OXCT1

Summary

OXCT1 (3-oxoacid CoA-transferase 1, HGNC:8527) is a protein-coding gene on chromosome 5p13.1, encoding Succinyl-CoA:3-ketoacid coenzyme A transferase 1, mitochondrial (P55809). Key enzyme for ketone body catabolism.

This gene encodes a member of the 3-oxoacid CoA-transferase gene family. The encoded protein is a homodimeric mitochondrial matrix enzyme that plays a central role in extrahepatic ketone body catabolism by catalyzing the reversible transfer of coenzyme A from succinyl-CoA to acetoacetate. Mutations in this gene are associated with succinyl CoA:3-oxoacid CoA transferase deficiency.

Source: NCBI Gene 5019 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial disease (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 257 total — 9 pathogenic, 12 likely-pathogenic
• Phenotypes (HPO): 18
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_000436

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8527
Approved symbol	OXCT1
Name	3-oxoacid CoA-transferase 1
Location	5p13.1
Locus type	gene with protein product
Status	Approved
Aliases	SCOT
Ensembl gene	ENSG00000083720
Ensembl biotype	protein_coding
OMIM	601424
Entrez	5019

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 15 protein_coding, 2 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000196371, ENST00000503374, ENST00000508557, ENST00000509987, ENST00000510634, ENST00000512084, ENST00000513081, ENST00000514723, ENST00000899738, ENST00000899739, ENST00000899740, ENST00000919063, ENST00000972068, ENST00000972069, ENST00000972070, ENST00000972071, ENST00000972072, ENST00000972073, ENST00000972074

RefSeq mRNA: 6 — MANE Select: NM_000436 NM_000436, NM_001364299, NM_001364300, NM_001364301, NM_001364302, NM_001364303

CCDS: CCDS3937, CCDS93708

Canonical transcript exons

ENST00000196371 — 17 exons

Exon	Start	End
ENSE00000742476	41805567	41805681
ENSE00000742478	41807331	41807438
ENSE00000742482	41842675	41842781
ENSE00000971109	41861314	41861404
ENSE00000971112	41803069	41803163
ENSE00001134797	41794677	41794749
ENSE00001134811	41801022	41801070
ENSE00001134863	41850030	41850179
ENSE00001134870	41853419	41853554
ENSE00001134888	41862642	41862750
ENSE00001142959	41730065	41731770
ENSE00001142971	41870281	41870425
ENSE00003529891	41739390	41739491
ENSE00003538865	41762111	41762200
ENSE00003579269	41840451	41840511
ENSE00003681944	41749527	41749607
ENSE00003684066	41794003	41794078

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 98.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.9255 / max 861.2169, expressed in 1740 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
61485	20.2152	1669
61483	8.3591	1512
61487	3.3029	1154
61484	3.2383	1237
61488	2.0813	1098
61478	0.3505	208
61486	0.3488	180
61477	0.0295	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	98.92	gold quality
heart right ventricle	UBERON:0002080	98.68	gold quality
endothelial cell	CL:0000115	98.13	gold quality
myocardium	UBERON:0002349	98.13	gold quality
middle temporal gyrus	UBERON:0002771	97.89	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.64	gold quality
calcaneal tendon	UBERON:0003701	97.56	gold quality
orbitofrontal cortex	UBERON:0004167	97.07	gold quality
Brodmann (1909) area 46	UBERON:0006483	96.70	gold quality
superior frontal gyrus	UBERON:0002661	96.61	gold quality
cardiac ventricle	UBERON:0002082	96.48	gold quality
heart left ventricle	UBERON:0002084	96.43	gold quality
postcentral gyrus	UBERON:0002581	96.36	gold quality
tibia	UBERON:0000979	96.30	gold quality
parietal lobe	UBERON:0001872	95.76	gold quality
prefrontal cortex	UBERON:0000451	95.70	gold quality
entorhinal cortex	UBERON:0002728	95.52	gold quality
heart	UBERON:0000948	95.42	gold quality
cardiac atrium	UBERON:0002081	95.39	gold quality
right atrium auricular region	UBERON:0006631	95.21	gold quality
lateral nuclear group of thalamus	UBERON:0002736	95.05	gold quality
diaphragm	UBERON:0001103	94.95	gold quality
frontal cortex	UBERON:0001870	94.67	gold quality
frontal lobe	UBERON:0016525	94.67	gold quality
esophagus squamous epithelium	UBERON:0006920	94.61	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.50	gold quality
parotid gland	UBERON:0001831	94.49	gold quality
renal medulla	UBERON:0000362	94.36	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.23	gold quality
neocortex	UBERON:0001950	94.13	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.37

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SP1

miRNA regulators (miRDB)

73 targeting OXCT1, 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-3646	100.00	73.56	5283
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-7106-5P	99.53	67.47	3574

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 14)

• Results demonstrate that h-Scot-t is a single intronless gene specifically expressed in the testis. (PMID:11756565)
• In SCOT-deficient patients retaining some residual activity, permanent ketosis may be absent. (PMID:15496607)
• A 6-bp deletion at the splice donor site of intron 1 resulted in the absence of a full-length mature SCOT mRNA with faint amounts of aberrantly spliced transcripts using a cryptic splice donor site within exon 1. (PMID:16765626)
• the R268H mutation is a ketoacidosis-causing one (PMID:17706444)
• liver-specific silencing of the SCOT gene expression may be mediated in part by its 5’-flanking sequence (PMID:18648183)
• The activities of pyruvate carboxylase (SCOT) were decreased by 65% in pancreatic islets of patients with type 2 diabetes. (PMID:19296078)
• This protein has been found differentially expressed in the anterior cingulate cortex from patients with schizophrenia (PMID:20381070)
• Case Report: Succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency causes episodic ketoacidotic crises and no apparent symptoms between them. (PMID:20652411)
• Missense Mutations in succinyl-CoA:3-ketoacid CoA transferase is associated with Ketoacidosis. (PMID:21296660)
• Data show that the ketone body metabolizing enzymes BDH1, BDH2, OXCT1 and ACAT1 were expressed at the mRNA and protein level in all glioma cell lines. (PMID:21791085)
• Crystal structure of human SCOT, providing a molecular understanding of the reported mutations based on their potential structural effects. (PMID:23420214)
• Succinyl-CoA:3-oxoacid coenzyme A transferase (SCOT) deficiency: A rare and potentially fatal metabolic disease. (PMID:33596448)
• Identifying Acss1, Mtfp1 and Oxct1 as key regulators and promising biomarkers of sarcopenia in various models. (PMID:38042218)
• OXCT1 functions as a succinyltransferase, contributing to hepatocellular carcinoma via succinylating LACTB. (PMID:38176415)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	oxct1a	ENSDARG00000013063
danio_rerio	oxct1b	ENSDARG00000054319
mus_musculus	Oxct1	ENSMUSG00000022186
rattus_norvegicus	Oxct1	ENSRNOG00000043094
drosophila_melanogaster	SCOT	FBGN0035298
caenorhabditis_elegans		WBGENE00007330

Paralogs (1): OXCT2 (ENSG00000198754)

Protein

Protein identifiers

Succinyl-CoA:3-ketoacid coenzyme A transferase 1, mitochondrial — P55809 (reviewed: P55809)

Alternative names: 3-oxoacid CoA-transferase 1, Somatic-type succinyl-CoA:3-oxoacid CoA-transferase, Succinyl-CoA:3-oxoacid CoA transferase

All UniProt accessions (3): P55809, A0A024R040, E9PDW2

UniProt curated annotations — full annotation on UniProt →

Function. Key enzyme for ketone body catabolism. Catalyzes the first, rate-limiting step of ketone body utilization in extrahepatic tissues, by transferring coenzyme A (CoA) from a donor thiolester species (succinyl-CoA) to an acceptor carboxylate (acetoacetate), and produces acetoacetyl-CoA. Acetoacetyl-CoA is further metabolized by acetoacetyl-CoA thiolase into two acetyl-CoA molecules which enter the citric acid cycle for energy production. Forms a dimeric enzyme where both of the subunits are able to form enzyme-CoA thiolester intermediates, but only one subunit is competent to transfer the CoA moiety to the acceptor carboxylate (3-oxo acid) and produce a new acyl-CoA. Formation of the enzyme-CoA intermediate proceeds via an unstable anhydride species formed between the carboxylate groups of the enzyme and substrate.

Subunit / interactions. Homodimer. Only one subunit is competent to transfer the CoA moiety to the acceptor carboxylate (3-oxo acid).

Subcellular location. Mitochondrion.

Tissue specificity. Abundant in heart, followed in order by brain, kidney, skeletal muscle, and lung, whereas in liver it is undetectable. Expressed (at protein level) in all tissues (except in liver), most abundant in myocardium, then brain, kidney, adrenal glands, skeletal muscle and lung; also detectable in leukocytes and fibroblasts.

Disease relevance. Succinyl-CoA:3-oxoacid CoA transferase deficiency (SCOTD) [MIM:245050] A disorder of ketone body metabolism, characterized by episodic ketoacidosis. Patients are usually asymptomatic between episodes. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Ketone metabolism; succinyl-CoA degradation; acetoacetyl-CoA from succinyl-CoA: step 1/1.

Similarity. Belongs to the 3-oxoacid CoA-transferase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P55809-1	1	yes
P55809-2	2

RefSeq proteins (6): NP_000427, NP_001351228, NP_001351229, NP_001351230, NP_001351231, NP_001351232 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004163	CoA_transf_BS	Binding_site
IPR004164	CoA_transf_AS	Active_site
IPR004165	CoA_trans_fam_I	Family
IPR012791	3-oxoacid_CoA-transf_B	Domain
IPR012792	3-oxoacid_CoA-transf_A	Domain
IPR014388	3-oxoacid_CoA-transferase	Family
IPR037171	NagB/RpiA_transferase-like	Homologous_superfamily

Pfam: PF01144

Enzyme classification (BRENDA):

• EC 2.8.3.5 — 3-oxoacid CoA-transferase (BRENDA: 20 organisms, 33 substrates, 60 inhibitors, 44 Km, 8 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ACETOACETATE	0.0002–0.44	13
ACETOACETYL-COA	0.006–0.72	10
SUCCINATE	0.025–39	9
SUCCINYL-COA	0.156–8	9
MALEATE	35	1

Catalyzed reactions (Rhea), 2 shown:

• a 3-oxo acid + succinyl-CoA = a 3-oxoacyl-CoA + succinate (RHEA:24564)
• acetoacetate + succinyl-CoA = acetoacetyl-CoA + succinate (RHEA:25480)

UniProt features (80 total): strand 30, helix 19, sequence variant 17, modified residue 5, turn 4, transit peptide 1, chain 1, active site 1, sequence conflict 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3DLX	X-RAY DIFFRACTION	2.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P55809-F1	92.33	0.88

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): 344 (5-glutamyl coenzyme a thioester intermediate)

Post-translational modifications (5): 170, 185, 418, 421, 455

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-77108	Utilization of Ketone Bodies
R-HSA-9837999	Mitochondrial protein degradation
R-HSA-1430728	Metabolism
R-HSA-392499	Metabolism of proteins
R-HSA-556833	Metabolism of lipids
R-HSA-74182	Ketone body metabolism

MSigDB gene sets: 330 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, GOBP_RESPONSE_TO_ETHANOL, GOBP_INSULIN_SECRETION, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_HORMONE_TRANSPORT, RIZKI_TUMOR_INVASIVENESS_3D_DN, MODULE_16, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_KETONE_METABOLIC_PROCESS, KEGG_VALINE_LEUCINE_AND_ISOLEUCINE_DEGRADATION, RODWELL_AGING_KIDNEY_NO_BLOOD_DN, GOBP_CELL_CELL_SIGNALING, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY

GO Biological Process (13): heart development (GO:0007507), response to nutrient (GO:0007584), response to xenobiotic stimulus (GO:0009410), response to hormone (GO:0009725), response to activity (GO:0014823), positive regulation of insulin secretion involved in cellular response to glucose stimulus (GO:0035774), ketone catabolic process (GO:0042182), response to starvation (GO:0042594), response to ethanol (GO:0045471), ketone body catabolic process (GO:0046952), adipose tissue development (GO:0060612), obsolete ketone body metabolic process (GO:1902224), lipid metabolic process (GO:0006629)

GO Molecular Function (4): succinyl-CoA:3-oxo-acid CoA-transferase activity (GO:0008260), identical protein binding (GO:0042802), CoA-transferase activity (GO:0008410), transferase activity (GO:0016740)

GO Cellular Component (2): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Ketone body metabolism	1
Metabolism of proteins	1
Metabolism	1
Metabolism of lipids	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to chemical	3
animal organ development	2
response to nutrient levels	2
small molecule catabolic process	2
circulatory system development	1
response to endogenous stimulus	1
response to stimulus	1
positive regulation of insulin secretion	1
insulin secretion involved in cellular response to glucose stimulus	1
regulation of insulin secretion involved in cellular response to glucose stimulus	1
ketone metabolic process	1
response to stress	1
response to alcohol	1
fatty acid derivative catabolic process	1
connective tissue development	1
primary metabolic process	1
CoA-transferase activity	1
protein binding	1
transferase activity, transferring sulphur-containing groups	1
catalytic activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

1500 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OXCT1	BDH1	Q02338	824
OXCT1	ACAT1	P24752	761
OXCT1	HMGCL	P35914	732
OXCT1	HMGCS2	P54868	688
OXCT1	ACAA2	P42765	637
OXCT1	BMP8B	P34820	588
OXCT1	BDH2	Q9BUT1	575
OXCT1	HMGCS1	Q01581	565
OXCT1	AACS	Q86V21	557
OXCT1	HMGCLL1	Q8TB92	539
OXCT1	TEKT1	Q969V4	532
OXCT1	HADHB	P55084	503
OXCT1	ACAT2	Q9BWD1	498
OXCT1	HADHA	P40939	496
OXCT1	CS	O75390	491
OXCT1	ENO1	P06733	491

IntAct

41 interactions, top by confidence:

A	B	Type	Score
NDUFS3	NDUFS8	psi-mi:“MI:0914”(association)	0.730
OXCT1	EPS15	psi-mi:“MI:0914”(association)	0.530
BMP2K	OXCT1	psi-mi:“MI:0915”(physical association)	0.400
ADGRB3	OXCT1	psi-mi:“MI:0915”(physical association)	0.400
SPRYD4	OXCT1	psi-mi:“MI:0915”(physical association)	0.400
PSEN1	OXCT1	psi-mi:“MI:0915”(physical association)	0.370
NDUFV1	NDUFS8	psi-mi:“MI:0914”(association)	0.350
BCL2L14		psi-mi:“MI:0914”(association)	0.350
OXCT1	BCKDHA	psi-mi:“MI:0914”(association)	0.350
PAK5	IDE	psi-mi:“MI:0914”(association)	0.350
OXCT1	SLC25A5	psi-mi:“MI:0914”(association)	0.350
PAK5	COQ9	psi-mi:“MI:0914”(association)	0.350
FMC1	NDUFAB1	psi-mi:“MI:0914”(association)	0.350
OXCT1	COQ9	psi-mi:“MI:0914”(association)	0.350
PRSS35	NDUFAB1	psi-mi:“MI:0914”(association)	0.350
PTPMT1	NDUFAB1	psi-mi:“MI:0914”(association)	0.350
FMC1	POLRMT	psi-mi:“MI:0914”(association)	0.350
ZDHHC5	IGKV2D-24	psi-mi:“MI:0914”(association)	0.350
JAZF1	TNPO2	psi-mi:“MI:0914”(association)	0.350
IQCB1	PCP4L1	psi-mi:“MI:0914”(association)	0.350
MAPT	SEPTIN8	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
SLC25A16	TOMM70	psi-mi:“MI:0914”(association)	0.350
GATA2	EFCAB5	psi-mi:“MI:0914”(association)	0.350

BioGRID (150): AHNAK (Co-fractionation), FH (Co-fractionation), HINT1 (Co-fractionation), HSPB1 (Co-fractionation), LYPLA1 (Co-fractionation), MDH1 (Co-fractionation), OXCT1 (Co-fractionation), RAE1 (Co-fractionation), SOD1 (Co-fractionation), TALDO1 (Co-fractionation), TPI1 (Co-fractionation), OXCT1 (Affinity Capture-MS), OXCT1 (Affinity Capture-MS), OXCT1 (Affinity Capture-MS), OXCT2 (Affinity Capture-MS)

ESM2 similar proteins: A0QMH2, A5W7G2, B0KTX5, B0RVK3, B0RVK4, B0U5G3, B2GV06, B2I9S0, B3EY95, F1CYZ5, O34317, P0C7I7, P0C7I8, P42315, P44875, P52043, P55809, P56006, P63649, P63651, P65155, P75726, P76458, P76459, P9WKJ4, P9WKJ5, P9WPW0, P9WPW1, P9WPW2, P9WPW3, P9WPW4, P9WPW5, Q01103, Q09450, Q20Z21, Q29551, Q43973, Q4CY36, Q4K8M6, Q73TT7

Diamond homologs: B0RVK3, B2GV06, O34466, P0A101, P0A102, P0C7I8, P23673, P42316, P44874, P55809, P56007, P63651, P76459, P9WPW2, P9WPW3, Q09450, Q29551, Q54JD9, Q59091, Q5XIJ9, Q9BYC2, Q9D0K2, Q9ESL0, Q9JJN4, Q9W058, Q9ZLE4, B0RVK4, O34317, P0C7I7, P33752, P42315, P44875, P56006, P63649, P76458, P9WPW4, P9WPW5, Q01103, Q43973, Q9ZLE3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 44 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
Mitochondrial protein degradation	6	22.8×	3e-05

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial electron transport, NADH to ubiquinone	5	48.5×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	12
Uncertain significance	103
Likely benign	65
Benign	37

Top pathogenic / likely-pathogenic (21)

Variant ID	HGVS	Classification
1064695	NM_000436.4(OXCT1):c.1370C>T (p.Thr457Ile)	Pathogenic
1071420	NM_000436.4(OXCT1):c.803G>A (p.Arg268His)	Pathogenic
1071421	NM_000436.4(OXCT1):c.649C>T (p.Arg217Ter)	Pathogenic
1686001	NM_000436.4(OXCT1):c.733-2A>G	Pathogenic
1705309	NM_000436.4(OXCT1):c.1419+1G>C	Pathogenic
8163	NM_000436.4(OXCT1):c.848C>G (p.Ser283Ter)	Pathogenic
8164	NM_000436.4(OXCT1):c.1367G>T (p.Cys456Phe)	Pathogenic
8166	NM_000436.4(OXCT1):c.971G>A (p.Gly324Glu)	Pathogenic
8167	NM_000436.4(OXCT1):c.656G>A (p.Gly219Glu)	Pathogenic
1324840	NM_000436.4(OXCT1):c.278+1G>A	Likely pathogenic
1324841	NM_000436.4(OXCT1):c.450dup (p.Gly151fs)	Likely pathogenic
3062096	NM_000436.4(OXCT1):c.1456_1457del (p.Leu486fs)	Likely pathogenic
3345075	NM_000436.4(OXCT1):c.1063C>T (p.Arg355Ter)	Likely pathogenic
3384092	NM_000436.4(OXCT1):c.1286dup (p.Leu429fs)	Likely pathogenic
353659	NM_000436.4(OXCT1):c.1099+2T>C	Likely pathogenic
41497	NM_000436.4(OXCT1):c.1248+5G>A	Likely pathogenic
631482	NM_000436.4(OXCT1):c.424G>C (p.Ala142Pro)	Likely pathogenic
800772	NM_000436.4(OXCT1):c.1402C>T (p.Arg468Cys)	Likely pathogenic
802120	NM_000436.4(OXCT1):c.193G>A (p.Gly65Arg)	Likely pathogenic
828111	NM_000436.4(OXCT1):c.370C>T (p.Arg124Ter)	Likely pathogenic
973561	NM_000436.4(OXCT1):c.1339-2A>G	Likely pathogenic

SpliceAI

3171 predictions. Top by Δscore:

Variant	Effect	Δscore
5:41739382:ATACT:A	donor_loss	1.0000
5:41739383:TACTT:T	donor_loss	1.0000
5:41739385:CT:C	donor_loss	1.0000
5:41739386:TTA:T	donor_loss	1.0000
5:41739387:TA:T	donor_loss	1.0000
5:41739388:A:AC	donor_gain	1.0000
5:41739388:ACT:A	donor_loss	1.0000
5:41739388:ACTG:A	donor_gain	1.0000
5:41739389:C:CA	donor_gain	1.0000
5:41739389:CT:C	donor_gain	1.0000
5:41739389:CTG:C	donor_gain	1.0000
5:41739389:CTGC:C	donor_gain	1.0000
5:41739389:CTGCA:C	donor_gain	1.0000
5:41739487:ACAGC:A	acceptor_gain	1.0000
5:41739488:CAGC:C	acceptor_gain	1.0000
5:41739488:CAGCC:C	acceptor_gain	1.0000
5:41739489:AGC:A	acceptor_gain	1.0000
5:41739489:AGCC:A	acceptor_loss	1.0000
5:41739490:GC:G	acceptor_gain	1.0000
5:41739491:CC:C	acceptor_gain	1.0000
5:41739492:C:CA	acceptor_loss	1.0000
5:41739492:C:CC	acceptor_gain	1.0000
5:41739496:C:CT	acceptor_gain	1.0000
5:41739497:A:T	acceptor_gain	1.0000
5:41739500:G:C	acceptor_gain	1.0000
5:41739500:G:GC	acceptor_gain	1.0000
5:41749523:TTACC:T	donor_loss	1.0000
5:41749524:TACCT:T	donor_loss	1.0000
5:41749525:ACCT:A	donor_loss	1.0000
5:41749526:CC:C	donor_loss	1.0000

AlphaMissense

3401 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:41762167:C:G	D428H	1.000
5:41762178:C:A	G424V	1.000
5:41762178:C:T	G424E	1.000
5:41762179:C:G	G424R	1.000
5:41762179:C:T	G424R	1.000
5:41762184:C:T	G422E	1.000
5:41762185:C:G	G422R	1.000
5:41762185:C:T	G422R	1.000
5:41794014:A:G	W413R	1.000
5:41794014:A:T	W413R	1.000
5:41794015:G:C	N412K	1.000
5:41794015:G:T	N412K	1.000
5:41794052:C:T	G400E	1.000
5:41794691:A:C	F386L	1.000
5:41794691:A:T	F386L	1.000
5:41794693:A:G	F386L	1.000
5:41803088:T:A	E344V	1.000
5:41803148:C:T	G324E	1.000
5:41803154:C:T	G322D	1.000
5:41850179:C:G	G139R	1.000
5:41853419:C:A	Q138H	1.000
5:41853419:C:G	Q138H	1.000
5:41861400:A:C	F64L	1.000
5:41861400:A:T	F64L	1.000
5:41861402:A:G	F64L	1.000
5:41749593:T:A	K451N	0.999
5:41749593:T:G	K451N	0.999
5:41749595:T:C	K451E	0.999
5:41762133:A:T	V439D	0.999
5:41762163:A:G	L429S	0.999

dbSNP variants (sampled 300 via entrez): RS1000002259 (5:41757913 T>G), RS1000035536 (5:41823379 C>G), RS1000036569 (5:41736937 A>C), RS1000066282 (5:41827946 C>G), RS1000082623 (5:41781339 T>G), RS1000088214 (5:41856783 G>A), RS1000104020 (5:41855225 G>A), RS1000144224 (5:41833133 A>C), RS1000154274 (5:41798879 G>A), RS1000209001 (5:41765107 C>A), RS1000219281 (5:41826228 T>C), RS1000223442 (5:41846108 TTATG>T,TTATGTATG), RS1000254087 (5:41777804 C>A,G), RS1000254684 (5:41826513 G>A), RS1000333643 (5:41729820 A>G)

Disease associations

OMIM: gene MIM:601424 | disease phenotypes: MIM:245050

GenCC curated gene-disease

Disease	Classification	Inheritance
succinyl-CoA:3-ketoacid CoA transferase deficiency	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
mitochondrial disease	Definitive	AR

Mondo (1): succinyl-CoA:3-ketoacid CoA transferase deficiency (MONDO:0009492)

Orphanet (1): Succinyl-CoA:3-oxoacid CoA transferase deficiency (Orphanet:832)

HPO phenotypes

18 total (18 of 18 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001252	Hypotonia
HP:0001254	Lethargy
HP:0001259	Coma
HP:0001531	Failure to thrive in infancy
HP:0001640	Cardiomegaly
HP:0001944	Dehydration
HP:0001993	Ketoacidosis
HP:0002013	Vomiting
HP:0002018	Nausea
HP:0002789	Tachypnea
HP:0002919	Ketonuria
HP:0003623	Neonatal onset
HP:0004325	Decreased body weight
HP:0005974	Episodic ketoacidosis
HP:0040155	Elevated urinary 3-hydroxybutyric acid
HP:0410175	Hyperketonemia
HP:6000361	Reduced succinyl-CoA:3-oxoacid-CoA transferase activity in cultured fibroblasts

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST008607_1	Ketonuria	2.000000e-16
GCST008608_1	Ketonuria (moderate to severe)	1.000000e-15
GCST008609_1	Ketonuria (mild)	2.000000e-06

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537527	Succinyl-CoA:3-oxoacid CoA transferase deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation, affects cotreatment	4
sodium arsenite	decreases expression, increases expression	3
Benzo(a)pyrene	decreases expression, decreases methylation, increases expression	3
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Cisplatin	affects cotreatment, decreases expression, increases expression	2
Fluorouracil	affects reaction, decreases expression, affects response to substance	2
Rotenone	increases expression, decreases expression	2
Tretinoin	decreases expression	2
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
propionaldehyde	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, increases expression	1
terbufos	increases methylation	1
cobaltous chloride	decreases expression	1
butyraldehyde	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
nickel sulfate	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
pentanal	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol B	increases expression	1
bisphenol S	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
picoxystrobin	decreases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Acetaminophen	decreases expression	1

Cellosaurus cell lines

2 cell lines: 1 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1ZP	Abcam HeLa OXCT1 KO	Cancer cell line	Female
CVCL_D9LY	Ubigene HEK293 OXCT1 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening