SUGCT

protein-coding

succinyl-CoA:glutarate-CoA transferase

Gene summary

This gene encodes a protein that is similar to members of the CaiB/baiF CoA-transferase protein family. Mutations in this gene are associated with glutaric aciduria type III. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jul 2010]

Previous symbols:

C7orf10

MANE transcript

NM_001193313.2

Inheritance

ClinVar variants

P:6U:85B:36

Top phenotype

Glutaric aciduria III

gnomAD constraint

pLI —, LoF o/e 0.69

Max pathogenic AF

—

Genomic locus

chr7:40,135,005-40,860,763

External References & Databases

Ensembl (ENSG00000175600)

Transcript & Mutation Effects

hg38 • Region Span ~725.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

glutaric acidemia type 3SUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009283

Submitter: Orphanet

glutaric acidemia type 3MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0009283

Submitter: PanelApp Australia

glutaric acidemia type 3MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0009283

Submitter: Ambry Genetics

glutaric acidemia type 3MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0009283

Submitter: ClinGen

*SUGCT* was first reported in relation to autosomal recessive glutaric acidemia type 3 in 2008 (Sherman EA, et al., 2008, PMID: 18926513). SUGCT catalyzes the succinyl-CoA-dependent conversion of glutaric acid into glutaryl-CoA preventing urinary loss of the organic acid; in patients with deficiency of SUGCT there is a consequent accumulation of glutaric acid. Glutaric aciduria type 3 is a biochemical phenotype with uncertain clinical relevance. Evidence supporting the relationship between *SUGCT* and glutaric acidemia type 3 includes case-level data and experimental data. Variants in this gene have been reported in at least 12 probands in 6 publications (PMIDs: 18926513, 28766179, 29421601, 2779420, 37920852, 39101156). At least 7 unique missense, nonsense, and frameshift variants have been reported in humans. This gene-disease relationship is supported by the biochemical function of *SUGCT* which is consistent with the biochemical abnormalities observed in individuals with glutaric acidemia type 3 (PMID: 23893049) and the biochemical features of a Sugct knockout mouse (PMID: 31722069). In summary, there is moderate evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged. This gene-disease pair was previously evaluated by the Aminoacidopathy GCEP on 09/25/2020. It was reevaluated on 10/14/2022 and 12/10/2024 which identified three additional cases (PMIDs: 37920852, 39101156). As a result of this reevaluation, the classification remained Moderate.

glutaric acidemia type 3STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009283

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Glutaric aciduria IIIAR

Manifestation: Biochemical

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Comments: The clinical significance of the condition is unclear

Refs: 1909402; 12555941; 18926513

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SUGCT variants in ClinVar

5 Conditions Cataloged

not providedTotal: 96

not specifiedTotal: 67

Glutaryl-CoA oxidase deficiencyTotal: 12

SUGCT-related disorderTotal: 4

C7ORF10 & SUGCT-related disordersTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001193313.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				25 clinvar	2 clinvar	27
missense			79 clinvar	9 clinvar		88
nonsense	1 clinvar	3 clinvar	3 clinvar			7
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)		2 clinvar	1 clinvar			3
Total	1	5	85	34	2	127

Highest pathogenic variant AF is 0.00022272885

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 39 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001193313.2	RefSeq	NP_001180242.2	14	MANE Select
ENST00000335693.9	Ensembl	ENSP00000338475.5	14	MANE Select
NM_001193311.2	RefSeq	NP_001180240.2	15	Standard
NM_001193312.2	RefSeq	NP_001180241.2	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Molecular Function

protein binding
succinate-hydroxymethylglutarate CoA-transferase activity

Cellular Component

mitochondrion

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000309930
Coding exons: 15
Length: 725788
Individuals with no LoFs: 124469
Homozygous LoFs: 0
Heterozygous LoFs: 177
Defined: 124646
p: 0.000710

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.536	225	249	0.904	0.0000126	3014
Missense (PolyPhen)		105	96.978	1.0827		1134
Synonymous	-0.0266	95	94.7	1.00	0.00000532	921
Loss of Function	1.44	17	24.7	0.688	0.00000129	318

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0010	0.0010	notable
Latino/Admixed American	0.00042	0.00041	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.0025	0.0025	notable
Finnish	0.00085	0.00084	rare
European (Non-Finnish)	0.00046	0.00045	rare
South Asian	0.00099	0.00088	rare
Other	0.00086	0.00083	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalyzes the succinyl-CoA-dependent conversion of glutarate to glutaryl-CoA. Can use different dicarboxylic acids as CoA acceptors, the preferred ones are glutarate, succinate, adipate, and 3-hydroxymethylglutarate. {ECO:0000269|PubMed:23893049}.;

Recessive Scores

pRec: 0.171

Intolerance Scores

RVIS EVS: 0.02
RVIS percentile EVS: 55.45

Essentials

Essential (gene trap): N

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium