NADH:ubiquinone oxidoreductase (complex I) catalyzes the transfer of electrons from NADH to ubiquinone (coenzyme Q) in the first step of the mitochondrial respiratory chain, resulting in the translocation of protons across the inner mitochondrial membrane. This gene encodes a complex I assembly factor. Mutations in this gene are a cause of mitochondrial complex I deficiency. [p... See more...

Aliases for NDUFAF4 Gene

Aliases for NDUFAF4 Gene

  • NADH:Ubiquinone Oxidoreductase Complex Assembly Factor 4 2 3 5
  • NADH Dehydrogenase (Ubiquinone) 1 Alpha Subcomplex, Assembly Factor 4 2 3
  • NADH Dehydrogenase [Ubiquinone] 1 Alpha Subcomplex Assembly Factor 4 3 4
  • Hormone-Regulated Proliferation-Associated Protein Of 20 KDa 3 4
  • NADH Dehydrogenase (Ubiquinone) Complex I, Assembly Factor 4 2 3
  • C6orf66 3 4
  • HRPAP20 3 4
  • Hormone-Regulated Proliferation-Associated Protein, 20 KDa 3
  • Chromosome 6 Open Reading Frame 66 2
  • BA22L21.1 3
  • HSPC125 3
  • MC1DN15 3
  • My013 3

External Ids for NDUFAF4 Gene

Previous HGNC Symbols for NDUFAF4 Gene

  • C6orf66

Previous GeneCards Identifiers for NDUFAF4 Gene

  • GC06M097446
  • GC06M097337
  • GC06M094771

Summaries for NDUFAF4 Gene

Entrez Gene Summary for NDUFAF4 Gene

  • NADH:ubiquinone oxidoreductase (complex I) catalyzes the transfer of electrons from NADH to ubiquinone (coenzyme Q) in the first step of the mitochondrial respiratory chain, resulting in the translocation of protons across the inner mitochondrial membrane. This gene encodes a complex I assembly factor. Mutations in this gene are a cause of mitochondrial complex I deficiency. [provided by RefSeq, Oct 2009]

GeneCards Summary for NDUFAF4 Gene

NDUFAF4 (NADH:Ubiquinone Oxidoreductase Complex Assembly Factor 4) is a Protein Coding gene. Diseases associated with NDUFAF4 include Mitochondrial Complex I Deficiency, Nuclear Type 15 and Mitochondrial Complex I Deficiency, Nuclear Type 1. Among its related pathways are Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. and Metabolism. Gene Ontology (GO) annotations related to this gene include calmodulin binding.

UniProtKB/Swiss-Prot Summary for NDUFAF4 Gene

  • Involved in the assembly of mitochondrial NADH:ubiquinone oxidoreductase complex (complex I) (PubMed:18179882, PubMed:28853723). May be involved in cell proliferation and survival of hormone-dependent tumor cells. May be a regulator of breast tumor cell invasion.

Additional gene information for NDUFAF4 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for NDUFAF4 Gene

Genomics for NDUFAF4 Gene

GeneHancer (GH) Regulatory Elements for NDUFAF4 Gene

Promoters and enhancers for NDUFAF4 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH06J096896 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 524.7 +0.1 90 3.2 ZNF217 CTCF TCF12 NRF1 MYC USF1 POLR2G SP1 PHF8 ZFX NDUFAF4 KLHL32 lnc-GPR63-6 GPR63 lnc-KLHL32-6
GH06J096895 Promoter 0.6 Ensembl 523.8 +2.0 1990 0.2 CEBPB SPI1 RBFOX2 CEBPA NDUFAF4 lnc-GPR63-6 lnc-KLHL32-6
GH06J096836 Promoter/Enhancer 1.9 EPDnew Ensembl ENCODE CraniofacialAtlas 35.1 +61.0 60990 2.6 ZSCAN5C ZIC2 POLR2A ZBTB10 ZBTB26 KLF7 TOE1 CTBP1 EZH2 MXI1 GPR63 lnc-NDUFAF4-2 NDUFAF4 piR-37508
GH06J096885 Enhancer 0.5 Ensembl 24.5 +12.4 12390 0.6 NFYB ZNF384 CEBPG IRF1 EBF1 ATF4 CEBPB ATF7 ATF3 ZNF770 NDUFAF4 GPR63 lnc-KLHL32-6 piR-36588-381
GH06J096801 Enhancer 0.4 dbSUPER 33.7 +95.1 95110 2.4 NFE2 MAFG MNT GPR63 NDUFAF4 piR-37508 lnc-NDUFAF4-2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around NDUFAF4 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for NDUFAF4

Top Transcription factor binding sites by QIAGEN in the NDUFAF4 gene promoter:
  • AREB6
  • Bach1
  • POU2F1
  • POU2F1a
  • POU2F1b
  • POU2F1c
  • POU3F2 (N-Oct-5a)
  • POU3F2 (N-Oct-5b)

Genomic Locations for NDUFAF4 Gene

Genomic Locations for NDUFAF4 Gene
chr6:96,889,311-96,897,891
(GRCh38/hg38)
Size:
8,581 bases
Orientation:
Minus strand
chr6:97,337,187-97,345,767
(GRCh37/hg19)
Size:
8,581 bases
Orientation:
Minus strand

Genomic View for NDUFAF4 Gene

Genes around NDUFAF4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NDUFAF4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NDUFAF4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NDUFAF4 Gene

Proteins for NDUFAF4 Gene

  • Protein details for NDUFAF4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9P032-NDUF4_HUMAN
    Recommended name:
    NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 4
    Protein Accession:
    Q9P032
    Secondary Accessions:
    • B2R4J5

    Protein attributes for NDUFAF4 Gene

    Size:
    175 amino acids
    Molecular mass:
    20266 Da
    Quaternary structure:
    • Binds calmodulin. Interacts with NDUFAF3.

neXtProt entry for NDUFAF4 Gene

Post-translational modifications for NDUFAF4 Gene

  • Phosphorylated on serine. Prolactin stimulate serine phosphorylation (By similarity).
  • Ubiquitination at Lys51, Lys60, Lys66, Lys91, Lys97, and Lys107
  • Modification sites at PhosphoSitePlus

Other Protein References for NDUFAF4 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for NDUFAF4 Gene

Domains & Families for NDUFAF4 Gene

Gene Families for NDUFAF4 Gene

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

Protein Domains for NDUFAF4 Gene

Blocks:
  • Protein of unknown function UPF0240
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for NDUFAF4 Gene

GenScript: Design optimal peptide antigens:
  • Hormone-regulated proliferation-associated protein of 20 kDa (NDUF4_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9P032

UniProtKB/Swiss-Prot:

NDUF4_HUMAN :
  • Belongs to the NDUFAF4 family.
Family:
  • Belongs to the NDUFAF4 family.
genes like me logo Genes that share domains with NDUFAF4: view

Function for NDUFAF4 Gene

Molecular function for NDUFAF4 Gene

UniProtKB/Swiss-Prot Function:
Involved in the assembly of mitochondrial NADH:ubiquinone oxidoreductase complex (complex I) (PubMed:18179882, PubMed:28853723). May be involved in cell proliferation and survival of hormone-dependent tumor cells. May be a regulator of breast tumor cell invasion.
UniProtKB/Swiss-Prot Induction:
Expression is low in quiescent cells and is induced in exponentially proliferating cultures. Expression is also induced when prolactin is added to stationary cells. Induced by dietary differentiating agents such as butyrate and retinoic acid.

Phenotypes From GWAS Catalog for NDUFAF4 Gene

Gene Ontology (GO) - Molecular Function for NDUFAF4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 19463981
GO:0005516 calmodulin binding IEA --
genes like me logo Genes that share ontologies with NDUFAF4: view
genes like me logo Genes that share phenotypes with NDUFAF4: view

Human Phenotype Ontology for NDUFAF4 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

CRISPR Products

miRNA for NDUFAF4 Gene

miRTarBase miRNAs that target NDUFAF4

Clone Products

No data available for Enzyme Numbers (IUBMB) , Animal Models , Transcription Factor Targets and HOMER Transcription for NDUFAF4 Gene

Localization for NDUFAF4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NDUFAF4 Gene

Mitochondrion. Membrane; Lipid-anchor.

Subcellular locations from

COMPARTMENTS
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 NDUFAF4 gene
Compartment Confidence
mitochondrion 5
cytosol 3
nucleus 2
cytoskeleton 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for NDUFAF4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005739 mitochondrion IDA,IBA 18179882
GO:0005743 mitochondrial inner membrane TAS --
GO:0016020 membrane IEA --
GO:0031966 mitochondrial membrane IDA 19463981
genes like me logo Genes that share ontologies with NDUFAF4: view

Pathways & Interactions for NDUFAF4 Gene

genes like me logo Genes that share pathways with NDUFAF4: view

Gene Ontology (GO) - Biological Process for NDUFAF4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0010257 NADH dehydrogenase complex assembly IEA --
GO:0032981 mitochondrial respiratory chain complex I assembly TAS --
genes like me logo Genes that share ontologies with NDUFAF4: view

No data available for SIGNOR curated interactions for NDUFAF4 Gene

Drugs & Compounds for NDUFAF4 Gene

(1) Drugs for NDUFAF4 Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
NADH Approved Nutra 0
genes like me logo Genes that share compounds with NDUFAF4: view

Transcripts for NDUFAF4 Gene

mRNA/cDNA for NDUFAF4 Gene

1 REFSEQ mRNAs :
9 NCBI additional mRNA sequence :
3 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for NDUFAF4 Gene

ExUns: 1a · 1b · 1c ^ 2 ^ 3a · 3b ^ 4 ^ 5a · 5b · 5c · 5d
SP1: - - -
SP2: - - - -
SP3: - - -
SP4: - -
SP5: -

Relevant External Links for NDUFAF4 Gene

GeneLoc Exon Structure for
NDUFAF4

Expression for NDUFAF4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for NDUFAF4 Gene

Protein differential expression in normal tissues from HIPED for NDUFAF4 Gene

This gene is overexpressed in Brain (6.5) and Peripheral blood mononuclear cells (6.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for NDUFAF4 Gene



Protein tissue co-expression partners for NDUFAF4 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for NDUFAF4

SOURCE GeneReport for Unigene cluster for NDUFAF4 Gene:

Hs.512144

Evidence on tissue expression from TISSUES for NDUFAF4 Gene

  • Nervous system(4.8)
  • Blood(4.2)
  • Bone(4)

Phenotype-based relationships between genes and organs from Gene ORGANizer for NDUFAF4 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • endocrine
  • integumentary
  • nervous
  • respiratory
  • skeletal muscle
  • skeleton
Regions:
Head and neck:
  • brain
  • cerebellum
  • cerebrospinal fluid
  • cranial nerve
  • ear
  • eye
  • eyelid
  • face
  • head
  • meninges
  • neck
  • skull
Thorax:
  • esophagus
  • heart
  • heart valve
  • lung
Abdomen:
  • adrenal gland
  • liver
  • stomach
Limb:
  • foot
  • lower limb
General:
  • peripheral nerve
  • peripheral nervous system
  • skin
  • spinal cord
  • sweat gland
genes like me logo Genes that share expression patterns with NDUFAF4: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and mRNA Expression by UniProt/SwissProt for NDUFAF4 Gene

Orthologs for NDUFAF4 Gene

This gene was present in the common ancestor of animals.

Orthologs for NDUFAF4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia NDUFAF4 31 30
  • 99.05 (n)
OneToOne
cow
(Bos Taurus)
Mammalia NDUFAF4 31 30
  • 83.81 (n)
OneToOne
dog
(Canis familiaris)
Mammalia NDUFAF4 31 30
  • 81.9 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Ndufaf4 17 31 30
  • 79.58 (n)
rat
(Rattus norvegicus)
Mammalia Ndufaf4 30
  • 78.74 (n)
oppossum
(Monodelphis domestica)
Mammalia NDUFAF4 31
  • 63 (a)
OneToOne
chicken
(Gallus gallus)
Aves NDUFAF4 31 30
  • 62.3 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia NDUFAF4 31
  • 47 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia ndufaf4 30
  • 60.08 (n)
African clawed frog
(Xenopus laevis)
Amphibia Xl.33349 30
zebrafish
(Danio rerio)
Actinopterygii ndufaf4 31 30
  • 55.29 (n)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta CG11722 31 30
  • 45.55 (n)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP007625 30
  • 43.95 (n)
Species where no ortholog for NDUFAF4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • 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)
  • 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 NDUFAF4 Gene

ENSEMBL:
Gene Tree for NDUFAF4 (if available)
TreeFam:
Gene Tree for NDUFAF4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for NDUFAF4: view image

Paralogs for NDUFAF4 Gene

Pseudogenes.org Pseudogenes for NDUFAF4 Gene

genes like me logo Genes that share paralogs with NDUFAF4: view

No data available for Paralogs for NDUFAF4 Gene

Variants for NDUFAF4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for NDUFAF4 Gene

SNP ID Clinical significance and condition Chr 06 pos Variation AA Info Type
675543 Benign: not provided 96,897,517(-) G/A INTRON_VARIANT
677882 Benign: not provided 96,897,178(-) G/C INTRON_VARIANT
681227 Benign: not provided 96,897,357(-) G/A INTRON_VARIANT
681254 Benign: not provided 96,898,113(-) A/G FIVE_PRIME_UTR_VARIANT
711036 Likely Benign: not provided 96,891,399(-) C/A INTRON_VARIANT

Additional dbSNP identifiers (rs#s) for NDUFAF4 Gene

Structural Variations from Database of Genomic Variants (DGV) for NDUFAF4 Gene

Variant ID Type Subtype PubMed ID
nsv981168 CNV duplication 23825009

Variation tolerance for NDUFAF4 Gene

Residual Variation Intolerance Score: 52.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.52; 11.35% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for NDUFAF4 Gene

Human Gene Mutation Database (HGMD)
NDUFAF4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
NDUFAF4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NDUFAF4 Gene

Disorders for NDUFAF4 Gene

MalaCards: The human disease database

(8) MalaCards diseases for NDUFAF4 Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

NDUF4_HUMAN
  • Mitochondrial complex I deficiency, nuclear type 15 (MC1DN15) [MIM:618237]: A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN15 transmission pattern is consistent with autosomal recessive inheritance. {ECO:0000269 PubMed:18179882, ECO:0000269 PubMed:28853723}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for NDUFAF4

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with NDUFAF4: view

No data available for Genatlas for NDUFAF4 Gene

Publications for NDUFAF4 Gene

  1. Mutations in NDUFAF3 (C3ORF60), encoding an NDUFAF4 (C6ORF66)-interacting complex I assembly protein, cause fatal neonatal mitochondrial disease. (PMID: 19463981) Saada A … Nijtmans LG (American journal of human genetics 2009) 2 3 4 54
  2. C6ORF66 is an assembly factor of mitochondrial complex I. (PMID: 18179882) Saada A … Elpeleg O (American journal of human genetics 2008) 2 3 4 54
  3. NDUFAF4 variants are associated with Leigh syndrome and cause a specific mitochondrial complex I assembly defect. (PMID: 28853723) Baertling F … Nijtmans LGJ (European journal of human genetics : EJHG 2017) 3 4 54
  4. Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression. (PMID: 20877624) Hendrickson SL … O'Brien SJ (PloS one 2010) 3 41 54
  5. HRPAP20: a novel calmodulin-binding protein that increases breast cancer cell invasion. (PMID: 17001319) Karp CM … Buckley AR (Oncogene 2007) 3 4 54

Products for NDUFAF4 Gene

Sources for NDUFAF4 Gene