NDUFS4 NADH:ubiquinone oxidoreductase subunit S4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: NDUFS4provided by HGNC
Official Full Name: NADH:ubiquinone oxidoreductase subunit S4provided by HGNC
Primary source: HGNC:HGNC:7711
See related: Ensembl:ENSG00000164258 MIM:602694; AllianceGenome:HGNC:7711
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: AQDQ; CI-18; MC1DN1; CI-AQDQ; CI-18 kDa
Summary: This gene encodes an nuclear-encoded accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (complex I, or NADH:ubiquinone oxidoreductase). Complex I removes electrons from NADH and passes them to the electron acceptor ubiquinone. Mutations in this gene can cause mitochondrial complex I deficiencies such as Leigh syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]
Expression: Ubiquitous expression in heart (RPKM 25.7), fat (RPKM 23.7) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 5q11.2

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	5	NC_000005.10 (53560639..53683338)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	5	NC_060929.1 (54388486..54511162)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	5	NC_000005.9 (52856469..52979168)

Chromosome 5 - NC_000005.10 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
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?

Direct neuronal reprogramming of NDUFS4 patient cells identifies the unfolded protein response as a novel general reprogramming hurdle.
Title: Direct neuronal reprogramming of NDUFS4 patient cells identifies the unfolded protein response as a novel general reprogramming hurdle.
Ndufs4 knockout mouse models of Leigh syndrome: pathophysiology and intervention.
Title: Ndufs4 knockout mouse models of Leigh syndrome: pathophysiology and intervention.
Uniparental isodisomy as a cause of mitochondrial complex I respiratory chain disorder due to a novel splicing NDUFS4 mutation.
Title: Uniparental isodisomy as a cause of mitochondrial complex I respiratory chain disorder due to a novel splicing NDUFS4 mutation.
NDUFS4 deletion triggers loss of NDUFA12 in Ndufs4(-/-) mice and Leigh syndrome patients: A stabilizing role for NDUFAF2.
Title: NDUFS4 deletion triggers loss of NDUFA12 in Ndufs4(-/-) mice and Leigh syndrome patients: A stabilizing role for NDUFAF2.
BAP31 interacts with mitochondria-localized proteins, including Tom40, to stimulate the translocation of NDUFS4, the component of complex I from the cytosol to the mitochondria.
Title: BAP31 regulates mitochondrial function via interaction with Tom40 within ER-mitochondria contact sites.
The clinical presentations of five individuals of Hutterite descent with Leigh disease are described herein. An identity-by-descent mapping and candidate gene approach was used to identify a novel homozygous c.393dupA frameshift mutation in the NADH dehydrogenase (ubiquinone) Fe-S protein 4 (NDUFS4) gene.
Title: A novel NDUFS4 frameshift mutation causes Leigh disease in the Hutterite population.
The authors concluded that NDUFS4-related Leigh syndrome is invariably linked to an early onset severe phenotype that results in early death.
Title: Ndufs4 related Leigh syndrome: A case report and review of the literature.
The c.462delA deletion led to a complete lack of NDUFS4 peptide in isolated mitochondria, and this deficiency caused an inefficient mitochondrial complex I assembly and Leigh syndrome symptoms.
Title: Functional characterization of the c.462delA mutation in the NDUFS4 subunit gene of mitochondrial complex I.
Mutations in the NDUFS4 gene and its subunits are associated with the mitochondrial complex I deficiency. (Review)
Title: Cellular and animal models for mitochondrial complex I deficiency: a focus on the NDUFS4 subunit.
Elevated expression of CO I and ND4 were associated with gastric tumorigenesis and tumor dedifferentiation
Title: Altered expression of mitochondrial cytochrome c oxidase I and NADH dehydrogenase 4 transcripts associated with gastric tumorigenesis and tumor dedifferentiation.

Submit: New GeneRIF Correction See all GeneRIFs (23)

Phenotypes

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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 complex I deficiency, nuclear type 1 MedGen: CN257533 OMIM: 252010 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Genome-wide association study identifies three novel susceptibility loci for severe Acne vulgaris. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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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

D5S1732 (e-PCR)
- UniSTS:16013

STS-H45672 (e-PCR)
- UniSTS:43733

SHGC-100364 (e-PCR)
- UniSTS:183806

SHGC-100842 (e-PCR)
- UniSTS:183807

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
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 protein 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 brain development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular respiration	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	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of fibroblast proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in proton motive force-driven mitochondrial ATP synthesis	NAS Non-traceable Author Statement more info	PubMed
involved_in reactive oxygen species metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of protein phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to cAMP	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in 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 inner membrane	TAS Traceable Author Statement more info
part_of mitochondrial respiratory chain complex I	IBA Inferred from Biological aspect of Ancestor more info
part_of mitochondrial respiratory chain complex I	IDA Inferred from Direct Assay more info	PubMed
part_of mitochondrial respiratory chain complex I	IMP Inferred from Mutant Phenotype more info	PubMed
part_of mitochondrial respiratory chain complex I	IPI Inferred from Physical Interaction more info	PubMed
located_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial

Names: NADH dehydrogenase (ubiquinone) Fe-S protein 4, 18kDa (NADH-coenzyme Q reductase); NADH-ubiquinone oxidoreductase 18 kDa subunit; complex I 18kDa subunit; complex I-AQDQ; mitochondrial respiratory chain complex I (18-KD subunit)

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_008200.1 RefSeqGene

Range

5005..127704

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001318051.2 → NP_001304980.1 NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial isoform 2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (5) lacks an alternate exon, which results in a frameshift compared to variant 1. The encoded isoform (2) has a distinct, shorter C-terminus than isoform 1.

Source sequence(s)

BU145342, BU954271, CD692133

UniProtKB/TrEMBL

H0Y9M8

Related

ENSP00000424570.1, ENST00000506765.1

Conserved Domains (1) summary

pfam04800
Location:76 → 117

ETC_C1_NDUFA4; ETC complex I subunit conserved region
NM_002495.4 → NP_002486.1 NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial isoform 1 precursor

See identical proteins and their annotated locations for NP_002486.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1).

Source sequence(s)

AI001139, BU954271, CD692133

Consensus CDS

CCDS3960.1

UniProtKB/Swiss-Prot

O43181, Q9BS69

UniProtKB/TrEMBL

A0A0S2Z433

Related

ENSP00000296684.5, ENST00000296684.10

Conserved Domains (1) summary

pfam04800
Location:76 → 170

ETC_C1_NDUFA4; ETC complex I subunit conserved region

RNA

NR_134473.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (2) contains an alternate internal exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AI001139, BU954271, CD692133, KU178227

Related

ENST00000506974.5
NR_134474.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (3) contains an alternate internal exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AI001139, BU954271, DA609203
NR_134475.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (4) contains an alternate internal exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AI001139, BU954271, CD692133

Related

ENST00000507026.5