succinyl-CoA:3-ketoacid CoA transferase deficiency

Summary

succinyl-CoA:3-ketoacid CoA transferase deficiency (MONDO:0009492) is a disease caused by OXCT1 (GenCC Definitive), with 2 cohort genes and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: OXCT1 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 201
• Phenotypes (HPO): 14
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		32	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

14 HPO clinical features (Orphanet curated; top 14 by frequency):

HPO ID	Term	Frequency
HP:0001993	Ketoacidosis	Very frequent (80-99%)
HP:6000361	Reduced succinyl-CoA:3-oxoacid-CoA transferase activity in cultured fibroblasts	Very frequent (80-99%)
HP:0002013	Vomiting	Frequent (30-79%)
HP:0002789	Tachypnea	Frequent (30-79%)
HP:0002919	Ketonuria	Frequent (30-79%)
HP:0410175	Hyperketonemia	Frequent (30-79%)
HP:0001252	Hypotonia	Occasional (5-29%)
HP:0001254	Lethargy	Occasional (5-29%)
HP:0001259	Coma	Occasional (5-29%)
HP:0001531	Failure to thrive in infancy	Occasional (5-29%)
HP:0001640	Cardiomegaly	Occasional (5-29%)
HP:0001944	Dehydration	Occasional (5-29%)
HP:0002018	Nausea	Occasional (5-29%)
HP:0004325	Decreased body weight	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	succinyl-CoA:3-ketoacid CoA transferase deficiency
Mondo ID	MONDO:0009492
MeSH	C537527
OMIM	245050
Orphanet	832
SNOMED CT	238004006
UMLS	C0342792
MedGen	137979
GARD	0004774
Is cancer (heuristic)	no

Also known as: 3-oxoacid CoA transferase deficiency · OXCT1 deficiency · SCOT deficiency · SCOTD · Succinyl CoA:3-oxoacid CoA transferase deficiency · succinyl-CoA acetoacetate transferase deficiency · succinyl-CoA:3-ketoacid CoA transferase deficiency · succinyl-CoA:3-oxoacid CoA transferase deficiency · succinyl-CoA:3-oxoacid-CoA transferase deficiency

Data availability: 201 ClinVar variants · 6 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inherited lipid metabolism disorder › inborn disorder of ketolysis › succinyl-CoA:3-ketoacid CoA transferase deficiency

Related subtypes (1): beta-ketothiolase deficiency

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

201 retrieved; paginated sample, class counts are floors:

75 uncertain significance, 67 likely benign, 23 benign, 11 likely pathogenic, 10 pathogenic, 7 benign/likely benign, 7 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
8165	NM_000436.3(OXCT1):c.[173C>T;398T>A]		Pathogenic	no assertion criteria provided
1064695	NM_000436.4(OXCT1):c.1370C>T (p.Thr457Ile)	OXCT1	Pathogenic	no assertion criteria provided
1071420	NM_000436.4(OXCT1):c.803G>A (p.Arg268His)	OXCT1	Pathogenic	criteria provided, single submitter
1071421	NM_000436.4(OXCT1):c.649C>T (p.Arg217Ter)	OXCT1	Pathogenic	criteria provided, single submitter
1686001	NM_000436.4(OXCT1):c.733-2A>G	OXCT1	Pathogenic	criteria provided, single submitter
1705309	NM_000436.4(OXCT1):c.1419+1G>C	OXCT1	Pathogenic	criteria provided, single submitter
2115740	NM_000436.4(OXCT1):c.873dup (p.Ala292fs)	OXCT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
8163	NM_000436.4(OXCT1):c.848C>G (p.Ser283Ter)	OXCT1	Pathogenic	no assertion criteria provided
8164	NM_000436.4(OXCT1):c.1367G>T (p.Cys456Phe)	OXCT1	Pathogenic	no assertion criteria provided
8166	NM_000436.4(OXCT1):c.971G>A (p.Gly324Glu)	OXCT1	Pathogenic	criteria provided, single submitter
8167	NM_000436.4(OXCT1):c.656G>A (p.Gly219Glu)	OXCT1	Pathogenic	no assertion criteria provided
1324840	NM_000436.4(OXCT1):c.278+1G>A	OXCT1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1324841	NM_000436.4(OXCT1):c.450dup (p.Gly151fs)	OXCT1	Likely pathogenic	criteria provided, single submitter
3062096	NM_000436.4(OXCT1):c.1456_1457del (p.Leu486fs)	OXCT1	Likely pathogenic	criteria provided, single submitter
3384092	NM_000436.4(OXCT1):c.1286dup (p.Leu429fs)	OXCT1	Likely pathogenic	criteria provided, single submitter
353659	NM_000436.4(OXCT1):c.1099+2T>C	OXCT1	Likely pathogenic	criteria provided, single submitter
41497	NM_000436.4(OXCT1):c.1248+5G>A	OXCT1	Likely pathogenic	criteria provided, single submitter
631482	NM_000436.4(OXCT1):c.424G>C (p.Ala142Pro)	OXCT1	Likely pathogenic	no assertion criteria provided
800772	NM_000436.4(OXCT1):c.1402C>T (p.Arg468Cys)	OXCT1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
802120	NM_000436.4(OXCT1):c.193G>A (p.Gly65Arg)	OXCT1	Likely pathogenic	criteria provided, single submitter
828111	NM_000436.4(OXCT1):c.370C>T (p.Arg124Ter)	OXCT1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
973561	NM_000436.4(OXCT1):c.1339-2A>G	OXCT1	Likely pathogenic	criteria provided, single submitter
353658	NM_000436.4(OXCT1):c.1339-12T>C	OXCT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
353660	NM_000436.4(OXCT1):c.1080T>C (p.Asp360=)	OXCT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
353661	NM_000436.4(OXCT1):c.956-15A>G	OXCT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
353665	NM_000436.4(OXCT1):c.565-13C>T	OXCT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
714583	NM_000436.4(OXCT1):c.650G>T (p.Arg217Leu)	OXCT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
727754	NM_000436.4(OXCT1):c.477A>G (p.Thr159=)	OXCT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
93003	NM_000436.4(OXCT1):c.1491C>T (p.Asp497=)	OXCT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1514180	NM_000436.4(OXCT1):c.1115C>T (p.Thr372Ile)	LOC121725203	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
OXCT1	Definitive	Autosomal recessive	succinyl-CoA:3-ketoacid CoA transferase deficiency	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
OXCT1	Orphanet:832	Succinyl-CoA:3-oxoacid CoA transferase deficiency

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
OXCT1	HGNC:8527	ENSG00000083720	P55809	Succinyl-CoA:3-ketoacid coenzyme A transferase 1, mitochondrial	gencc,clinvar
OXCT1-AS1	HGNC:40423	ENSG00000248668		OXCT1 antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
OXCT1	Succinyl-CoA:3-ketoacid coenzyme A transferase 1, mitochondrial	Key enzyme for ketone body catabolism.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
OXCT1	Enzyme (other)	yes	2.8.3.5	CoA_transf_BS, CoA_transf_AS, CoA_trans_fam_I
OXCT1-AS1	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
endothelial cell	1
heart right ventricle	1
left ventricle myocardium	1
heart left ventricle	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
OXCT1	294	ubiquitous	marker	left ventricle myocardium, heart right ventricle, endothelial cell
OXCT1-AS1	129		yes	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, heart left ventricle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
OXCT1	1,691
OXCT1-AS1	0

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
OXCT1	P55809	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. Enrichment computed across 2 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Utilization of Ketone Bodies	1	2855.0×	0.002	OXCT1
Ketone body metabolism	1	1903.3×	0.002	OXCT1
Mitochondrial protein degradation	1	114.2×	0.018	OXCT1
Metabolism of lipids	1	31.6×	0.048	OXCT1
Metabolism of proteins	1	12.4×	0.086	OXCT1
Metabolism	1	11.6×	0.086	OXCT1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
ketone catabolic process	1	16852.0×	7e-04	OXCT1
obsolete ketone body metabolic process	1	5617.3×	9e-04	OXCT1
ketone body catabolic process	1	4213.0×	9e-04	OXCT1
response to starvation	1	468.1×	0.005	OXCT1
response to hormone	1	432.1×	0.005	OXCT1
adipose tissue development	1	401.2×	0.005	OXCT1
positive regulation of insulin secretion involved in cellular response to glucose stimulus	1	374.5×	0.005	OXCT1
response to activity	1	324.1×	0.005	OXCT1
response to nutrient	1	295.6×	0.005	OXCT1
response to ethanol	1	146.5×	0.008	OXCT1
heart development	1	78.8×	0.014	OXCT1
response to xenobiotic stimulus	1	69.1×	0.014	OXCT1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
OXCT1	0	0
OXCT1-AS1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
OXCT1	2.8.3.5	3-oxoacid CoA-transferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	OXCT1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	OXCT1-AS1

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
OXCT1	0	—
OXCT1-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

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