Human Gene MT-ND4 (ENST00000361381.2) from GENCODE V44
  Description: Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) that is believed to belong to the minimal assembly required for catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone (By similarity). (from UniProt P03905)
Gencode Transcript: ENST00000361381.2
Gencode Gene: ENSG00000198886.2
Transcript (Including UTRs)
   Position: hg38 chrM:10,760-12,137 Size: 1,378 Total Exon Count: 1 Strand: +
Coding Region
   Position: hg38 chrM:10,760-12,137 Size: 1,378 Coding Exon Count: 1 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsMicroarray Expression
Protein StructureOther SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther Names
GeneReviewsMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chrM:10,760-12,137)mRNA (may differ from genome)Protein (459 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
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-  Comments and Description Text from UniProtKB
  ID: NU4M_HUMAN
DESCRIPTION: RecName: Full=NADH-ubiquinone oxidoreductase chain 4; EC=1.6.5.3; AltName: Full=NADH dehydrogenase subunit 4;
FUNCTION: Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) that is believed to belong to the minimal assembly required for catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone (By similarity).
CATALYTIC ACTIVITY: NADH + ubiquinone = NAD(+) + ubiquinol.
SUBCELLULAR LOCATION: Mitochondrion membrane; Multi-pass membrane protein (By similarity).
DISEASE: Defects in MT-ND4 are a cause of Leber hereditary optic neuropathy (LHON) [MIM:535000]. LHON is a maternally inherited disease resulting in acute or subacute loss of central vision, due to optic nerve dysfunction. Cardiac conduction defects and neurological defects have also been described in some patients. LHON results from primary mitochondrial DNA mutations affecting the respiratory chain complexes.
DISEASE: Defects in MT-ND4 are a cause of Leber hereditary optic neuropathy with dystonia (LDYT) [MIM:500001]; also called familial dystonia with visual failure and striatal lucencies. LDYT is part of a spectrum of Leber hereditary optic neuropathy. It is characterized by the association of optic atrophy and central vision loss with dystonia.
DISEASE: Defects in MT-ND4 are a cause of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes syndrome (MELAS) [MIM:540000]. MELAS is a genetically heterogenious disorder, characterized by episodic vomiting, seizures, and recurrent cerebral insults resembling strokes and causing hemiparesis, hemianopsia, or cortical blindness.
SIMILARITY: Belongs to the complex I subunit 4 family.
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/MT-ND4";

-  Primer design for this transcript
 

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-  MalaCards Disease Associations
  MalaCards Gene Search: MT-ND4
Diseases sorted by gene-association score: mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes* (1075), leber optic atrophy* (765), leber hereditary optic neuropathy with dystonia* (516), leigh syndrome* (178), mitochondrial dna-associated leigh syndrome and narp* (76), mitochondrial complex i deficiency* (73), mitochondrial disorders* (25), lactic acidosis (22), neuropathy (20), optic nerve disease (19), colon neuroendocrine neoplasm (16), cranial nerve disease (14), mitochondrial encephalomyopathy (12), deafness, mitochondrial, modifier of* (11), nutritional optic neuropathy (11), partial optic atrophy (11), encephalomyopathy (10), optic neuritis (10), atrial tachyarrhythmia with short pr interval (9), peripheral nervous system disease (8), scotoma (8), retinitis pigmentosa 38 (7), optic atrophy plus syndrome (6), sparganosis (6), dystonia (6), cercarial dermatitis (6), neuritis (6), exposure keratitis (6), blue color blindness (5), carrion's disease (5), kearns-sayre syndrome (5), amblyopia (4), 3-methylglutaconic aciduria, type v (4), myoclonic epilepsy associated with ragged-red fibers (3), mitochondrial metabolism disease (3), nervous system disease (1), retinitis pigmentosa (1)
* = Manually curated disease association

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR010227 - NADH_Q_OxRdtase_chainM/4
IPR001750 - NADH_UbQ/plastoQ_OxRdtase
IPR003918 - NADH_UbQ_OxRdtase
IPR000260 - NADH_UbQ_OxRdtase_chain4_N

Pfam Domains:
PF00361 - Proton-conducting membrane transporter
PF01059 - NADH-ubiquinone oxidoreductase chain 4, amino terminus

ModBase Predicted Comparative 3D Structure on P03905
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserGenome BrowserGenome BrowserGenome BrowserNo ortholog
Gene Details     
Gene Sorter     
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Protein SequenceProtein SequenceProtein SequenceProtein SequenceProtein Sequence 
AlignmentAlignmentAlignmentAlignmentAlignment 

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0008137 NADH dehydrogenase (ubiquinone) activity
GO:0016491 oxidoreductase activity

Biological Process:
GO:0001666 response to hypoxia
GO:0001701 in utero embryonic development
GO:0006120 mitochondrial electron transport, NADH to ubiquinone
GO:0007568 aging
GO:0021549 cerebellum development
GO:0032981 mitochondrial respiratory chain complex I assembly
GO:0035094 response to nicotine
GO:0042773 ATP synthesis coupled electron transport
GO:0045471 response to ethanol
GO:0055114 oxidation-reduction process

Cellular Component:
GO:0005739 mitochondrion
GO:0005743 mitochondrial inner membrane
GO:0005747 mitochondrial respiratory chain complex I
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0031966 mitochondrial membrane
GO:0070469 respiratory chain


-  Descriptions from all associated GenBank mRNAs
  LP895143 - Sequence 7 from Patent EP3253886.
BC061915 - Homo sapiens cDNA clone IMAGE:3887455, **** WARNING: chimeric clone ****.
BX648054 - Homo sapiens mRNA; cDNA DKFZp686F02203 (from clone DKFZp686F02203).
X64709 - H.sapiens deleted mitochondrial mRNA sequence (transcribed in human colon adenocarcinoma cells).
LF205160 - JP 2014500723-A/12663: Polycomb-Associated Non-Coding RNAs.
MA440737 - JP 2018138019-A/12663: Polycomb-Associated Non-Coding RNAs.
AF253979 - Homo sapiens DC24 mRNA, complete cds.
BX647504 - Homo sapiens mRNA; cDNA DKFZp686F22154 (from clone DKFZp686F22154).
BC014376 - Homo sapiens, Similar to NADH dehydrogenase 4, clone IMAGE:4041417, mRNA.
AK097322 - Homo sapiens cDNA FLJ40003 fis, clone STOMA2003716.
BC002852 - Homo sapiens mRNA similar to zinc finger protein 232 (cDNA clone IMAGE:3634328).
AK000624 - Homo sapiens cDNA FLJ20617 fis, clone KAT05223.
AK128886 - Homo sapiens cDNA fis, clone BRACE2044510, highly similar to Mitochondria NADH-UBIQUINONE OXIDOREDUCTASE CHAIN 4L.
BC006100 - Homo sapiens cDNA clone IMAGE:3952593, **** WARNING: chimeric clone ****.
JD082582 - Sequence 63606 from Patent EP1572962.
JD306710 - Sequence 287734 from Patent EP1572962.
JD306711 - Sequence 287735 from Patent EP1572962.
HV963890 - JP 2012521745-A/34: Aberrant Mitochondrial DNA, Associated Fusion Transcripts and Translation Products and Hybridization Probes Therefor.
HW291275 - JP 2013520965-A/37: UV ASSOCIATED mtDNA FUSION TRANSCRIPTS AND METHODS AND USES THEREOF.
JA760615 - Sequence 34 from Patent EP2411522.
JB242133 - Sequence 37 from Patent EP2542680.
LP790416 - Sequence 34 from Patent EP3272871.
LP803423 - Sequence 37 from Patent EP3305902.
JD053473 - Sequence 34497 from Patent EP1572962.
BC016776 - Homo sapiens, clone IMAGE:4102207, mRNA.
BC016827 - Homo sapiens, clone IMAGE:4109203, mRNA.
AY326467 - Homo sapiens putative protein STRF6 (STRF6) mRNA, complete cds.
AF212044 - Homo sapiens potential LAG1 interactor mRNA, partial cds.
JD417543 - Sequence 398567 from Patent EP1572962.
AK129724 - Homo sapiens cDNA FLJ26213 fis, clone ADG07906.
JD098240 - Sequence 79264 from Patent EP1572962.
JD552968 - Sequence 533992 from Patent EP1572962.
JD510335 - Sequence 491359 from Patent EP1572962.
JD248968 - Sequence 229992 from Patent EP1572962.
LF317166 - JP 2014500723-A/124669: Polycomb-Associated Non-Coding RNAs.
MA552743 - JP 2018138019-A/124669: Polycomb-Associated Non-Coding RNAs.
JD130443 - Sequence 111467 from Patent EP1572962.
JD145041 - Sequence 126065 from Patent EP1572962.
JD093393 - Sequence 74417 from Patent EP1572962.
Y17178 - Homo sapiens mRNA from HIV-associated non-Hodgkin's lymphoma (clone hl2-383).
JD131406 - Sequence 112430 from Patent EP1572962.
JD512886 - Sequence 493910 from Patent EP1572962.
Y17180 - Homo sapiens mRNA from HIV-associated non-Hodgkin's lymphoma (clone hl2-498).
Y17172 - Homo sapiens mRNA from HIV-associated non-Hodgkin's lymphoma (clone hl2-22).
AJ270690 - Homo sapiens partial unknown mRNA from drug-resistant melanoma cells, 3'UTR, clone DSM-6.
JD115202 - Sequence 96226 from Patent EP1572962.
JD461171 - Sequence 442195 from Patent EP1572962.
Y17176 - Homo sapiens mRNA from HIV-associated non-Hodgkin's lymphoma (clone hl2-264).
Y16707 - Homo sapiens mRNA from HIV associated non-Hodgkin's lymphoma (clone hl1-79).
JD286110 - Sequence 267134 from Patent EP1572962.
Y17173 - Homo sapiens mRNA from HIV-associated non-Hodgkin's lymphoma (clone hl2-253).
JD292053 - Sequence 273077 from Patent EP1572962.
JD267297 - Sequence 248321 from Patent EP1572962.
JD127557 - Sequence 108581 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  BioCyc Knowledge Library
PWY-3781 - aerobic respiration I (cytochrome c)

Reactome (by CSHL, EBI, and GO)

Protein P03905 (Reactome details) participates in the following event(s):

R-HSA-6799197 ND4, ND5 bind the 550kDa complex to form the 815kDa complex
R-HSA-6799179 Peripheral arm subunits bind the 815kDa complex to form a 980kDa complex
R-HSA-6799196 The MCIA complex, NDUFAF2-7 all dissociate from the 980kDa complex, resulting in Complex I
R-HSA-163217 Complex I oxidises NADH to NAD+, reduces CoQ to QH2
R-HSA-6799198 Complex I biogenesis
R-HSA-611105 Respiratory electron transport
R-HSA-163200 Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.
R-HSA-1428517 The citric acid (TCA) cycle and respiratory electron transport
R-HSA-1430728 Metabolism

-  Other Names for This Gene
  Alternate Gene Symbols: AK128886, ENST00000361381.1, MTND4, NADH4, ND4, NU4M_HUMAN, P03905, Q6RL39, Q6RQN9, Q8HNR8, uc064xpj.1
UCSC ID: ENST00000361381.2
Representative RNA: AK128886
Protein: P03905 (aka NU4M_HUMAN)

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene MT-ND4:
lhon (Leber Hereditary Optic Neuropathy)
mt-overview (Primary Mitochondrial Disorders Overview)
narp (Mitochondrial DNA-Associated Leigh Syndrome and NARP)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.