SUCLG1 succinate-CoA ligase GDP/ADP-forming subunit alpha [Homo sapiens (human)] - Gene

Summary

Official Symbol: SUCLG1provided by HGNC
Official Full Name: succinate-CoA ligase GDP/ADP-forming subunit alphaprovided by HGNC
Primary source: HGNC:HGNC:11449
See related: Ensembl:ENSG00000163541 MIM:611224; AllianceGenome:HGNC:11449
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: GALPHA; MTDPS9; SUCLA1
Summary: This gene encodes the alpha subunit of the heterodimeric enzyme succinate coenzyme A ligase. This enzyme is targeted to the mitochondria and catalyzes the conversion of succinyl CoA and ADP or GDP to succinate and ATP or GTP. Mutations in this gene are the cause of the metabolic disorder fatal infantile lactic acidosis and mitochondrial DNA depletion. [provided by RefSeq, Feb 2010]
Expression: Broad expression in kidney (RPKM 188.3), duodenum (RPKM 98.6) and 25 other tissues See more
Orthologs: all
: Try the new Gene page
Try the new Transcripts and proteins table

Genomic context

Location:: 2p11.2

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2025_08	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (84423528..84459280, complement)
RS_2025_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (84425228..84460977, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (84650652..84686404, complement)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

SUCLG1 restricts POLRMT succinylation to enhance mitochondrial biogenesis and leukemia progression.
Title: SUCLG1 restricts POLRMT succinylation to enhance mitochondrial biogenesis and leukemia progression.
We report two Tunisian patients belonging to a consanguineous family with mitochondrial encephalomyopathy. Mutational analysis of SUCLG1 gene showed the presence of c.41T > C in exon 1 in a homozygous state. This mutation substitutes a conserved methionine residue to a threonine at position 14 (p.M14T) located at the SUCLG1 protein mitochondrial targeting sequence.
Title: Clinical, Molecular, and Computational Analysis in two cases with mitochondrial encephalomyopathy associated with SUCLG1 mutation in a consanguineous family.
These abnormal phenotypes are rescued upon ectopic expression of wild-type SUCLG1 in the patient's fibroblasts, thus functionally confirming the pathogenic nature of the SUCLG1 VUS identified in this patient and expanding the phenotypic spectrum for SUCLG1 deficiency
Title: Expanding the phenotypic spectrum of Succinyl-CoA ligase deficiency through functional validation of a new SUCLG1 variant.
Long survival, to age 20 years or older, was reported in 12% of SUCLA2 and in 10% of SUCLG1 patients.
Title: Succinate-CoA ligase deficiency due to mutations in SUCLA2 and SUCLG1: phenotype and genotype correlations in 71 patients.
First Chinese report of succinyl-CoA ligase deficiency caused by novel SUCLG1 mutations; five novel pathogenic mutations in SUCLG1 were identified
Title: Five novel SUCLG1 mutations in three Chinese patients with succinate-CoA ligase deficiency noticed by mild methylmalonic aciduria.
3 novel mutations have been identified in patients with the mitochondrial DNA depletion syndrome (c.1048G>A and c.1049G>T in SUCLA2 and c.531+4A>T in SUCLG1).
Title: Mitochondrial DNA depletion syndrome: new descriptions and the use of citrate synthase as a helpful tool to better characterise the patients.
Our results suggest that SUCLG1 mutations that lead to complete absence of SUCLG1 protein are responsible for a very severe disorder with antenatal manifestations, whereas a SUCLA2-like phenotype is found in patients with residual SUCLG1 protein.
Title: The severity of phenotype linked to SUCLG1 mutations could be correlated with residual amount of SUCLG1 protein.
Observational study of gene-disease association. (HuGE Navigator)
Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
This report enlarges the phenotypic spectrum of SUCLG1 mutations and confirms that a characteristic metabolic profile (presence of MMA and C4-DC carnitine in urines) and basal ganglia MRI lesions are the hallmarks of SCS defects.
Title: New SUCLG1 patients expanding the phenotypic spectrum of this rare cause of mild methylmalonic aciduria.
A novel mutation in the SUCLG1 gene was found in two newborns having lethal lactic acidosis, multi-organ failure and congenital malformations including interrupted aortic arch.
Title: Marked mitochondrial DNA depletion associated with a novel SUCLG1 gene mutation resulting in lethal neonatal acidosis, multi-organ failure, and interrupted aortic arch.

Submit: New GeneRIF Correction

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Mitochondrial DNA depletion syndrome 9 MedGen: C3151476 OMIM: 245400 GeneReviews: SUCLG1-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria	Compare labs

EBI GWAS Catalog

Description
Genetics of coronary artery calcification among African Americans, a meta-analysis. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Protein	Gene	Interaction	Pubs
Vpr	vpr	A stable-isotope labeling by amino acids in cell culture coupled with mass spectrometry-based proteomics identifies downregulation of succinate-CoA ligase, alpha subunit (SUCLG1) expression by HIV-1 Vpr in Vpr transduced macrophages	PubMed

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

RH91265 (e-PCR)
- UniSTS:87053

SHGC-35054 (e-PCR)
- UniSTS:28178

D8S2279 (e-PCR)
- UniSTS:473907

WI-15353 (e-PCR)
- UniSTS:81462

D1S1423 (e-PCR)
- UniSTS:149619

RH68703 (e-PCR)
- UniSTS:82099

D11S2875 (e-PCR)
- UniSTS:152053

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables RNA binding	HDA more info	PubMed
contributes_to acid-thiol ligase activity	IDA Inferred from Direct Assay more info	PubMed
enables catalytic activity	IEA Inferred from Electronic Annotation more info
enables ligase activity	IEA Inferred from Electronic Annotation more info
enables malate-CoA ligase activity	IEA Inferred from Electronic Annotation more info
enables nucleotide binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables succinate-CoA ligase (ADP-forming) activity	IBA Inferred from Biological aspect of Ancestor more info
contributes_to succinate-CoA ligase (ADP-forming) activity	IEA Inferred from Electronic Annotation more info
enables succinate-CoA ligase (ADP-forming) activity	IEA Inferred from Electronic Annotation more info
enables succinate-CoA ligase (GDP-forming) activity	IBA Inferred from Biological aspect of Ancestor more info
enables succinate-CoA ligase (GDP-forming) activity	IEA Inferred from Electronic Annotation more info
enables succinate-CoA ligase activity	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
involved_in malate metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in succinyl-CoA catabolic process	NAS Non-traceable Author Statement more info	PubMed
involved_in toxic metabolite repair	IDA Inferred from Direct Assay more info	PubMed
involved_in tricarboxylic acid cycle	IBA Inferred from Biological aspect of Ancestor more info
involved_in tricarboxylic acid cycle	IEA Inferred from Electronic Annotation more info
involved_in tricarboxylic acid cycle	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
part_of catalytic complex	IDA Inferred from Direct Assay more info	PubMed
is_active_in mitochondrial matrix	IEA Inferred from Electronic Annotation more info
located_in mitochondrial matrix	TAS Traceable Author Statement more info
located_in mitochondrion	HTP more info	PubMed
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info
is_active_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrion	IEA Inferred from Electronic Annotation more info
located_in mitochondrion	NAS Non-traceable Author Statement more info	PubMed
located_in mitochondrion	TAS Traceable Author Statement more info	PubMed
part_of succinate-CoA ligase complex (ADP-forming)	IBA Inferred from Biological aspect of Ancestor more info
part_of succinate-CoA ligase complex (GDP-forming)	IEA Inferred from Electronic Annotation more info

General protein information

Go to the top of the page Help

Preferred Names: succinate--CoA ligase [ADP/GDP-forming] subunit alpha, mitochondrial

Names: SCS-alpha; itaconyl--CoA ligase [ADP/GDP-forming] subunit alpha; malyl--CoA ligase [ADP/GDP-forming] subunit alpha; mitochondrial succinate--CoA ligase [ADP/GDP-forming] subunit alpha; succinate-CoA ligase alpha subunit; succinyl-CoA ligase [ADP/GDP-forming] subunit alpha, mitochondrial; succinyl-CoA ligase [GDP-forming] subunit alpha, mitochondrial; succinyl-CoA synthetase subunit alpha

NP_003840.2

EC 6.2.1.4

EC 6.2.1.5

EC 6.2.1.9

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_016755.1 RefSeqGene

Range

5183..40935

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_003849.4 → NP_003840.2 succinate--CoA ligase [ADP/GDP-forming] subunit alpha, mitochondrial precursor

See identical proteins and their annotated locations for NP_003840.2

Status: REVIEWED

Source sequence(s)

AC096770, BC000504, BP194715, BQ774501

Consensus CDS

CCDS1967.2

UniProtKB/Swiss-Prot

P53597, Q9BWB0, Q9UNP6

UniProtKB/TrEMBL

Q6IAL5

Related

ENSP00000377446.2, ENST00000393868.7

Conserved Domains (3) summary

PTZ00187
Location:19 → 344

PTZ00187; succinyl-CoA synthetase alpha subunit; Provisional

pfam02629
Location:53 → 146

CoA_binding; CoA binding domain

cl22543
Location:199 → 324

Ligase_CoA; CoA-ligase