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Aliases for NDUFA4 Gene

Aliases for NDUFA4 Gene

  • NDUFA4, Mitochondrial Complex Associated 2 3 5
  • NADH-Ubiquinone Oxidoreductase MLRQ Subunit 2 3 4
  • NADH Dehydrogenase (Ubiquinone) 1 Alpha Subcomplex, 4, 9kDa 2 3
  • Complex I 9kDa Subunit 2 3
  • Complex I-MLRQ 3 4
  • CI-MLRQ 3 4
  • NADH Dehydrogenase (Ubiquinone) 1 Alpha Subcomplex, 4 (9kD, MLRQ) 2
  • NADH Dehydrogenase [Ubiquinone] 1 Alpha Subcomplex Subunit 4 3
  • Cytochrome C Oxidase Subunit NDUFA4 3
  • CI-9k 3
  • MLRQ 3

External Ids for NDUFA4 Gene

Previous GeneCards Identifiers for NDUFA4 Gene

  • GC07M010617
  • GC07M010717
  • GC07M010746

Summaries for NDUFA4 Gene

Entrez Gene Summary for NDUFA4 Gene

  • The protein encoded by this gene belongs to the complex I 9kDa subunit family. Mammalian complex I of mitochondrial respiratory chain is composed of 45 different subunits. This protein has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. [provided by RefSeq, Jul 2008]

GeneCards Summary for NDUFA4 Gene

NDUFA4 (NDUFA4, Mitochondrial Complex Associated) is a Protein Coding gene. Diseases associated with NDUFA4 include Leigh Syndrome With Leukodystrophy and Leigh Syndrome. Among its related pathways are Gene Expression and Metabolism. Gene Ontology (GO) annotations related to this gene include cytochrome-c oxidase activity. An important paralog of this gene is NDUFA4L2.

UniProtKB/Swiss-Prot for NDUFA4 Gene

  • Cytochrome c oxidase (COX, complex IV) is the terminal component of the mitochondrial respiratory chain that catalyzes the reduction of oxygen to water. Required for complex IV maintenance.

Additional gene information for NDUFA4 Gene

No data available for CIViC summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for NDUFA4 Gene

Genomics for NDUFA4 Gene

GeneHancer (GH) Regulatory Elements for NDUFA4 Gene

Promoters and enhancers for NDUFA4 Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH07J010938 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE 659.5 +0.1 110 3.5 HDGF PKNOX1 FOXA2 SMAD1 ARNT ARID4B SIN3A DMAP1 ZNF2 ZBTB7B NDUFA4 ENSG00000271185 PHF14 GC07M010895
GH07J010972 Promoter/Enhancer 2 EPDnew Ensembl ENCODE 18 -33.6 -33642 2.7 PKNOX1 FOXA2 ARID4B SIN3A DMAP1 YY1 POLR2B E2F8 FOS KLF13 PHF14 NDUFA4 GC07P010991
GH07J011212 Enhancer 0.6 ENCODE 10.8 -273.0 -272964 1.1 CTCF TFAP4 HLF DPF2 FOXA1 ZNF217 NFIL3 CTBP1 GATA3 POLR2A NDUFA4 PHF14 LOC105375153 GC07M011257
GH07J011211 Enhancer 0.6 ENCODE 10.8 -272.0 -272022 0.7 GATAD2A CTCF ZNF654 TRIM22 REST RAD21 TEAD3 ZNF143 SMC3 RCOR1 NDUFA4 PHF14 LOC105375153 GC07M011257
GH07J010998 Enhancer 0.4 ENCODE 10.8 -58.9 -58861 0.5 CREB1 HMBOX1 CREM PHF14 NDUFA4 RPL23AP52 GC07P010991
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around NDUFA4 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the NDUFA4 gene promoter:
  • FOXJ2 (long isoform)
  • FOXJ2
  • CUTL1
  • COUP
  • COUP-TF1
  • HNF-4alpha1
  • HNF-4alpha2
  • LCR-F1
  • GR

Genomic Locations for NDUFA4 Gene

Genomic Locations for NDUFA4 Gene
8,306 bases
Minus strand
8,306 bases
Minus strand

Genomic View for NDUFA4 Gene

Genes around NDUFA4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NDUFA4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NDUFA4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NDUFA4 Gene

Proteins for NDUFA4 Gene

  • Protein details for NDUFA4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Cytochrome c oxidase subunit NDUFA4
    Protein Accession:
    Secondary Accessions:
    • A4D109
    • Q6FHN5

    Protein attributes for NDUFA4 Gene

    81 amino acids
    Molecular mass:
    9370 Da
    Quaternary structure:
    • Component of the cytochrome c oxidase complex (COX, complex IV).
    • During complex IV purifications dissociates from complex IV upon treatment with standard detergent DDM (decyl beta-D-maltoside) in high concentrations (PubMed:22902835, PubMed:23746447).

neXtProt entry for NDUFA4 Gene

Post-translational modifications for NDUFA4 Gene

  • Ubiquitination at Lys75, isoforms=73, isoforms=63, and Lys55
  • Modification sites at PhosphoSitePlus

Other Protein References for NDUFA4 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for NDUFA4 Gene

Domains & Families for NDUFA4 Gene

Gene Families for NDUFA4 Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted membrane proteins

Protein Domains for NDUFA4 Gene


Suggested Antigen Peptide Sequences for NDUFA4 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the complex IV NDUFA4 subunit family.
  • Belongs to the complex IV NDUFA4 subunit family.
genes like me logo Genes that share domains with NDUFA4: view

Function for NDUFA4 Gene

Molecular function for NDUFA4 Gene

UniProtKB/Swiss-Prot Function:
Cytochrome c oxidase (COX, complex IV) is the terminal component of the mitochondrial respiratory chain that catalyzes the reduction of oxygen to water. Required for complex IV maintenance.

Phenotypes From GWAS Catalog for NDUFA4 Gene

Gene Ontology (GO) - Molecular Function for NDUFA4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004129 contributes_to cytochrome-c oxidase activity IMP 22902835
GO:0005515 protein binding IPI 19822128
GO:0008137 NADH dehydrogenase (ubiquinone) activity TAS,NAS 9878551
GO:0044877 protein-containing complex binding IDA 23209302
genes like me logo Genes that share ontologies with NDUFA4: view
genes like me logo Genes that share phenotypes with NDUFA4: view

Human Phenotype Ontology for NDUFA4 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

Clone Products

No data available for Enzyme Numbers (IUBMB) , Animal Models , Transcription Factor Targets and HOMER Transcription for NDUFA4 Gene

Localization for NDUFA4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NDUFA4 Gene

Mitochondrion inner membrane; Peripheral membrane protein; Matrix side.

Subcellular locations from

Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for NDUFA4 gene
Compartment Confidence
extracellular 5
mitochondrion 5
nucleus 1
cytosol 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for NDUFA4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005739 mitochondrion IDA 16729965
GO:0005743 mitochondrial inner membrane TAS --
GO:0005747 mitochondrial respiratory chain complex I NAS 9878551
GO:0005751 mitochondrial respiratory chain complex IV IDA 22902835
GO:0016020 membrane IEA --
genes like me logo Genes that share ontologies with NDUFA4: view

Pathways & Interactions for NDUFA4 Gene

genes like me logo Genes that share pathways with NDUFA4: view

Gene Ontology (GO) - Biological Process for NDUFA4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006120 mitochondrial electron transport, NADH to ubiquinone NAS 9878551
GO:0006123 mitochondrial electron transport, cytochrome c to oxygen TAS --
GO:0055114 oxidation-reduction process IEA --
GO:1902600 proton transmembrane transport IEA --
genes like me logo Genes that share ontologies with NDUFA4: view

No data available for SIGNOR curated interactions for NDUFA4 Gene

Drugs & Compounds for NDUFA4 Gene

(5) Drugs for NDUFA4 Gene - From: DrugBank and HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
NADH Approved Nutra Target 0
FAD Approved Pharma 0
Ubiquinone-1 Experimental Pharma 0
Ubiquinone-2 Experimental Pharma 0
NAD Pharma Full agonist, Agonist, Activator 0

(3) Additional Compounds for NDUFA4 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
  • FE (II) ion
  • Fe(II)
  • Fe(2+)
  • Ferrous ion
  • Iron ion(2+)
  • CoQH2
  • Coenzymes QH2
  • Reduced ubiquinone
  • Ubiquinol
  • Ubiquinone-1
  • S(2-)
  • Sulphide
  • Sulfanediide
  • Sulfur
genes like me logo Genes that share compounds with NDUFA4: view

Transcripts for NDUFA4 Gene

mRNA/cDNA for NDUFA4 Gene

(1) REFSEQ mRNAs :
(10) Additional mRNA sequences :
(953) Selected AceView cDNA sequences:
(6) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for NDUFA4 Gene

NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4, 9kDa:
Representative Sequences:

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for NDUFA4 Gene

No ASD Table

Relevant External Links for NDUFA4 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for NDUFA4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for NDUFA4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for NDUFA4 Gene

This gene is overexpressed in Heart - Left Ventricle (x4.4).

Protein differential expression in normal tissues from HIPED for NDUFA4 Gene

This gene is overexpressed in Nasal epithelium (14.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for NDUFA4 Gene

Protein tissue co-expression partners for NDUFA4 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of NDUFA4 Gene:


SOURCE GeneReport for Unigene cluster for NDUFA4 Gene:


Evidence on tissue expression from TISSUES for NDUFA4 Gene

  • Nervous system(4.9)
  • Liver(4.8)
  • Heart(4.2)
  • Eye(3.5)
  • Lung(2.7)
  • Muscle(2.7)
  • Stomach(2.4)
  • Skin(2.3)

Phenotype-based relationships between genes and organs from Gene ORGANizer for NDUFA4 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
  • cardiovascular
  • digestive
  • integumentary
  • nervous
  • respiratory
  • skeletal muscle
Head and neck:
  • brain
  • cerebellum
  • cerebrospinal fluid
  • cranial nerve
  • eye
  • eyelid
  • face
  • head
  • meninges
  • neck
  • lung
  • liver
  • hair
  • peripheral nervous system
  • skin
  • spinal cord
genes like me logo Genes that share expression patterns with NDUFA4: view

No data available for mRNA Expression by UniProt/SwissProt for NDUFA4 Gene

Orthologs for NDUFA4 Gene

This gene was present in the common ancestor of animals.

Orthologs for NDUFA4 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia NDUFA4 34 33
  • 100 (n)
(Canis familiaris)
Mammalia NDUFA4 33
  • 90.12 (n)
-- 34
  • 87 (a)
-- 34
  • 77 (a)
(Bos Taurus)
Mammalia NDUFA4 34 33
  • 89.3 (n)
(Mus musculus)
Mammalia Ndufa4 16 34 33
  • 86.42 (n)
(Rattus norvegicus)
Mammalia Ndufa4 33
  • 85.6 (n)
(Monodelphis domestica)
Mammalia NDUFA4 34
  • 82 (a)
(Gallus gallus)
Aves NDUFA4 34 33
  • 76.13 (n)
tropical clawed frog
(Silurana tropicalis)
Amphibia ndufa4 33
  • 65.02 (n)
African clawed frog
(Xenopus laevis)
Amphibia Xl.23855 33
(Danio rerio)
Actinopterygii ndufa4 34 33
  • 64.61 (n)
fruit fly
(Drosophila melanogaster)
Insecta CG32230 34
  • 51 (a)
Species where no ortholog for NDUFA4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • lizard (Anolis carolinensis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for NDUFA4 Gene

Gene Tree for NDUFA4 (if available)
Gene Tree for NDUFA4 (if available)
Evolutionary constrained regions (ECRs) for NDUFA4: view image

Paralogs for NDUFA4 Gene

Variants for NDUFA4 Gene

Sequence variations from dbSNP and Humsavar for NDUFA4 Gene

SNP ID Clin Chr 07 pos Variation AA Info Type
rs1057523221 likely-benign, not specified 10,940,063(-) C/T 5_prime_UTR_variant
rs115234096 likely-benign, not specified 10,940,064(-) G/A/T 5_prime_UTR_variant
rs17163797 benign, not specified 10,940,070(-) G/A 5_prime_UTR_variant
rs587776505 not-provided, not provided 10,938,862(-) G/A coding_sequence_variant, missense_variant
rs1000523474 -- 10,934,471(-) C/T intron_variant

Structural Variations from Database of Genomic Variants (DGV) for NDUFA4 Gene

Variant ID Type Subtype PubMed ID
esv2752140 CNV gain 17911159
esv3891050 CNV gain 25118596
esv3891051 CNV loss 25118596
nsv1017291 CNV loss 25217958
nsv1019888 CNV gain 25217958
nsv1027289 CNV loss 25217958
nsv1029882 CNV loss 25217958
nsv1161498 CNV deletion 26073780
nsv464364 CNV loss 19166990
nsv606187 CNV gain 21841781
nsv606193 CNV loss 21841781
nsv970794 CNV duplication 23825009

Variation tolerance for NDUFA4 Gene

Residual Variation Intolerance Score: 57% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.25; 5.67% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for NDUFA4 Gene

Human Gene Mutation Database (HGMD)
SNPedia medical, phenotypic, and genealogical associations of SNPs for

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NDUFA4 Gene

Disorders for NDUFA4 Gene

MalaCards: The human disease database

(2) MalaCards diseases for NDUFA4 Gene - From: Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
leigh syndrome with leukodystrophy
  • infantile subacute necrotizing encephalopathy with leukodystrophy
leigh syndrome
  • ls
- elite association - COSMIC cancer census association via MalaCards


  • Leigh syndrome (LS) [MIM:256000]: An early-onset progressive neurodegenerative disorder characterized by the presence of focal, bilateral lesions in one or more areas of the central nervous system including the brainstem, thalamus, basal ganglia, cerebellum and spinal cord. Clinical features depend on which areas of the central nervous system are involved and include subacute onset of psychomotor retardation, hypotonia, ataxia, weakness, vision loss, eye movement abnormalities, seizures, and dysphagia. {ECO:0000269 PubMed:23746447}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for NDUFA4

Genetic Association Database
Human Genome Epidemiology Navigator
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with NDUFA4: view

No data available for Genatlas for NDUFA4 Gene

Publications for NDUFA4 Gene

  1. NDUFA4 is a subunit of complex IV of the mammalian electron transport chain. (PMID: 22902835) Balsa E … Enríquez JA (Cell metabolism 2012) 2 3 4 58
  2. Cloning of the human cDNA sequence encoding the NADH:ubiquinone oxidoreductase MLRQ subunit. (PMID: 9352085) Kim JW … Choe IS (Biochemistry and molecular biology international 1997) 2 3 4 58
  3. NDUFA4 mutations underlie dysfunction of a cytochrome c oxidase subunit linked to human neurological disease. (PMID: 23746447) Pitceathly RD … UK10K Consortium (Cell reports 2013) 3 4 58
  4. Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression. (PMID: 20877624) Hendrickson SL … O'Brien SJ (PloS one 2010) 3 44 58
  5. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4 58

Products for NDUFA4 Gene

Sources for NDUFA4 Gene

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