NDUFS2 NADH:ubiquinone oxidoreductase core subunit S2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: NDUFS2provided by HGNC
Official Full Name: NADH:ubiquinone oxidoreductase core subunit S2provided by HGNC
Primary source: HGNC:HGNC:7708
See related: Ensembl:ENSG00000158864 MIM:602985; AllianceGenome:HGNC:7708
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: CI-49; MC1DN6; LHONAR2
Summary: The protein encoded by this gene is a core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (complex I). Mammalian mitochondrial complex I is composed of at least 43 different subunits, 7 of which are encoded by the mitochondrial genome, and the rest are the products of nuclear genes. The iron-sulfur protein fraction of complex I is made up of 7 subunits, including this gene product. Complex I catalyzes the NADH oxidation with concomitant ubiquinone reduction and proton ejection out of the mitochondria. Mutations in this gene are associated with mitochondrial complex I deficiency. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]
Expression: Ubiquitous expression in heart (RPKM 60.3), kidney (RPKM 35.6) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1q23.3

Exon count:: 15

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (161197417..161214395)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (160334507..160351847)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (161167207..161184185)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

NUDT21 interacts with NDUFS2 to activate the PI3K/AKT pathway and promotes pancreatic cancer pathogenesis.
Title: NUDT21 interacts with NDUFS2 to activate the PI3K/AKT pathway and promotes pancreatic cancer pathogenesis.
Complex I protein NDUFS2 is vital for growth, ROS generation, membrane integrity, apoptosis, and mitochondrial energetics.
Title: Complex I protein NDUFS2 is vital for growth, ROS generation, membrane integrity, apoptosis, and mitochondrial energetics.
findings uncover a novel S100A4 function and highlight its importance in controlling NDUFS2 expression to regulate the plasticity of mitochondrial metabolism and thereby promote the invasive and metastatic capacity in lung cancer
Title: S100A4 alters metabolism and promotes invasion of lung cancer cells by up-regulating mitochondrial complex I protein NDUFS2.
compound heterozygosity for severe and hypomorphic NDUFS2 mutations can cause non-syndromic hereditary optic neuropathy.
Title: Compound heterozygosity for severe and hypomorphic NDUFS2 mutations cause non-syndromic LHON-like optic neuropathy.
Results found nominal significant associations of 2 SNPs in the NDUFS1 gene and 4 SNPs in the NDUFS2 gene with early onset schizophrenia (EOS), but none of these associations survived the Bonferroni correction.
Title: Do nuclear-encoded core subunits of mitochondrial complex I confer genetic susceptibility to schizophrenia in Han Chinese populations?
NDUFAF7 methylates arginine 85 in the NDUFS2 subunit of human complex I.
Title: NDUFAF7 methylates arginine 85 in the NDUFS2 subunit of human complex I.
study describes clinical, radiological, biochemical and molecular data of 6 patients with Leigh syndrome with novel mutations in NDUFV1 and NDUFS2; 2 siblings were compound heterozygotes for an undescribed E104A mutation in NDUFS2
Title: Leigh syndrome associated with mitochondrial complex I deficiency due to novel mutations In NDUFV1 and NDUFS2.
The NDUFS2 mutation affects complex I enzymatic function.
Title: A catalytic defect in mitochondrial respiratory chain complex I due to a mutation in NDUFS2 in a patient with Leigh syndrome.
Our results confirm that NDUFS2 is a mutational hotspot in Caucasian children with isolated complex I deficiency and recommend the routine diagnostic investigation of this gene in patients with Leigh or Leigh-like phenotypes.
Title: The p.M292T NDUFS2 mutation causes complex I-deficient Leigh syndrome in multiple families.
Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.

Submit: New GeneRIF Correction See all GeneRIFs (12)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Leber-like hereditary optic neuropathy, autosomal recessive 2 MedGen: C5882713 OMIM: 620569 GeneReviews: Not available	Compare labs
Mitochondrial complex 1 deficiency, nuclear type 6 MedGen: C4748759 OMIM: 618228 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH70304 (e-PCR)
- UniSTS:54328

RH119317 (e-PCR)
- UniSTS:133879

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables 4 iron, 4 sulfur cluster binding	IEA Inferred from Electronic Annotation more info
enables NAD binding	IEA Inferred from Electronic Annotation more info
contributes_to NADH dehydrogenase (ubiquinone) activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables NADH dehydrogenase (ubiquinone) activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables NADH dehydrogenase (ubiquinone) activity	NAS Non-traceable Author Statement more info	PubMed
contributes_to NADH dehydrogenase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables electron transfer activity	NAS Non-traceable Author Statement more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables oxygen sensor activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables quinone binding	IEA Inferred from Electronic Annotation more info
enables ubiquitin protein ligase binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in aerobic respiration	NAS Non-traceable Author Statement more info	PubMed
involved_in cellular response to oxygen levels	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in gliogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in mitochondrial ATP synthesis coupled electron transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mitochondrial electron transport, NADH to ubiquinone	IBA Inferred from Biological aspect of Ancestor more info
involved_in mitochondrial electron transport, NADH to ubiquinone	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mitochondrial electron transport, NADH to ubiquinone	NAS Non-traceable Author Statement more info	PubMed
involved_in mitochondrial respiratory chain complex I assembly	ISS Inferred from Sequence or Structural Similarity more info
involved_in neural precursor cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
involved_in neurogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in proton motive force-driven mitochondrial ATP synthesis	NAS Non-traceable Author Statement more info	PubMed
involved_in proton transmembrane transport	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in mitochondrial inner membrane	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrial matrix	TAS Traceable Author Statement more info
located_in mitochondrion	HTP more info	PubMed
located_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrion	NAS Non-traceable Author Statement more info	PubMed
located_in nucleoplasm	IDA Inferred from Direct Assay more info
part_of respiratory chain complex I	IBA Inferred from Biological aspect of Ancestor more info
part_of respiratory chain complex I	IDA Inferred from Direct Assay more info	PubMed
part_of respiratory chain complex I	IMP Inferred from Mutant Phenotype more info	PubMed
part_of respiratory chain complex I	NAS Non-traceable Author Statement more info	PubMed

General protein information

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Preferred Names: NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial

Names: CI-49kD; NADH dehydrogenase (ubiquinone) Fe-S protein 2, 49kDa (NADH-coenzyme Q reductase); NADH-ubiquinone oxidoreductase 49 kDa subunit; NADH-ubiquinone oxidoreductase NDUFS2 subunit; complex 1, mitochondrial respiratory chain, 49-KD subunit; complex I 49kDa subunit

NP_001159631.1

EC 7.1.1.2

NP_001364227.1

EC 7.1.1.2

NP_001364228.1

EC 7.1.1.2

NP_001364229.1

EC 7.1.1.2

NP_001364230.1

EC 7.1.1.2

NP_001364231.1

EC 7.1.1.2

NP_001397818.1

EC 7.1.1.2

NP_004541.1

EC 7.1.1.2

XP_005245266.1

EC 7.1.1.2

XP_054192732.1

EC 7.1.1.2

XP_054192733.1

EC 7.1.1.2

NCBI Reference Sequences (RefSeq)

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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_013352.1 RefSeqGene

Range

8053..20081

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001166159.2 → NP_001159631.1 NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial isoform 2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs at the 3' end compared to variant 1, resulting in a shorter isoform (2) with a distinct C-terminus compared to isoform 1. Variants 2, 5, 6, and 7 all encode the same isoform (2).

Source sequence(s)

AL590714

Consensus CDS

CCDS53404.1

UniProtKB/TrEMBL

Q53HG2

Related

ENSP00000376018.4, ENST00000392179.5

Conserved Domains (1) summary

PRK06075
Location:77 → 457

PRK06075; NADH-quinone oxidoreductase subunit D
NM_001377298.1 → NP_001364227.1 NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial isoform 1 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (3), as well as variants 1 and 4, encodes isoform 1.

Source sequence(s)

AL590714

Consensus CDS

CCDS1224.1

UniProtKB/Swiss-Prot

D3DVG7, J3KPM7, O75306, Q5VTW0, Q969P3, Q9UEV3

UniProtKB/TrEMBL

Q53HG2

Related

ENSP00000504199.1, ENST00000678507.1

Conserved Domains (1) summary

PRK06075
Location:77 → 463

PRK06075; NADH-quinone oxidoreductase subunit D
NM_001377299.1 → NP_001364228.1 NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial isoform 1 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (4), as well as variants 1 and 3, encodes isoform 1.

Source sequence(s)

AL590714

Consensus CDS

CCDS1224.1

UniProtKB/Swiss-Prot

D3DVG7, J3KPM7, O75306, Q5VTW0, Q969P3, Q9UEV3

UniProtKB/TrEMBL

Q53HG2

Related

ENSP00000503117.1, ENST00000676972.1

Conserved Domains (1) summary

PRK06075
Location:77 → 463

PRK06075; NADH-quinone oxidoreductase subunit D
NM_001377300.1 → NP_001364229.1 NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial isoform 2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (5), as well as variants 2, 6, and 7, encodes isoform 2.

Source sequence(s)

AL590714

Consensus CDS

CCDS53404.1

UniProtKB/TrEMBL

Q53HG2

Related

ENSP00000503353.1, ENST00000677550.1

Conserved Domains (1) summary

PRK06075
Location:77 → 457

PRK06075; NADH-quinone oxidoreductase subunit D
NM_001377301.1 → NP_001364230.1 NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial isoform 2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (6), as well as variants 2, 5, and 7, encodes isoform 2.

Source sequence(s)

AL590714

Consensus CDS

CCDS53404.1

UniProtKB/TrEMBL

Q53HG2

Related

ENSP00000504170.1, ENST00000679176.1

Conserved Domains (1) summary

PRK06075
Location:77 → 457

PRK06075; NADH-quinone oxidoreductase subunit D
NM_001377302.1 → NP_001364231.1 NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial isoform 2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (7), as well as variants 2, 5, and 6, encodes isoform 2.

Source sequence(s)

AL590714

Consensus CDS

CCDS53404.1

UniProtKB/TrEMBL

Q53HG2

Conserved Domains (1) summary

PRK06075
Location:77 → 457

PRK06075; NADH-quinone oxidoreductase subunit D
NM_001410889.1 → NP_001397818.1 NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial isfoform 3

Status: REVIEWED

Source sequence(s)

AL590714

Consensus CDS

CCDS91086.1

UniProtKB/TrEMBL

A0A7I2V4G5

Related

ENSP00000503946.1, ENST00000678911.1
NM_004550.5 → NP_004541.1 NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial isoform 1 precursor

See identical proteins and their annotated locations for NP_004541.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1). Variants 1, 3, and 4 all encode the same isoform (1).

Source sequence(s)

BC000170, BC008868

Consensus CDS

CCDS1224.1

UniProtKB/Swiss-Prot

D3DVG7, J3KPM7, O75306, Q5VTW0, Q969P3, Q9UEV3

UniProtKB/TrEMBL

Q53HG2

Related

ENSP00000356972.3, ENST00000367993.7

Conserved Domains (1) summary

PRK06075
Location:77 → 463

PRK06075; NADH-quinone oxidoreductase subunit D

RNA

NR_165188.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AL590714

Related

ENST00000678880.1

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000001.11 Reference GRCh38.p14 Primary Assembly

Range

161197417..161214395

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005245209.3 → XP_005245266.1 NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial isoform X1

UniProtKB/TrEMBL

B7Z792

Conserved Domains (2) summary

PRK06075
Location:1 → 365

PRK06075; NADH dehydrogenase subunit D; Validated

COG0649
Location:1 → 365

NuoD; NADH:ubiquinone oxidoreductase 49 kD subunit (chain D) [Energy production and conversion]

Alternate T2T-CHM13v2.0

Genomic

NC_060925.1 Alternate T2T-CHM13v2.0

Range

160334507..160351847

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054336757.1 → XP_054192732.1 NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial isoform X2
XM_054336758.1 → XP_054192733.1 NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial isoform X1