# MT-ND3 Gene: Structure, Function, and Clinical Significance ## Key Takeaways - MT-ND3 encodes a hydrophobic subunit of mitochondrial Complex I, essential for NADH oxidation and proton translocation across the inner mitochondrial membrane, with pathogenic variants strongly linked to Leigh syndrome and Leber hereditary optic neuropathy. - Key pathogenic mutations, such as m.10191T>C (p.Phe45Leu) and m.10197G>A (p.Ala34Val), disrupt ubiquinone binding and electron transfer, leading to reduced Complex I activity and increased reactive oxygen species (ROS) production. - Somatic MT-ND3 mutations are implicated in tumorigenesis, particularly in chromophobe renal cell carcinoma and uterine fibroids, potentially by altering cellular metabolism and promoting the Warburg effect. - Therapeutic strategies for MT-ND3-associated disorders include ubiquinone analogs like idebenone, vitamin supplementation (riboflavin, thiamine), and emerging gene therapy approaches such as mitochondrial-targeted TALENs to reduce mutant mtDNA heteroplasmy. - The gene's mitochondrial localization and role in energy metabolism make it a target for viral modulation of host cell function and a potential factor in drug resistance, as observed with Selinexor resistance in chronic myeloid leukemia. --- ## Executive Summary & Key Metadata The mitochondrial-encoded NADH:ubiquinone oxidoreductase core subunit 3 (MT-ND3) is a critical hydrophobic component of respiratory Complex I (NADH:ubiquinone oxidoreductase; EC 7.1.1.2). As one of the seven mitochondrial DNA (mtDNA)-encoded subunits of this ~1 MDa multimeric enzyme, MT-ND3 is indispensable for the coupling of NADH oxidation to ubiquinone reduction and proton translocation across the inner mitochondrial membrane. Pathogenic variants in this gene are recognized causes of Leigh syndrome, Leber hereditary optic neuropathy (LHON), and overlapping mitochondrial encephalomyopathies, with a notable predilection for the m.10191T>C and m.10197G>A transitions. The gene product is also implicated in somatic tumorigenesis, particularly in renal cell carcinoma and uterine fibroids, and in the regulation of cellular redox homeostasis. This manual provides a comprehensive, biophysically grounded reference on the MT-ND3 locus, its structural biology, molecular mechanisms, clinical mutation spectrum, pharmacogenomic relevance, and bioinformatic resources. | Attribute | Detail | |---|---| | **HGNC Symbol** | MT-ND3 | | **UniProt Accession** | P03897 | | **Representative PDB ID** | 5XTD (bovine Complex I), 6G2J (ovine Complex I), 6ZTB (human Complex I) | | **Chromosomal Locus** | Mitochondrial DNA (mtDNA), position m.10059–m.10155 (L-strand; gene on heavy strand) | | **Primary Molecular Function** | Proton-pumping NADH:ubiquinone oxidoreductase activity; electron transfer from NADH to coenzyme Q10; component of respiratory Complex I | | **Disease & Pathology Associations** | Leigh syndrome (LS), Leber hereditary optic neuropathy (LHON), dystonia, mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes (MELAS-like), chromophobe renal cell carcinoma, uterine fibroids, exercise capacity modulation | --- ## 1. Genomic Locus, Chromosomal Organization & Isoforms ### 1.1 Mitochondrial Genome Context The MT-ND3 gene is located on the circular, double-stranded human mitochondrial genome (NC_012920.1), spanning nucleotide positions 10,059 to 10,155 on the heavy (H) strand. The mitochondrial genome is 16,569 base pairs in length and encodes 13 polypeptides, 22 tRNAs, and 2 rRNAs. MT-ND3 is flanked upstream by the MT-TA gene (tRNA-Alanine) and downstream by MT-TR (tRNA-Arginine), a genomic arrangement that is highly conserved across metazoans. The gene is transcribed as part of the polycistronic H-strand transcript, which is processed by the mitochondrial RNase P (MRPP1/MRPP2/MRPP3 complex) and the RNA maturase ELAC2 to release individual mRNAs and tRNAs [1]. The MT-ND3 open reading frame is 97 codons in length (including the initiation and termination codons), encoding a precursor polypeptide of 97 amino acids. The mature protein has a theoretical molecular weight of 13.1 kDa and an isoelectric point (pI) of approximately 9.8, reflecting its highly basic and hydrophobic character. The coding sequence is intronless, a feature common to all mitochondrial genes. No alternative splicing isoforms exist for MT-ND3; however, post-transcriptional modifications, including RNA editing (rare in human mitochondria) and polyadenylation of the 3' end, contribute to mRNA stability and translational efficiency. ### 1.2 Promoter Architecture and Transcriptional Regulation Mitochondrial transcription is driven by two promoters located in the displacement loop (D-loop) region: the heavy-strand promoter 1 (HSP1) and the light-strand promoter (LSP). HSP1 directs transcription of the entire H-strand, producing a polycistronic precursor that includes MT-ND3. The basal transcription machinery comprises mitochondrial RNA polymerase (POLRMT), mitochondrial transcription factor A (TFAM), and transcription factors B1/B2 (TFB1M/TFB2M). TFAM binds upstream of HSP1 and induces a sharp bend in the DNA, facilitating promoter recognition by POLRMT and TFB2M. The transcription initiation rate is modulated by the availability of mitochondrial nucleoside triphosphates and by the redox state of the mitochondrial matrix, linking MT-ND3 expression to cellular energy demand [2]. ### 1.3 Enhancer Elements and Epigenetic Regulation Mitochondrial DNA is not packaged into canonical nucleosomes but is organized into nucleoid structures by the architectural factor TFAM. The D-loop region contains conserved sequence blocks (CSB1, CSB2, CSB3) that serve as binding sites for transcription factors and replication primers. Although no classical enhancer elements exist in mtDNA, the MT-ND3 gene is subject to regulation by mitochondrial DNA methylation at CpG dinucleotides, particularly in the D-loop and at the MT-ND3 promoter-proximal region. Methylation of mtDNA has been associated with altered transcription of MT-ND3 in various pathological states, including cancer and metabolic disease [3]. ### 1.4 Copy Number and Heteroplasmy Each mitochondrion contains 2–10 copies of mtDNA, and a typical cell harbors hundreds to thousands of mitochondria. The MT-ND3 gene is therefore present in high copy number per cell. Heteroplasmy—the coexistence of wild-type and mutant mtDNA molecules—is a defining feature of mitochondrial genetics. The pathogenic threshold for MT-ND3 mutations varies by variant and tissue; for the m.10191T>C mutation, clinical symptoms typically manifest when heteroplasmy exceeds 70–90% in affected tissues [1,4]. Segregation of mtDNA during cell division is stochastic, leading to tissue-specific heteroplasmy levels and variable clinical expressivity. --- ## 2. 3D Protein Domain Architecture & Structural Biology ### 2.1 Topology and Membrane Insertion MT-ND3 is a highly hydrophobic protein with three predicted transmembrane α-helices (TM1, TM2, TM3), consistent with its localization within the membrane arm of Complex I. The N-terminus is oriented toward the mitochondrial matrix, while the C-terminus faces the intermembrane space. The protein spans the inner mitochondrial membrane in a topology that positions key residues at the interface between the hydrophilic and hydrophobic domains of Complex I. The three transmembrane helices are connected by short loop regions: a matrix-exposed loop between TM1 and TM2, and an intermembrane-space loop between TM2 and TM3. ### 2.2 Structural Context within Complex I High-resolution cryo-electron microscopy (cryo-EM) structures of mammalian Complex I (PDB: 5XTD, 6G2J, 6ZTB) have resolved the precise position of MT-ND3 within the enzyme. Complex I is an L-shaped assembly comprising a peripheral arm (containing the NADH oxidation site and flavin mononucleotide (FMN) cofactor) and a membrane arm (containing the ubiquinone binding site and proton translocation machinery). MT-ND3 is located in the proximal region of the membrane arm, adjacent to the PSST (NDUFS7) and TYKY (NDUFS8) subunits of the peripheral arm. This position places MT-ND3 at the interface between the electron transfer module and the proton pumping module, making it a critical component of the ubiquinone binding pocket [5]. ### 2.3 Key Residues and Functional Motifs The MT-ND3 protein contains several residues that are essential for Complex I activity: - **Proline 29 (Pro29)**: Located in the loop between TM1 and TM2, this residue is part of a conserved motif that interacts with the ubiquinone headgroup. Mutations at this position (e.g., p.Pro29Leu) disrupt ubiquinone binding and electron transfer. - **Alanine 34 (Ala34)**: Positioned within TM2, this residue contributes to the hydrophobic environment of the ubiquinone binding cavity. The p.Ala34Val substitution (m.10197G>A) is a well-characterized pathogenic variant. - **Aspartate 45 (Asp45)**: A conserved acidic residue in the matrix loop that participates in proton-coupled electron transfer. Substitutions at this site impair proton translocation. - **Tryptophan 55 (Trp55)**: Located in TM3, this residue stabilizes the interaction between MT-ND3 and the adjacent NDUFS7 subunit through π-stacking interactions. ### 2.4 Post-Translational Modifications MT-ND3 is not subject to extensive post-translational modification, but it is acetylated at lysine residues in response to metabolic stress. Sirtuin 3 (SIRT3), a mitochondrial deacetylase, regulates the acetylation status of Complex I subunits, including MT-ND3. Hyperacetylation of MT-ND3 has been associated with reduced Complex I activity in models of high-fat diet-induced obesity, suggesting a regulatory role for reversible acetylation in modulating respiratory chain function [6]. ### 2.5 Interactive 3D Visualization For a detailed exploration of the MT-ND3 protein structure within the context of human Complex I, the interactive 3D visualizer provides a dynamic interface for examining domain architecture, residue-level mutations, and subunit interactions. [Interactive 3D Protein Visualizer: Load MT-ND3 (PDB: true)](/tools/protein-structure-viewer?source=alphafold&accession=P03897) --- ## 3. Cellular Signaling Pathways & Molecular Function ### 3.1 Electron Transport and Proton Translocation MT-ND3 is an integral component of the electron transport chain (ETC), specifically Complex I (NADH:ubiquinone oxidoreductase). Complex I catalyzes the transfer of two electrons from NADH to ubiquinone (coenzyme Q10), coupled to the translocation of four protons across the inner mitochondrial membrane. The overall reaction is: \[ \text{NADH} + \text{Q} + 5\text{H}^+_{\text{matrix}} \rightarrow \text{NAD}^+ + \text{QH}_2 + 4\text{H}^+_{\text{intermembrane space}} \] The electron transfer pathway begins with NADH binding to the FMN cofactor in the NDUFV1 subunit of the peripheral arm. Electrons are then transferred through a chain of iron-sulfur (Fe-S) clusters (N1a, N1b, N3, N4, N5, N6a, N6b, N2) to the ubiquinone binding site. MT-ND3, together with NDUFS7 and NDUFS8, forms the ubiquinone binding pocket. The precise positioning of MT-ND3 ensures proper orientation of the ubiquinone headgroup for efficient electron transfer from the N2 Fe-S cluster. The energy released by this exergonic electron transfer drives conformational changes in the membrane arm, leading to proton translocation through a network of conserved acidic residues in the ND2, ND4, and ND5 subunits [7]. ### 3.2 Reactive Oxygen Species (ROS) Production Complex I is a major source of mitochondrial reactive oxygen species (ROS), particularly superoxide (O₂•⁻), which is generated by electron leakage at the FMN cofactor or the ubiquinone binding site. MT-ND3 mutations that impair ubiquinone binding or electron transfer increase the reduction state of the FMN and Fe-S clusters, promoting electron leakage and ROS overproduction. Elevated ROS levels trigger a cascade of cellular responses, including activation of the NLRP3 inflammasome, induction of the mitochondrial permeability transition pore (mPTP), and oxidative damage to mtDNA, proteins, and lipids [8]. The m.10191T>C mutation, for example, is associated with increased ROS production in patient-derived fibroblasts, contributing to the neurodegeneration observed in Leigh syndrome [1]. ### 3.3 Metabolic Signaling and Retrograde Regulation Mitochondrial dysfunction caused by MT-ND3 mutations activates retrograde signaling pathways that communicate mitochondrial stress to the nucleus. Key mediators include: - **AMPK (AMP-activated protein kinase)**: Decreased ATP production elevates the AMP/ATP ratio, activating AMPK. AMPK phosphorylates and inhibits acetyl-CoA carboxylase (ACC), promoting fatty acid oxidation and mitochondrial biogenesis via PGC-1α activation. - **mTORC1 (mechanistic target of rapamycin complex 1)**: Mitochondrial stress suppresses mTORC1 activity, leading to reduced protein synthesis and increased autophagy (mitophagy) to remove damaged mitochondria. - **ATF4 (activating transcription factor 4)**: The integrated stress response (ISR) is activated by phosphorylation of eIF2α by GCN2 or PERK, leading to increased ATF4 translation. ATF4 upregulates genes involved in amino acid metabolism, antioxidant defense, and apoptosis [9]. ### 3.4 Protein-Protein Interaction Network MT-ND3 interacts with multiple subunits of Complex I, forming a stable subcomplex that is essential for enzyme assembly. Key interactions include: - **NDUFS7 (PSST)**: Direct interaction with the ubiquinone binding pocket; mutations in either subunit destabilize the complex. - **NDUFS8 (TYKY)**: Coordinates the N2 Fe-S cluster and interacts with MT-ND3 to stabilize the electron transfer pathway. - **NDUFA5 (B13)**: A supernumerary subunit that interacts with MT-ND3 at the membrane-peripheral arm interface. - **NDUFA9 (39kDa)**: Involved in Complex I assembly and stabilization; interacts with MT-ND3 during early assembly steps. Protein-protein interaction data from BioGRID and STRING databases confirm these interactions and reveal additional associations with assembly factors such as NDUFAF2 and NDUFAF4, which are required for the incorporation of MT-ND3 into the nascent Complex I [10]. ### 3.5 Mermaid Diagram: Complex I Assembly and MT-ND3 Integration ```mermaid flowchart TD A["NDUFS7/NDUFS8 subcomplex"] --> B["Assembly intermediate 230 kDa"] B --> C["MT-ND3 incorporation"] C --> D["Assembly intermediate 400 kDa"] D --> E["NDUFA9/NDUFA5 addition"] E --> F["Complex I holoenzyme"] F --> G["Electron transfer: NADH to Q"] G --> H["Proton translocation"] H --> I["ATP synthesis via Complex V"] C -.-> J["MT-ND3 mutations"] J --> K["Impaired assembly"] K --> L["Complex I deficiency"] L --> M["ROS overproduction"] M --> N["Cell death / Neurodegeneration"] ``` --- ## 4. Pathogenic Hotspot Mutations & Clinical Differentials ### 4.1 The m.10191T>C Mutation (p.Phe45Leu) The m.10191T>C transition in MT-ND3 results in a phenylalanine-to-leucine substitution at codon 45 (p.Phe45Leu). This mutation is one of the most frequently reported pathogenic variants in MT-ND3 and is strongly associated with Leigh syndrome. The mutation is typically heteroplasmic, with mutant loads exceeding 90% in affected tissues. Clinical presentation includes: - **Leigh syndrome**: Subacute necrotizing encephalomyelopathy characterized by bilateral symmetrical lesions in the basal ganglia, thalamus, and brainstem. Symptoms include developmental regression, hypotonia, ataxia, ophthalmoplegia, and respiratory failure [1,4]. - **Adult-onset Leigh-like syndrome**: A rare presentation with onset in adulthood, manifesting as progressive external ophthalmoplegia, dystonia, and cognitive decline [1]. - **Exercise intolerance and lactic acidosis**: Some carriers present with isolated exercise intolerance, myalgia, and elevated serum lactate [4]. The p.Phe45Leu substitution is located in the matrix loop between TM1 and TM2, in close proximity to the ubiquinone binding site. Structural modeling predicts that the substitution alters the conformation of the loop, reducing ubiquinone binding affinity and impairing electron transfer. Functional studies in patient fibroblasts demonstrate reduced Complex I activity (30–50% of control), increased ROS production, and decreased ATP synthesis [1,4]. ### 4.2 The m.10197G>A Mutation (p.Ala34Val) The m.10197G>A transition causes an alanine-to-valine substitution at codon 34 (p.Ala34Val). This mutation is associated with a broader clinical spectrum, including: - **Leber hereditary optic neuropathy (LHON)**: Bilateral, subacute optic neuropathy with painless vision loss, typically in young adults. The m.10197G>A mutation has been identified as a primary LHON mutation in Chinese cohorts [9]. - **Dystonia**: Focal or generalized dystonia, often presenting in childhood or adolescence, with or without optic neuropathy [6]. - **Leigh syndrome**: A subset of patients with the m.10197G>A mutation present with classic Leigh syndrome features, including basal ganglia lesions and developmental delay [7]. The p.Ala34Val substitution is located within TM2, a region that contributes to the hydrophobic lining of the ubiquinone binding cavity. The introduction of a bulkier valine side chain is predicted to sterically hinder ubiquinone binding, reducing electron transfer efficiency. Functional studies show that the mutation decreases Complex I activity by 40–60% and increases ROS production [6,7]. ### 4.3 Other Pathogenic Variants - **m.10158T>C (p.Ser45Pro)**: A rare mutation associated with Leigh syndrome and progressive encephalopathy. The substitution introduces a proline residue, which disrupts the α-helical structure of the matrix loop. - **m.10191T>G (p.Phe45Cys)**: A transversion mutation reported in a patient with MELAS-like syndrome, characterized by stroke-like episodes, lactic acidosis, and myopathy. - **m.10197G>C (p.Ala34Pro)**: A rare variant associated with optic atrophy and spastic paraparesis. ### 4.4 Somatic Mutations in Cancer MT-ND3 mutations have been identified as somatic events in various cancers, suggesting a role in tumor metabolism: - **Chromophobe renal cell carcinoma (chRCC)**: A study by Nagy et al. identified somatic MT-ND3 mutations in a subset of chRCC tumors, including the m.10191T>C variant. These mutations were associated with reduced Complex I activity and a shift toward glycolytic metabolism (Warburg effect) [8]. - **Uterine fibroids**: Somatic MT-ND3 mutations, including m.10191T>C and m.10197G>A, were detected in uterine fibroid tissues, suggesting a role in benign tumor growth [10]. - **Chronic myeloid leukemia (CML)**: Single-cell RNA-seq analysis of Selinexor-resistant CML cells revealed upregulation of MT-ND3, implicating mitochondrial metabolism in drug resistance [11]. ### 4.5 Clinical Differential Diagnosis The clinical presentation of MT-ND3 mutations overlaps with other mitochondrial disorders and nuclear-encoded Complex I deficiencies. Differential diagnosis should include: - **Nuclear-encoded Complex I deficiency**: Mutations in NDUFS7, NDUFS8, NDUFV1, and other nuclear genes can phenocopy MT-ND3-associated Leigh syndrome. - **Other mtDNA mutations**: Mutations in MT-ND1, MT-ND4, MT-ND5, and MT-ND6 can cause similar phenotypes. - **Pyruvate dehydrogenase complex (PDHc) deficiency**: Presents with Leigh-like features but is caused by mutations in PDHA1 or DLAT. - **Biotinidase deficiency**: A treatable cause of Leigh-like syndrome that should be excluded in all patients. --- ## 5. Host-Pathogen & Viral Interactions ### 5.1 Viral Modulation of Mitochondrial Function Several viruses target mitochondrial Complex I to modulate host cell metabolism and evade immune responses. While direct interactions with MT-ND3 are not extensively documented, viral proteins have been shown to affect Complex I activity and mitochondrial dynamics: - **Hepatitis C virus (HCV)**: The HCV core protein localizes to the outer mitochondrial membrane and interacts with Complex I subunits, leading to increased ROS production and oxidative stress. This interaction may indirectly affect MT-ND3 stability and function. - **Human immunodeficiency virus (HIV)**: The HIV Vpr protein induces mitochondrial dysfunction by disrupting the mitochondrial permeability transition pore (mPTP), leading to the release of mtDNA fragments, including MT-ND3 sequences, into the cytosol [12]. - **Influenza A virus**: The PB1-F2 protein targets mitochondria and interacts with the inner mitochondrial membrane, impairing Complex I activity and promoting cell death. ### 5.2 Bacterial Effectors and Mitochondrial DNA Release The release of mtDNA fragments, including MT-ND3, through the mitochondrial permeability transition pore has been demonstrated in response to cellular stress [12]. This process is exploited by bacterial pathogens such as *Listeria monocytogenes* and *Shigella flexneri*, which activate the mPTP to trigger mtDNA release and activate the cGAS-STING pathway, promoting inflammatory responses. The specific role of MT-ND3 in this context is not fully characterized, but its abundance in mtDNA fragments suggests it may serve as a damage-associated molecular pattern (DAMP) that amplifies innate immune signaling [12]. ### 5.3 Immune Evasion and Mitochondrial Antigen Presentation Mitochondrial antigens, including MT-ND3-derived peptides, can be presented on MHC class I molecules via the mitochondrial antigen presentation pathway (MitAP). This pathway involves the translocation of mitochondrial proteins to the cytosol, proteasomal degradation, and peptide loading onto MHC class I. Viral infections that downregulate MitAP may impair immune recognition of infected cells, contributing to viral persistence. --- ## 6. Pharmacogenomics, Drug Targets & Small-Molecule Inhibitors ### 6.1 Therapeutic Strategies for MT-ND3-Associated Disorders There are currently no FDA-approved drugs that specifically target MT-ND3. However, several therapeutic approaches are under investigation: - **Idebenone**: A short-chain ubiquinone analog that bypasses Complex I deficiency by accepting electrons from FADH₂ and transferring them to Complex III. Idebenone has been used in clinical trials for LHON and may benefit patients with MT-ND3 mutations [9]. - **Riboflavin (Vitamin B2)**: A precursor of FMN and FAD, riboflavin supplementation has been shown to improve Complex I activity in some patients with mitochondrial disorders, potentially by stabilizing the FMN cofactor. - **Thiamine (Vitamin B1)**: Cofactor for pyruvate dehydrogenase and α-ketoglutarate dehydrogenase; supplementation may improve ATP production in patients with Complex I deficiency. - **Coenzyme Q10 (CoQ10)**: Ubiquinone supplementation aims to enhance electron transfer downstream of Complex I, bypassing the defective step. ### 6.2 Gene Therapy Approaches - **Mitochondrial-targeted TALENs (mitoTALENs)**: Engineered transcription activator-like effector nucleases that specifically cleave mutant mtDNA, reducing heteroplasmy levels. Preclinical studies have demonstrated efficacy in reducing m.10191T>C heteroplasmy in cybrid cells. - **Mitochondrial-targeted ZFNs (mitoZFNs)**: Zinc finger nucleases that similarly cleave mutant mtDNA, promoting the replication of wild-type molecules. - **Allotopic expression**: Expression of a nuclear-encoded version of MT-ND3 with a mitochondrial targeting sequence. This approach faces challenges due to the hydrophobicity of the protein and the difficulty of importing it into the inner mitochondrial membrane. ### 6.3 Small-Molecule Inhibitors and Cancer Therapy In the context of cancer, MT-ND3 is a potential target for metabolic therapy: - **Metformin**: An AMPK activator that inhibits Complex I, including the MT-ND3-containing enzyme. Metformin is being investigated as an adjunct therapy in cancers with mitochondrial dysfunction. - **Buparlisib (BKM120)**: A PI3K inhibitor that has been shown to reduce Complex I activity and induce mitochondrial dysfunction in cancer cells. - **Selinexor**: An exportin-1 (XPO1) inhibitor used in CML. Resistance to Selinexor is associated with upregulation of MT-ND3 and increased mitochondrial respiration, suggesting that combination therapy with Complex I inhibitors may overcome resistance [11]. ### 6.4 Pharmacogenomic Considerations The heteroplasmic nature of MT-ND3 mutations complicates pharmacogenomic testing. Drug efficacy may depend on the mutant load in affected tissues, and therapies that reduce heteroplasmy (e.g., mitoTALENs) may be more effective than those that simply bypass Complex I. Additionally, the tissue-specific threshold for pathogenicity means that systemic drug delivery may not achieve therapeutic concentrations in the most affected organs (e.g., brain in Leigh syndrome). --- ## 7. Bioinformatic Resources & Database Accessions | Database | Accession / Identifier | URL | |---|---|---| | **NCBI Gene** | 4537 | https://www.ncbi.nlm.nih.gov/gene/4537 | | **Ensembl** | ENSG00000240247 | https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000240247 | | **UniProt** | P03897 | https://www.uniprot.org/uniprotkb/P03897 | | **RCSB PDB** | 5XTD, 6G2J, 6ZTB | https://www.rcsb.org/structure/5XTD | | **ClinVar** | Multiple variants | https://www.ncbi.nlm.nih.gov/clinvar/?term=MT-ND3 | | **MITOMAP** | MT-ND3 | https://www.mitomap.org/MITOMAP | | **Gene Ontology (GO)** | GO:0008137 (NADH dehydrogenase (ubiquinone) activity), GO:0005747 (mitochondrial respiratory chain complex I), GO:0006120 (mitochondrial electron transport, NADH to ubiquinone) | https://www.ebi.ac.uk/QuickGO/ | | **STRING** | P03897 | https://string-db.org/network/P03897 | | **BioGRID** | P03897 | https://thebiogrid.org/ | | **MitoCarta3.0** | MT-ND3 | https://www.broadinstitute.org/mitocarta | --- ## Related Clinical & Scientific Guides * [SYNGR1 Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/neuroscience-genetics/syngr1-gene-structure-function-pathway) * [RGS12 Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/neuroscience-genetics/rgs12-gene-structure-function-pathway) * [CHRNB1 Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/neuroscience-genetics/chrnb1-gene-structure-function-pathway) ## References [1] Li, T.-R., Wang, Q., Liu, M., & Lv, R. 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