HADHA

Summary

HADHA (hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha, HGNC:4801) is a protein-coding gene on chromosome 2p23.3, encoding Trifunctional enzyme subunit alpha, mitochondrial (P40939). Mitochondrial trifunctional enzyme catalyzes the last three of the four reactions of the mitochondrial beta-oxidation pathway.

This gene encodes the alpha subunit of the mitochondrial trifunctional protein, which catalyzes the last three steps of mitochondrial beta-oxidation of long chain fatty acids. The mitochondrial membrane-bound heterocomplex is composed of four alpha and four beta subunits, with the alpha subunit catalyzing the 3-hydroxyacyl-CoA dehydrogenase and enoyl-CoA hydratase activities. Mutations in this gene result in trifunctional protein deficiency or LCHAD deficiency. The genes of the alpha and beta subunits of the mitochondrial trifunctional protein are located adjacent to each other in the human genome in a head-to-head orientation.

Source: NCBI Gene 3030 — RefSeq curated summary.

At a glance

• Gene–disease (curated): long chain 3-hydroxyacyl-CoA dehydrogenase deficiency (Definitive, ClinGen) — +2 more curated relationships
• Clinical variants (ClinVar): 804 total — 59 pathogenic, 69 likely-pathogenic
• Phenotypes (HPO): 87
• Druggable target: yes
• MANE Select transcript: NM_000182

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4801
Approved symbol	HADHA
Name	hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha
Location	2p23.3
Locus type	gene with protein product
Status	Approved
Aliases	GBP, LCEH, LCHAD, MTPA
Ensembl gene	ENSG00000084754
Ensembl biotype	protein_coding
OMIM	600890
Entrez	3030

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 27 protein_coding, 6 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000380649, ENST00000461025, ENST00000471743, ENST00000492433, ENST00000643057, ENST00000643063, ENST00000643233, ENST00000644428, ENST00000645274, ENST00000646031, ENST00000646483, ENST00000859324, ENST00000859325, ENST00000859326, ENST00000859327, ENST00000859328, ENST00000859329, ENST00000859330, ENST00000859331, ENST00000859332, ENST00000859333, ENST00000925541, ENST00000942141, ENST00000942142, ENST00000942143, ENST00000942144, ENST00000942145, ENST00000942146, ENST00000942147, ENST00000942148, ENST00000942149, ENST00000942150, ENST00000942151, ENST00000942152, ENST00000942153

RefSeq mRNA: 1 — MANE Select: NM_000182 NM_000182

CCDS: CCDS1721

Canonical transcript exons

ENST00000380649 — 20 exons

Exon	Start	End
ENSE00000542494	26215053	26215175
ENSE00000542497	26209780	26209889
ENSE00000542500	26197691	26197777
ENSE00000542501	26195092	26195232
ENSE00000542504	26192310	26192424
ENSE00000730279	26191483	26191628
ENSE00000730285	26193577	26193772
ENSE00000730445	26194570	26194638
ENSE00000730454	26201149	26201320
ENSE00000730458	26204062	26204196
ENSE00000730463	26212570	26212626
ENSE00000730653	26230192	26230294
ENSE00000932327	26232160	26232279
ENSE00000932329	26236855	26236988
ENSE00001485736	26190635	26191395
ENSE00001485795	26244530	26244632
ENSE00003580098	26239102	26239143
ENSE00003618655	26234217	26234355
ENSE00003636800	26214443	26214561
ENSE00003660831	26238934	26239004

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.24.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 137.6736 / max 1440.3867, expressed in 1826 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
27416	131.4266	1826
27417	4.6871	1693
27418	1.5599	565

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	99.24	gold quality
gastrocnemius	UBERON:0001388	99.11	gold quality
muscle of leg	UBERON:0001383	99.00	gold quality
heart left ventricle	UBERON:0002084	98.91	gold quality
cardiac ventricle	UBERON:0002082	98.88	gold quality
apex of heart	UBERON:0002098	98.88	gold quality
duodenum	UBERON:0002114	98.78	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.71	gold quality
muscle organ	UBERON:0001630	98.68	gold quality
jejunum	UBERON:0002115	98.63	gold quality
right atrium auricular region	UBERON:0006631	98.60	gold quality
mucosa of transverse colon	UBERON:0004991	98.55	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.54	gold quality
heart	UBERON:0000948	98.49	gold quality
cardiac atrium	UBERON:0002081	98.49	gold quality
adrenal tissue	UBERON:0018303	98.43	gold quality
rectum	UBERON:0001052	98.34	gold quality
diaphragm	UBERON:0001103	98.33	gold quality
monocyte	CL:0000576	98.26	gold quality
deltoid	UBERON:0001476	98.22	gold quality
right adrenal gland	UBERON:0001233	98.19	gold quality
heart right ventricle	UBERON:0002080	98.17	gold quality
skeletal muscle tissue	UBERON:0001134	98.16	gold quality
islet of Langerhans	UBERON:0000006	98.15	gold quality
left adrenal gland	UBERON:0001234	98.15	gold quality
right adrenal gland cortex	UBERON:0035827	98.15	gold quality
mononuclear cell	CL:0000842	98.12	gold quality
leukocyte	CL:0000738	98.08	gold quality
left adrenal gland cortex	UBERON:0035825	98.06	gold quality
mucosa of stomach	UBERON:0001199	98.05	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ENAD-17	no	1959.89
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

42 targeting HADHA, 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-6867-5P	100.00	82.21	3464
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-6126	99.62	68.09	996
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-6740-3P	99.48	68.49	1392

Literature-anchored findings (GeneRIF, showing 40)

• The G1528C (E474Q) mutation in the alpha-subunit of the mitochondrial trifunctional protein was not found in 10 women with acute fatty liver of pregnancy. (PMID:11978893)
• Plasma concentration varied more than erythrocyte levels. Postprandial period and fasting. (PMID:12971430)
• Both alpha- and beta-subunit mutations result in TFP complex instability, demonstrating that the mechanism of disease is the same in alpha- or beta-mutation-derived disease and explaining the biochemical and clinical similarities. (PMID:14630990)
• The retinal pigment epithelium rather than the choriocapillaris could be the critical affected cell layer in LCHAD retinopathy (PMID:15347768)
• DNA analysis of patients 1 and 2 revealed homozygosity for a c.1689+2T>G mutation of the HADHA gene, resulting in the skipping of exon 16 with an in-frame 69-bp deletion. (PMID:17143551)
• Neither maternal nor fetal heterozygosity for the E474Q mutation is a relevant factor of HELLP syndrome. (PMID:17313315)
• There might be diverse etiological factors in China contributing to AFLP other than the frequently reported mutation in the LCHAD. (PMID:18031367)
• The second of 220 SIDs cases was a compound heterozygous for the prevalent MTP G1528C mutation and a novel 1 bp deletion in exon 18 of the MTPalpha-subunit gene. (PMID:18045290)
• Severe cardiac mitochondrial proliferation and TFP deficiency was observed in intrauterine cardiomyopathy. (PMID:18485779)
• identify MLCL AT-1 as a human mitochondrial monolysocardiolipin acyltransferase involved in the remodeling of cardiolipin (PMID:19737925)
• Report probable Kashubian origin of the prevalent HADHA c.1528G>C mutation responsible for long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency in Poland. (PMID:20814823)
• Recombinant mitochondrial trifunctional protein displayed 2-enoyl-CoA hydratase, l-3-hydroxyacyl-CoA dehydrogenase, and 3-ketoacyl-CoA thiolase activities. (PMID:20825197)
• Results emphasize the value of cDNA analysis in the characterization of HADHA and HADHB mutations and further strengthen the model of haploinsufficiency as a major pathomechanism in MTP defects. (PMID:21549624)
• Both children were homozygous for the common mutation c.1528G>C and the parents were heterozygous for this same mutation. (PMID:22325456)
• High HADHA protein expression is associated with response to platinum-based chemotherapy for lung cancer. (PMID:22471497)
• TP-alpha, collagen alpha-1(VI) chain and S100A9 are potential biomarkers of esophageal squamous cell carcinoma, and may play an important role in tumorigenesis and development of ESCC. (PMID:22583932)
• these findings lend support to the hypothesis that mutations in the HADHA gene may be directly associated with and potentially causative of Maternal floor infarction/massive perivillous fibrin deposition (PMID:22746996)
• mitochondrial alphaTFP exhibits both in vitro and in vivo MLCL AT activity linking an enzyme of mitochondrial beta-oxidation to Cardiolipin remodeling. (PMID:23152787)
• Free fatty acids might affect the expression of mitochondrial beta-oxidation enzyme of LCHAD in trophoblast cells. (PMID:23253803)
• revealed a novel G/A allelic change in the intronic region [chromosomal position 26417674; 20 bp adjacent to an already published SNP (rs151243950)] for one among the three acute fatty liver of pregnancy patients (PMID:24105666)
• Crystal structures of human mitochondrial 3-ketoacyl-CoA thiolase (hT1) in the apo form and in complex with CoA have been determined at 2.0 A resolution. The structures confirm the tetrameric quaternary structure of this degradative thiolase. (PMID:25478839)
• Mitochondrial Trifunctional-Protein depletion during hepatitis c virus infection rendered cells less responsive to alpha interferon treatment by impairing IFN-stimulated gene expression. (PMID:25673715)
• nonstructural protein 5 (NS5) interacted with hydroxyacyl-CoA dehydrogenase alpha and beta subunits, two components of the mitochondrial trifunctional protein (MTP) involved in LCFA beta-oxidation (PMID:25816318)
• Exposure to bezafibrate (400 muM for 48 h) increased the abundance of HADHA and HADHB mRNAs. (PMID:26109258)
• findings suggest an auxiliary role for HADHA in miRNA biogenesis and help in better understanding of molecular mechanisms underlying RNAi pathway (PMID:26367179)
• Low HADHA expression is associated with clear cell renal cell carcinoma. (PMID:26715271)
• study indicate described high frequency of c.1528G>C variant of HADHA gene in Kashubian population, suggesting the founder effect. For the first time we have found high frequency of rs71441018 in the South Poland Silesian population (PMID:29095929)
• The authors provide novel insights into the cellular energy household of cells from HADHA/ACADVL patients and demonstrate for the first time a connection between fatty acid metabolism, mitochondrial morphology and reactive oxygen species in patients with these rare genetic disorders. (PMID:29459657)
• HADHA overexpression disrupted lipid metabolism. (PMID:31472118)
• Fatty acid beta oxidation enzyme HADHA is a novel potential therapeutic target in malignant lymphoma. (PMID:31527828)
• Cardioprotective GLP-1 metabolite prevents ischemic cardiac injury by inhibiting mitochondrial trifunctional protein-alpha. (PMID:31985487)
• MiR-612 regulates invadopodia of hepatocellular carcinoma by HADHA-mediated lipid reprogramming. (PMID:32033570)
• Deep geno- and phenotyping in two consanguineous families with CMT2 reveals HADHA as an unusual disease-causing gene and an intronic variant in GDAP1 as an unusual mutation. (PMID:32897397)
• Targeting the mitochondrial trifunctional protein restrains tumor growth in oxidative lung carcinomas. (PMID:33393495)
• Human Peroxisomal 3-Ketoacyl-CoA Thiolase: Tissue Expression and Metabolic Regulation : Human Peroxisomal Thiolase. (PMID:33417214)
• Roles of hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha, a lipid metabolism enzyme, in Wilms tumor patients. (PMID:34850779)
• Analysis of a family with mitochondrial trifunctional protein deficiency caused by HADHA gene mutations. (PMID:34878152)
• [HADHA Inhibits the Migration and Invasion of HTR-8/SVneo Cells by Regulating PI3K/AKT Signaling Pathway]. (PMID:36224682)
• An Autopsy Analysis of a Patient With Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency Caused by Compound Heterozygous HADHA Gene Mutations. (PMID:37549033)
• Zfp335 establishes eTreg lineage and neonatal immune tolerance by targeting Hadha-mediated fatty acid oxidation. (PMID:37843279)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	hadhaa	ENSDARG00000057128
danio_rerio	hadhab	ENSDARG00000060594
mus_musculus	Hadha	ENSMUSG00000025745
rattus_norvegicus	Hadha	ENSRNOG00000024629
drosophila_melanogaster	Mtpalpha	FBGN0028479
caenorhabditis_elegans		WBGENE00001150
caenorhabditis_elegans	ech-1.2	WBGENE00020347

Paralogs (3): EHHADH (ENSG00000113790), HADH (ENSG00000138796), CRYL1 (ENSG00000165475)

Protein

Protein identifiers

Trifunctional enzyme subunit alpha, mitochondrial — P40939 (reviewed: P40939)

Alternative names: 78 kDa gastrin-binding protein, Monolysocardiolipin acyltransferase, TP-alpha

All UniProt accessions (8): P40939, A0A2R8Y4E0, A0A2R8Y4F5, A0A2R8Y688, A0A2R8YDM1, A0A2R8YG21, E9KL44, H0YFD6

UniProt curated annotations — full annotation on UniProt →

Function. Mitochondrial trifunctional enzyme catalyzes the last three of the four reactions of the mitochondrial beta-oxidation pathway. The mitochondrial beta-oxidation pathway is the major energy-producing process in tissues and is performed through four consecutive reactions breaking down fatty acids into acetyl-CoA. Among the enzymes involved in this pathway, the trifunctional enzyme exhibits specificity for long-chain fatty acids. Mitochondrial trifunctional enzyme is a heterotetrameric complex composed of two proteins, the trifunctional enzyme subunit alpha/HADHA described here carries the 2,3-enoyl-CoA hydratase and the 3-hydroxyacyl-CoA dehydrogenase activities while the trifunctional enzyme subunit beta/HADHB bears the 3-ketoacyl-CoA thiolase activity. Independently of subunit beta, HADHA also exhibits a cardiolipin acyltransferase activity that participates in cardiolipin remodeling; cardiolipin is a major mitochondrial membrane phospholipid. HADHA may act downstream of Tafazzin/TAZ, that remodels monolysocardiolipin (MLCL) to a cardiolipin intermediate, and then HADHA may continue to remodel this species into mature tetralinoleoyl-cardiolipin. Has also been proposed to act directly on MLCL; capable of acylating MLCL using different acyl-CoA substrates, with highest activity for oleoyl-CoA.

Subunit / interactions. Heterotetramer of 2 alpha/HADHA and 2 beta/HADHB subunits; forms the mitochondrial trifunctional enzyme. Also purified as higher order heterooligomers including a 4 alpha/HADHA and 4 beta/HADHB heterooligomer which physiological significance remains unclear. The mitochondrial trifunctional enzyme interacts with MTLN.

Subcellular location. Mitochondrion. Mitochondrion inner membrane.

Disease relevance. Mitochondrial trifunctional protein deficiency 1 (MTPD1) [MIM:609015] An autosomal recessive metabolic disorder of long-chain fatty acid oxidation, biochemically characterized by loss of all enzyme activities of the mitochondrial trifunctional protein complex. The disease phenotype ranges from a fatal form characterized by early-onset cardiomyopathy, cardiac failure and early death to less severe, late-onset forms with myopathy, recurrent rhabdomyolysis, and sensorimotor axonal neuropathy as key features. The disease is caused by variants affecting the gene represented in this entry. Long-chain 3-hydroxyl-CoA dehydrogenase deficiency (LCHAD deficiency) [MIM:609016] The clinical features are very similar to TFP deficiency. Biochemically, LCHAD deficiency is characterized by reduced long-chain 3-hydroxyl-CoA dehydrogenase activity, while the other enzyme activities of the TFP complex are normal or only slightly reduced. The disease is caused by variants affecting the gene represented in this entry. Maternal acute fatty liver of pregnancy (AFLP) [MIM:609016] Severe maternal illness occurring during pregnancies with affected fetuses. This disease is associated with LCHAD deficiency and characterized by sudden unexplained infant death or hypoglycemia and abnormal liver enzymes (Reye-like syndrome). The disease is caused by variants affecting the gene represented in this entry.

Induction. Up-regulated by thyroid hormone (at protein level).

Pathway. Lipid metabolism; fatty acid beta-oxidation.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. In the N-terminal section; belongs to the enoyl-CoA hydratase/isomerase family. In the central section; belongs to the 3-hydroxyacyl-CoA dehydrogenase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P40939-1	1	yes
P40939-2	2

RefSeq proteins (1): NP_000173* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001753	Enoyl-CoA_hydra/iso	Domain
IPR006108	3HC_DH_C	Domain
IPR006176	3-OHacyl-CoA_DH_NAD-bd	Domain
IPR006180	3-OHacyl-CoA_DH_CS	Conserved_site
IPR008927	6-PGluconate_DH-like_C_sf	Homologous_superfamily
IPR012803	Fa_ox_alpha_mit	Family
IPR018376	Enoyl-CoA_hyd/isom_CS	Conserved_site
IPR029045	ClpP/crotonase-like_dom_sf	Homologous_superfamily
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily
IPR050136	FA_oxidation_alpha_subunit	Family

Pfam: PF00378, PF00725, PF02737

Enzyme classification (BRENDA):

• EC 1.1.1.211 — long-chain-3-hydroxyacyl-CoA dehydrogenase (BRENDA: 5 organisms, 11 substrates, 1 inhibitors, 2 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

2 substrates with measured Km, best-characterized 2. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
NAD+	0.06	1
NADH	0.05	1

Catalyzed reactions (Rhea), 12 shown:

• a (3S)-3-hydroxyacyl-CoA = a (2E)-enoyl-CoA + H2O (RHEA:16105)
• a 4-saturated-(3S)-3-hydroxyacyl-CoA = a (3E)-enoyl-CoA + H2O (RHEA:20724)
• (3S)-3-hydroxydodecanoyl-CoA = (2E)-dodecenoyl-CoA + H2O (RHEA:31075)
• (3S)-hydroxyhexadecanoyl-CoA + NAD(+) = 3-oxohexadecanoyl-CoA + NADH + H(+) (RHEA:31159)
• (3S)-hydroxyhexadecanoyl-CoA = (2E)-hexadecenoyl-CoA + H2O (RHEA:31163)
• (3S)-hydroxytetradecanoyl-CoA + NAD(+) = 3-oxotetradecanoyl-CoA + NADH + H(+) (RHEA:31167)
• (3S)-3-hydroxydodecanoyl-CoA + NAD(+) = 3-oxododecanoyl-CoA + NADH + H(+) (RHEA:31179)
• (3S)-hydroxydecanoyl-CoA + NAD(+) = 3-oxodecanoyl-CoA + NADH + H(+) (RHEA:31187)
• (3S)-hydroxyoctanoyl-CoA + NAD(+) = 3-oxooctanoyl-CoA + NADH + H(+) (RHEA:31195)
• (3S)-hydroxyoctanoyl-CoA = (2E)-octenoyl-CoA + H2O (RHEA:31199)
• 1’-[1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phospho]-3’-[1-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phospho]-glycerol + (9Z,12Z)-octadecadienoyl-CoA = 1’,3’-bis-[1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phospho]-glycerol + CoA (RHEA:43672)
• 1’-[1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phospho]-3’-[1-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phospho]-glycerol + (9Z)-octadecenoyl-CoA = 1’-[1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phospho]-3’-[1-(9Z,12Z-octadecadienoyl)-2-(9Z-octadecenoyl)-sn-glycero-3-phospho]-glycerol + CoA (RHEA:43676)

UniProt features (78 total): modified residue 56, sequence conflict 9, sequence variant 5, site 3, splice variant 2, transit peptide 1, chain 1, active site 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6DV2	X-RAY DIFFRACTION	3.6
5ZQZ	ELECTRON MICROSCOPY	4.2
5ZRV	ELECTRON MICROSCOPY	7.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P40939-F1	92.35	0.87

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 (4): 510 (for hydroxyacyl-coenzyme a dehydrogenase activity); 151 (important for long-chain enoyl-coa hydratase activity); 173 (important for long-chain enoyl-coa hydratase activity); 498 (important for hydroxyacyl-coenzyme a dehydrogenase activity)

Post-translational modifications (56): 129, 166, 166, 213, 214, 214, 230, 249, 249, 289, 295, 303, 303, 316, 326, 326, 334, 334, 350, 350 …

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-1482798	Acyl chain remodeling of CL
R-HSA-77285	Beta oxidation of myristoyl-CoA to lauroyl-CoA
R-HSA-77288	mitochondrial fatty acid beta-oxidation of unsaturated fatty acids
R-HSA-77305	Beta oxidation of palmitoyl-CoA to myristoyl-CoA
R-HSA-77310	Beta oxidation of lauroyl-CoA to decanoyl-CoA-CoA
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-77350	Beta oxidation of hexanoyl-CoA to butanoyl-CoA

MSigDB gene sets: 411 (showing top): GOBP_LIPID_MODIFICATION, MODULE_93, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_FATTY_ACID_CATABOLIC_PROCESS, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, MORF_HDAC1, DITTMER_PTHLH_TARGETS_UP, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLGLYCEROL_METABOLIC_PROCESS, KEGG_BIOSYNTHESIS_OF_UNSATURATED_FATTY_ACIDS, SHIPP_DLBCL_CURED_VS_FATAL_DN, KEGG_VALINE_LEUCINE_AND_ISOLEUCINE_DEGRADATION, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GTGCCTT_MIR506

GO Biological Process (5): fatty acid beta-oxidation (GO:0006635), response to insulin (GO:0032868), cardiolipin acyl-chain remodeling (GO:0035965), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631)

GO Molecular Function (13): (3S)-3-hydroxyacyl-CoA dehydrogenase (NAD+) activity (GO:0003857), acetyl-CoA C-acetyltransferase activity (GO:0003985), enoyl-CoA hydratase activity (GO:0004300), long-chain (3S)-3-hydroxyacyl-CoA dehydrogenase (NAD+) activity (GO:0016509), 3-hydroxyacyl-CoA dehydratase activity (GO:0018812), long-chain fatty acyl-CoA hydrolase activity (GO:0052816), NAD+ binding (GO:0070403), catalytic activity (GO:0003824), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor (GO:0016616), transferase activity (GO:0016740), lyase activity (GO:0016829)

GO Cellular Component (5): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial fatty acid beta-oxidation multienzyme complex (GO:0016507), mitochondrial nucleoid (GO:0042645), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
mitochondrial fatty acid beta-oxidation of saturated fatty acids	6
Glycerophospholipid biosynthesis	1
Mitochondrial Fatty Acid Beta-Oxidation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
catalytic activity	3
mitochondrion	2
mitochondrial matrix	2
fatty acid catabolic process	1
fatty acid ligase activity	1
fatty acid oxidation	1
response to peptide hormone	1
cardiolipin metabolic process	1
primary metabolic process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	1
acetyl-CoA C-acyltransferase activity	1
C-acetyltransferase activity	1
hydro-lyase activity	1
(3S)-3-hydroxyacyl-CoA dehydrogenase (NAD+) activity	1
enoyl-CoA hydratase activity	1
fatty acyl-CoA hydrolase activity	1
anion binding	1
NAD binding	1
molecular_function	1
binding	1
oxidoreductase activity, acting on CH-OH group of donors	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
fatty acid beta-oxidation multienzyme complex	1
mitochondrial protein-containing complex	1
nucleoid	1
intracellular membraneless organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

3366 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HADHA	HADHB	P55084	999
HADHA	ACAA2	P42765	962
HADHA	ACADVL	P49748	917
HADHA	ACAA1	P09110	893
HADHA	ACADL	P28330	885
HADHA	ACAD9	Q9H845	875
HADHA	ACADM	P11310	871
HADHA	ACAT1	P24752	862
HADHA	ACADS	P16219	822
HADHA	CPT1A	P50416	772
HADHA	CPT2	P23786	764
HADHA	ACSL1	P33121	720
HADHA	ACADSB	P45954	694
HADHA	CD36	P16671	640
HADHA	SLC25A20	O43772	634

IntAct

312 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
HADHA	HADHB	psi-mi:“MI:0407”(direct interaction)	0.870
HADHB	HADHA	psi-mi:“MI:0407”(direct interaction)	0.870
RELL2	OXSR1	psi-mi:“MI:0914”(association)	0.830
PKMYT1	CCNB2	psi-mi:“MI:0914”(association)	0.730
CDH1	CTNND1	psi-mi:“MI:0914”(association)	0.730
GABARAPL2	IPO5	psi-mi:“MI:0914”(association)	0.690
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
HADHA	GABARAP	psi-mi:“MI:0407”(direct interaction)	0.590
HADHA	GABARAP	psi-mi:“MI:0915”(physical association)	0.590
GABARAPL1	IPO5	psi-mi:“MI:0914”(association)	0.590
CANX	PGRMC1	psi-mi:“MI:0914”(association)	0.570
HADHA	HTT	psi-mi:“MI:0915”(physical association)	0.560
HADHA	CD74	psi-mi:“MI:0915”(physical association)	0.550
	HADHA	psi-mi:“MI:0915”(physical association)	0.540
	HADHA	psi-mi:“MI:0407”(direct interaction)	0.540
HADHB	POTEI	psi-mi:“MI:0914”(association)	0.530
PRKCZ	IPO5	psi-mi:“MI:0914”(association)	0.530
PDPK1	AGRN	psi-mi:“MI:0914”(association)	0.530
MINK1	CNOT1	psi-mi:“MI:0914”(association)	0.530
HADHA	MAP1LC3B	psi-mi:“MI:0407”(direct interaction)	0.520
MAP1LC3B	NIPSNAP2	psi-mi:“MI:0914”(association)	0.520

BioGRID (665): HADHA (Affinity Capture-MS), HADHA (Affinity Capture-MS), HADHA (Affinity Capture-MS), ATL3 (Co-fractionation), ATP1B1 (Co-fractionation), HADHA (Co-fractionation), HADHA (Co-fractionation), HADHB (Co-fractionation), NDUFB8 (Co-fractionation), TOMM40 (Co-fractionation), HADHA (Affinity Capture-MS), HADHA (Affinity Capture-RNA), HADHA (Affinity Capture-MS), HADHA (Affinity Capture-MS), HADHA (Affinity Capture-MS)

ESM2 similar proteins: A0A1S4CL59, A0A1S4D475, A0A1S4DF18, A0A1S4DFD3, A7M6E7, A7M6E8, A7SG73, A8XKG6, B2RFS9, B2RFT0, O04015, O04226, O65361, P22200, P32296, P40939, P43619, P49448, P54887, P54888, P56658, P93568, Q0E671, Q0IZS0, Q18164, Q29554, Q2QS13, Q2QS14, Q3SZM5, Q42806, Q42954, Q5R6R5, Q64428, Q6STH5, Q6Z836, Q8BMS1, Q8NFW8, Q8YNK2, Q90WG6, Q941T1

Diamond homologs: A0KV76, A1ADI8, A1JK30, A1RI92, A1S7L6, A3D684, A3QFP3, A4TM82, A4VKA3, A4WCW6, A4Y897, A5F2P2, A5W6H0, A5WH99, A6TC19, A6WQ25, A7FGK1, A7MH81, A7MS61, A7ZPF8, A8A2L0, A8ADP2, A8GH86, A9N453, B0KH74, B0TL21, B1IXA5, B1J5A5, B1LME7, B1X9L4, B2TWV4, B4SZR0, B4TCA8, B4TQC2, B5BBA1, B5EZR9, B5FPN1, B5R3R9, B5RCL3, B5XVW2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
HADHA	“form complex”	“Trifunctional enzyme”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 219 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
PINK1-PRKN Mediated Mitophagy	6	13.9×	7e-04
Selective autophagy	6	10.8×	2e-03
EPHB-mediated forward signaling	6	10.3×	3e-03
GPVI-mediated activation cascade	5	10.0×	7e-03
EPH-Ephrin signaling	9	9.7×	2e-04
Fcgamma receptor (FCGR) dependent phagocytosis	5	9.0×	1e-02
Macroautophagy	10	7.5×	2e-04
Autophagy	7	6.7×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
peptidyl-tyrosine phosphorylation	8	17.6×	2e-05
cellular response to amyloid-beta	6	12.3×	2e-03
mitophagy	7	11.7×	6e-04
cell-cell adhesion mediated by cadherin	5	10.8×	9e-03
obsolete positive regulation of NF-kappaB transcription factor activity	8	8.6×	9e-04
positive regulation of protein localization to plasma membrane	6	8.5×	7e-03
protein autophosphorylation	11	8.4×	4e-05
autophagosome assembly	7	8.2×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	59
Likely pathogenic	69
Uncertain significance	175
Likely benign	399
Benign	25

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1069465	NM_000182.5(HADHA):c.1990_1993dup (p.Ser665Ter)	Pathogenic
1070607	NC_000002.11:g.(?26416436)(26418111_?)del	Pathogenic
1071670	NM_000182.5(HADHA):c.294del (p.Phe98fs)	Pathogenic
1388408	NM_000182.5(HADHA):c.690del (p.Lys230fs)	Pathogenic
1408580	NM_000182.5(HADHA):c.352_353del (p.Gln118fs)	Pathogenic
1427255	NM_000182.5(HADHA):c.2208T>A (p.Tyr736Ter)	Pathogenic
1435055	NM_000182.5(HADHA):c.310dup (p.Ile104fs)	Pathogenic
1452112	NM_000182.5(HADHA):c.2020C>T (p.Gln674Ter)	Pathogenic
1452124	NM_000182.5(HADHA):c.1554del (p.Asp520fs)	Pathogenic
1452307	NM_000182.5(HADHA):c.1620+1del	Pathogenic
1452699	NM_000182.5(HADHA):c.387_388del (p.Lys129fs)	Pathogenic
1454661	NC_000002.11:g.(?26414109)(26415303_?)del	Pathogenic
1455608	NM_000182.5(HADHA):c.1204C>T (p.Gln402Ter)	Pathogenic
1460437	NC_000002.11:g.(?26467378)(26467464_?)del	Pathogenic
1695860	NM_000182.5(HADHA):c.918+2T>A	Pathogenic
189105	NM_000182.5(HADHA):c.274_278del (p.Ser92fs)	Pathogenic
1994476	NM_000182.5(HADHA):c.156_157del (p.Arg53fs)	Pathogenic
2028098	NM_000182.5(HADHA):c.238del (p.Trp80fs)	Pathogenic
203747	NM_000182.5(HADHA):c.1668_1674dup (p.Ile559Ter)	Pathogenic
2046757	NM_000182.5(HADHA):c.1336G>T (p.Glu446Ter)	Pathogenic
2107593	NM_000182.5(HADHA):c.469C>T (p.Gln157Ter)	Pathogenic
2113521	NM_000182.5(HADHA):c.703_704dup (p.Thr236fs)	Pathogenic
2134388	NM_000182.5(HADHA):c.1209del (p.Val404fs)	Pathogenic
2179378	NM_000182.5(HADHA):c.2167_2168dup (p.Tyr724fs)	Pathogenic
2422548	NC_000002.11:g.(?26416426)(26418121_?)del	Pathogenic
2422549	NC_000002.11:g.(?26414119)(26462031_?)del	Pathogenic
2675966	NM_000182.5(HADHA):c.315-2A>T	Pathogenic
2928078	NM_000182.5(HADHA):c.893del (p.Tyr298fs)	Pathogenic
2935068	NM_000182.5(HADHA):c.1261G>T (p.Glu421Ter)	Pathogenic
2937105	NM_000182.5(HADHA):c.70dup (p.Tyr24fs)	Pathogenic

SpliceAI

2614 predictions. Top by Δscore:

Variant	Effect	Δscore
2:26191394:CC:C	acceptor_gain	1.0000
2:26191395:CC:C	acceptor_gain	1.0000
2:26191395:CCTGA:C	acceptor_loss	1.0000
2:26191396:C:CC	acceptor_gain	1.0000
2:26191396:CT:C	acceptor_loss	1.0000
2:26191397:T:A	acceptor_loss	1.0000
2:26191484:T:TA	donor_gain	1.0000
2:26191485:C:A	donor_gain	1.0000
2:26191530:C:CA	donor_gain	1.0000
2:26191629:C:CC	acceptor_gain	1.0000
2:26192305:CTTA:C	donor_loss	1.0000
2:26192306:TTAC:T	donor_loss	1.0000
2:26192307:TA:T	donor_loss	1.0000
2:26192308:A:AC	donor_gain	1.0000
2:26192308:ACACT:A	donor_loss	1.0000
2:26192309:C:CA	donor_loss	1.0000
2:26192309:C:CC	donor_gain	1.0000
2:26192309:CA:C	donor_gain	1.0000
2:26192309:CACT:C	donor_gain	1.0000
2:26192309:CACTT:C	donor_gain	1.0000
2:26192423:ACC:A	acceptor_loss	1.0000
2:26192425:C:CC	acceptor_gain	1.0000
2:26192425:CTAA:C	acceptor_loss	1.0000
2:26192426:T:G	acceptor_loss	1.0000
2:26193572:CTCA:C	donor_loss	1.0000
2:26193573:TCA:T	donor_loss	1.0000
2:26193574:CAC:C	donor_loss	1.0000
2:26193575:A:AC	donor_gain	1.0000
2:26193576:C:CC	donor_gain	1.0000
2:26193716:C:CT	acceptor_gain	1.0000

AlphaMissense

4956 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:26191509:C:T	G707E	0.999
2:26194613:C:A	R549M	0.999
2:26194624:G:C	F545L	0.999
2:26194624:G:T	F545L	0.999
2:26194626:A:G	F545L	0.999
2:26195186:A:G	L509P	0.999
2:26195212:G:C	F500L	0.999
2:26195212:G:T	F500L	0.999
2:26195214:A:G	F500L	0.999
2:26195220:G:C	H498D	0.999
2:26197745:G:C	N475K	0.999
2:26197745:G:T	N475K	0.999
2:26197748:A:C	S474R	0.999
2:26197748:A:T	S474R	0.999
2:26197750:T:G	S474R	0.999
2:26201176:C:A	K455N	0.999
2:26201176:C:G	K455N	0.999
2:26234235:G:C	C145W	0.999
2:26191521:C:T	G703E	0.998
2:26193697:C:G	D589H	0.998
2:26193702:A:G	L587P	0.998
2:26194612:C:A	R549S	0.998
2:26194612:C:G	R549S	0.998
2:26194613:C:G	R549T	0.998
2:26195126:C:T	G529D	0.998
2:26195183:T:A	E510V	0.998
2:26195189:A:G	L508P	0.998
2:26195218:G:C	H498Q	0.998
2:26195218:G:T	H498Q	0.998
2:26191499:G:C	F710L	0.997

dbSNP variants (sampled 300 via entrez): RS1000037528 (2:26193496 C>T), RS1000056377 (2:26197949 C>T), RS1000126643 (2:26244821 G>A), RS1000165142 (2:26246013 G>C), RS1000185624 (2:26190517 C>T), RS1000219953 (2:26204876 T>C), RS1000272229 (2:26190360 T>A,C), RS1000297620 (2:26192008 G>A,T), RS1000304056 (2:26238613 T>C), RS1000311962 (2:26239866 T>C), RS1000437896 (2:26211935 T>G), RS1000441713 (2:26245261 GGGGT>G,GGGGTGGGT), RS1000443395 (2:26211477 C>T), RS1000475423 (2:26195956 C>T), RS1000567035 (2:26203173 G>A)

Disease associations

OMIM: gene MIM:600890 | disease phenotypes: MIM:609015, MIM:609016

GenCC curated gene-disease

Disease	Classification	Inheritance
long chain 3-hydroxyacyl-CoA dehydrogenase deficiency	Definitive	Autosomal recessive
mitochondrial trifunctional protein deficiency	Strong	Autosomal recessive
mitochondrial trifunctional protein deficiency 1	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
long chain 3-hydroxyacyl-CoA dehydrogenase deficiency	Definitive	AR

Mondo (3): mitochondrial trifunctional protein deficiency (MONDO:0012172), long chain 3-hydroxyacyl-CoA dehydrogenase deficiency (MONDO:0012173), mitochondrial trifunctional protein deficiency 1 (MONDO:0958181)

Orphanet (2): Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency (Orphanet:5), Mitochondrial trifunctional protein deficiency (Orphanet:746)

HPO phenotypes

87 total (30 of 87 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000488	Retinopathy
HP:0000512	Abnormal electroretinogram
HP:0000532	Abnormal chorioretinal morphology
HP:0000533	Chorioretinal atrophy
HP:0000545	Myopia
HP:0000572	Visual loss
HP:0000577	Exotropia
HP:0000580	Pigmentary retinopathy
HP:0000613	Photophobia
HP:0000662	Nyctalopia
HP:0000829	Hypoparathyroidism
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001254	Lethargy
HP:0001259	Coma
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001284	Areflexia
HP:0001290	Generalized hypotonia
HP:0001324	Muscle weakness
HP:0001396	Cholestasis
HP:0001508	Failure to thrive
HP:0001518	Small for gestational age
HP:0001531	Failure to thrive in infancy
HP:0001560	Abnormality of the amniotic fluid
HP:0001635	Congestive heart failure
HP:0001638	Cardiomyopathy
HP:0001639	Hypertrophic cardiomyopathy

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C566945	Trifunctional Protein Deficiency With Myopathy And Neuropathy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295759 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs771622695	HADHA		0.00	0

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.23	Kd	59.46	nM	CHEMBL5653589
7.23	ED50	59.46	nM	CHEMBL5653589
6.06	Kd	877.1	nM	CHEMBL3752910
6.06	ED50	877.1	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 7 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148482: Binding affinity to human HADHA incubated for 45 mins by Kinobead based pull down assay	kd	0.0595	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148482: Binding affinity to human HADHA incubated for 45 mins by Kinobead based pull down assay	kd	0.8771	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
perfluorooctanoic acid	increases expression	4
perfluorooctane sulfonic acid	affects expression, increases expression	4
bisphenol A	decreases expression, increases expression	3
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, affects expression	2
Ozone	increases oxidation, increases abundance, affects expression, affects cotreatment	2
Valproic Acid	affects expression, decreases methylation	2
Cyclosporine	decreases expression	2
Oleic Acid	affects cotreatment, increases expression, decreases expression, increases reaction, decreases reaction (+1 more)	2
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
perfluorodecanesulfonic acid	increases expression	1
intybin	decreases expression, decreases reaction, affects cotreatment, increases abundance	1
quinone	decreases expression, decreases reaction	1
2,4,6-tribromophenol	decreases expression	1
testosterone enanthate	affects expression	1
lasiocarpine	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
fenofibric acid	affects binding, increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression, increases expression	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	increases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
pyrrolidine dithiocarbamic acid	affects cotreatment, decreases reaction, increases expression	1
gossypol acetic acid	decreases expression	1
bathocuproine sulfonate	affects cotreatment, decreases reaction, increases expression	1
perfluorodecanoic acid	affects expression	1
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	1
ciglitazone	affects binding, increases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118666	Binding	Binding affinity to HADHA 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

6 cell lines: 2 finite cell line, 2 cancer cell line, 1 induced pluripotent stem cell, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A5VU	ICGi028-A	Induced pluripotent stem cell	Male
CVCL_B2YH	Abcam HEK293T HADHA KO	Transformed cell line	Female
CVCL_CW81	GM07843	Finite cell line	Female
CVCL_IJ42	GM20266	Finite cell line	Female
CVCL_SQ85	HAP1 HADHA (-) 1	Cancer cell line	Male
CVCL_SQ86	HAP1 HADHA (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01379625	PHASE2	COMPLETED	Study of Triheptanoin for Treatment of Long-Chain Fatty Acid Oxidation Disorder
NCT01494051	PHASE1/PHASE2	COMPLETED	High Protein Diet in Patients With Long-chain Fatty Acid Oxidation Disorders
NCT05411835	EARLY_PHASE1	COMPLETED	Oral Ketones and Exercise Among Patients With Long-chain Fatty Acid Oxidation Disorders
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
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
NCT00840112	Not specified	TERMINATED	Vitamin E Treatment for Long-Chain 3-Hydroxyacyl Coenzyme A (CoA) Dehydrogenase (LCHAD) Associated Neuropathy
NCT01461304	Not specified	NO_LONGER_AVAILABLE	Compassionate Use of Triheptanoin (C7) for Inherited Disorders of Energy Metabolism