects methylation, increases expression	2
Diethylhexyl Phthalate	affects response to substance, increases expression	2
Fenofibrate	increases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Cyclosporine	decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
apocarotenal	increases expression	1
lasiocarpine	decreases expression	1
triphenyl phosphate	affects expression	1
fenofibric acid	increases expression, affects binding	1
pirinixic acid	increases expression, affects binding, increases activity	1
4,4’-bisphenol F	increases expression	1
dioctyl adipate	affects response to substance, increases expression	1
beta-lapachone	decreases expression, increases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
sodium arsenite	decreases expression	1
nickel chloride	decreases expression	1
beta-hexachlorocyclohexane	decreases expression	1
manganese chloride	increases abundance, increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
di-n-hexyl phthalate	decreases expression	1
acipimox	increases expression	1
AICA ribonucleotide	increases expression	1
ciglitazone	affects binding, increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118582	Binding	Binding affinity to ACADM in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

17 cell lines: 10 finite cell line, 7 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_4F50	GM04488	Finite cell line	Female
CVCL_4F51	GM05872	Finite cell line	Female
CVCL_4F53	GM06125	Finite cell line	Female
CVCL_4F55	GM07523	Transformed cell line	Female
CVCL_4F56	GM07842	Finite cell line	Female
CVCL_4F57	GM07844	Finite cell line	Male
CVCL_4F59	GM08684	Finite cell line	Female
CVCL_4F60	GM08768	Finite cell line	Female
CVCL_4F62	GM11319	Transformed cell line	Female
CVCL_4F63	GM11320	Transformed cell line	Female

Clinical trials (associated diseases)

21 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT06759272	PHASE4	NOT_YET_RECRUITING	Impact of CYP2C19 Genotype-guided Approach in Antiplatelet Therapy on Platelet Reactivity Index Among Coronary Artery Disease (CAD) Patients
NCT06067802	PHASE2	SUSPENDED	Study of Triheptanoin for the Prevention of Hypoglycemia in Patients With Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCADD)
NCT06069375	PHASE2	SUSPENDED	Study of Sodium Phenylbutyrate (ACER-001) for the Treatment of Patients With Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCADD)
NCT06773026	PHASE2	RECRUITING	Study of Sodium Phenylbutyrate (ACER-001) for the Treatment of Pediatric and Adults Patients With Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCADD)
NCT07097311	PHASE2	RECRUITING	Study to Evaluate the Use of Triheptanoin in Patients With Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCADD)
NCT01881984	PHASE1	COMPLETED	Use of Ravicti™ in Patients With MCAD Deficiency With the 985A>G (K304E) Mutation
NCT02517307	Not specified	COMPLETED	Fatty Acid Oxidation Defects and Insulin Sensitivity
NCT02635269	Not specified	UNKNOWN	Fat and Sugar Metabolism During Exercise in Patients With Metabolic Myopathy
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT03761693	Not specified	UNKNOWN	Fasting Tolerance in MCADD-infants
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening
NCT05910151	Not specified	UNKNOWN	Selective Screening of Children for Hereditary Metabolic Diseases by Tandem Mass Spectrometry in Kazakhstan
NCT06623032	Not specified	RECRUITING	Metabolic Effects of Medium-Chain Fatty Acids in Patients With Medium-Chain Acyl-CoA Dehydrogenase Deficiency and Healthy Individuals
NCT06796530	Not specified	COMPLETED	High Intensity Exercise in Children With MCADD
NCT05122455	PHASE2/PHASE3	COMPLETED	Effects of Edoxaban on Platelet Aggregation
NCT01427179	Not specified	RECRUITING	Genetic Investigations in Spontaneous Coronary Artery Dissection (SCAD)
NCT01429727	Not specified	RECRUITING	The Virtual Multicenter Spontaneous Coronary Artery Dissection (SCAD) Registry
NCT03941184	Not specified	COMPLETED	Spontaneous Coronary Artery Dissection (SCAD) and Autoimmunity
NCT04906356	Not specified	RECRUITING	Canadian SCAD Study
NCT04936438	Not specified	ACTIVE_NOT_RECRUITING	Clinical Cohort Study - INTERCATH
NCT07317323	Not specified	RECRUITING	Norwegian Spontaneous Coronary Artery Dissection Study