NDUFS8 (NADH:ubiquinone oxidoreductase core subunit S8)

Gene

• Entrez ID: 4728
• Gene name: NADH:ubiquinone oxidoreductase core subunit S8
• Gene symbol: NDUFS8
• Synonyms (NCBI Gene): CI-23k, CI23KD, MC1DN2, TYKY
• Chromosome: 11
• Chromosome location: 11q13.2
• Summary: This gene encodes a subunit of mitochondrial NADH:ubiquinone oxidoreductase, or Complex I, a multimeric enzyme of the respiratory chain responsible for NADH oxidation, ubiquinone reduction, and the ejection of protons from mitochondria. The encoded protei

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs111033588	G>A	Pathogenic	Missense variant, coding sequence variant
rs143337739	G>A	Likely-pathogenic, uncertain-significance	Coding sequence variant, missense variant
rs397514617	C>A	Pathogenic	Missense variant, coding sequence variant
rs750075208	G>A	Likely-pathogenic	Coding sequence variant, missense variant
rs863224115	A>T	Likely-pathogenic	Missense variant, coding sequence variant
rs1267554976	G>A,C	Likely-pathogenic	Coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT029672	hsa-miR-26b-5p	Microarray	19088304

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0003954	Function	NADH dehydrogenase activity	IBA
GO:0003954	Function	NADH dehydrogenase activity	IMP	14749350, 15159508
GO:0005515	Function	Protein binding	IPI	31536960
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IDA	9666055
GO:0005739	Component	Mitochondrion	IEA
GO:0005743	Component	Mitochondrial inner membrane	IDA	28844695
GO:0005743	Component	Mitochondrial inner membrane	IEA
GO:0005743	Component	Mitochondrial inner membrane	IEA
GO:0005759	Component	Mitochondrial matrix	TAS
GO:0006120	Process	Mitochondrial electron transport, NADH to ubiquinone	IBA
GO:0006120	Process	Mitochondrial electron transport, NADH to ubiquinone	IMP	22499348
GO:0006120	Process	Mitochondrial electron transport, NADH to ubiquinone	NAS	9666055, 9878551
GO:0008137	Function	NADH dehydrogenase (ubiquinone) activity	IEA
GO:0008137	Function	NADH dehydrogenase (ubiquinone) activity	IMP	9837812
GO:0008137	Function	NADH dehydrogenase (ubiquinone) activity	IMP	22499348
GO:0008137	Function	NADH dehydrogenase (ubiquinone) activity	NAS	9878551
GO:0009060	Process	Aerobic respiration	NAS	30030361
GO:0016020	Component	Membrane	IEA
GO:0016491	Function	Oxidoreductase activity	IEA
GO:0016651	Function	Oxidoreductase activity, acting on NAD(P)H	IEA
GO:0032981	Process	Mitochondrial respiratory chain complex I assembly	IBA
GO:0032981	Process	Mitochondrial respiratory chain complex I assembly	IMP	11112787, 15159508, 22499348
GO:0042776	Process	Proton motive force-driven mitochondrial ATP synthesis	NAS	30030361
GO:0045271	Component	Respiratory chain complex I	IBA
GO:0045271	Component	Respiratory chain complex I	IDA	12611891, 31536960
GO:0045271	Component	Respiratory chain complex I	IEA
GO:0045271	Component	Respiratory chain complex I	IMP	11112787
GO:0045271	Component	Respiratory chain complex I	NAS	9878551
GO:0046872	Function	Metal ion binding	IEA
GO:0051536	Function	Iron-sulfur cluster binding	IEA
GO:0051539	Function	4 iron, 4 sulfur cluster binding	IEA
GO:1902600	Process	Proton transmembrane transport	IEA

Other IDs

• MIM: 602141
• HGNC: 7715
• e!Ensembl: ENSG00000110717

Protein

• UniProt ID: O00217
• Protein name: NADH dehydrogenase [ubiquinone] iron-sulfur protein 8, mitochondrial (EC 7.1.1.2) (Complex I-23kD) (CI-23kD) (NADH-ubiquinone oxidoreductase 23 kDa subunit) (TYKY subunit)
• Protein function: Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor (PubMed:22499348). Essential for the
• PDB: 5XTB, 5XTD, 5XTH, 5XTI
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF12838	Fer4_7	110 → 164	4Fe-4S dicluster domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed in all tissues with the highest level in heart and skeletal muscle and the lowest level in lung. {ECO:0000269|PubMed:9666055}.
• Sequence:

  MRCLTTPMLLRALAQAARAGPPGGRSLHSSAVAATYKYVNMQDPEMDMKSVTDRAARTLL
  WTELFRGLGMTLSYLFREPATINYPFEKGPLSPRFRGEHALRRYPSGEERCIACKLCEAI
  CPAQAITIEAEPRADGSRRTTRYDIDMTKCIYCGFCQEACPVDAIVEGPNFEFSTETHEE
  LLYNKEKLLNNGDKWEAEIAANIQADYLYR

• Sequence length: 210

Pathways

KEGG:

Oxidative phosphorylation
Metabolic pathways
Thermogenesis
Retrograde endocannabinoid signaling
Non-alcoholic fatty liver disease
Alzheimer disease
Parkinson disease
Amyotrophic lateral sclerosis
Huntington disease
Prion disease
Pathways of neurodegeneration - multiple diseases
Chemical carcinogenesis - reactive oxygen species
Diabetic cardiomyopathy

Reactome:

Respiratory electron transport
Complex I biogenesis

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Leigh syndrome	Likely pathogenic	rs28939679, rs1267554976	RCV000762861 RCV000578254	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Mitochondrial complex I deficiency, nuclear type 2	Likely pathogenic; Pathogenic	rs370053943, rs2495581254, rs28939679, rs121912639, rs758247003, rs2495581454, rs775708906, rs397514617, rs397514618	RCV002468753 RCV002470355 RCV000007941 RCV000007943 RCV003324450 RCV003988300 RCV004595007 RCV000033055 RCV000033056	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
LEIGH SYNDROME WITH LEUKODYSTROPHY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mitochondrial complex I deficiency	Uncertain significance	ClinVar Disgenet, GenCC Disgenet, GenCC	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Mitochondrial complex I deficiency, nuclear type 1	Benign; Likely benign; Conflicting classifications of pathogenicity; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MITOCHONDRIAL DISEASE	—	ClinGen, GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MITOCHONDRIAL DISEASES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NDUFS8-related disorder	Conflicting classifications of pathogenicity; Likely benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OSTEOARTHRITIS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adrenocortical Carcinoma	Adrenocortical carcinoma	Pubtator	20231622	Associate	★☆☆☆☆ Found in Text Mining only
Anemia	Anemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Blepharoptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	12079511	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma of lung	Lung carcinoma	BEFREE	27516145		★☆☆☆☆ Found in Text Mining only
Degenerative polyarthritis	Arthritis	CTD_human_DG	18784066		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes Mellitus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dysarthria	Dysarthria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dyskinetic syndrome	Dyskinetic Syndrome	HPO_DG			★☆☆☆☆ Found in Text Mining only
Encephalopathies	Epileptic encephalopathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypertrichosis	HYPERTRICHOSIS	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypertrophic Cardiomyopathy	Hypertrophic cardiomyopathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypoglycemia	Hypoglycemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Isolated complex I deficiency	Isolated Complex I Deficiency	Orphanet			★☆☆☆☆ Found in Text Mining only
Leigh Disease	Leigh Syndrome	BEFREE	11004438, 15159508, 9837812		★☆☆☆☆ Found in Text Mining only
Leigh Disease	Leigh syndrome	Pubtator	11004438, 20819849, 34204592, 36675121, 9837812	Associate	★☆☆☆☆ Found in Text Mining only
Leigh Disease	Leigh Syndrome	CLINGEN_DG	15159508, 19672299, 20818383, 21924235, 22200994, 23430795, 27509854, 29285794, 9837812		★☆☆☆☆ Found in Text Mining only
Leigh Disease	Leigh Syndrome	GENOMICS_ENGLAND_DG	27604308		★☆☆☆☆ Found in Text Mining only
Leigh Disease	Leigh Syndrome	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
LEIGH SYNDROME DUE TO MITOCHONDRIAL COMPLEX I DEFICIENCY	Leigh Syndrome	CLINGEN_DG	15159508, 19672299, 20818383, 21924235, 22200994, 23430795, 27509854, 29285794, 9837812		★☆☆☆☆ Found in Text Mining only
LEIGH SYNDROME DUE TO MITOCHONDRIAL COMPLEX I DEFICIENCY	Leigh Syndrome	GENOMICS_ENGLAND_DG	25655951, 9837812		★☆☆☆☆ Found in Text Mining only
Leigh Syndrome Due To Mitochondrial Complex II Deficiency	Leigh Syndrome	CLINGEN_DG	15159508, 19672299, 20818383, 21924235, 22200994, 23430795, 27509854, 29285794, 9837812		★☆☆☆☆ Found in Text Mining only
Leigh Syndrome due to Mitochondrial Complex III Deficiency	Leigh Syndrome	CLINGEN_DG	15159508, 19672299, 20818383, 21924235, 22200994, 23430795, 27509854, 29285794, 9837812		★☆☆☆☆ Found in Text Mining only
Leigh Syndrome due to Mitochondrial Complex IV Deficiency	Leigh Syndrome	CLINGEN_DG	15159508, 19672299, 20818383, 21924235, 22200994, 23430795, 27509854, 29285794, 9837812		★☆☆☆☆ Found in Text Mining only
Leigh Syndrome due to Mitochondrial Complex V Deficiency	Leigh Syndrome	CLINGEN_DG	15159508, 19672299, 20818383, 21924235, 22200994, 23430795, 27509854, 29285794, 9837812		★☆☆☆☆ Found in Text Mining only
Leigh syndrome with leukodystrophy	Leigh Syndrome With Leukodystrophy	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Leukodystrophy	Leukodystrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Leukoencephalopathy	Leukoencephalopathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Liver Neoplasms	Liver neoplasm	Pubtator	12079511	Associate	★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Lung neoplasms	Pubtator	27516145	Associate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of lung	Lung Cancer	BEFREE	27516145		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	31280487		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Mitochondrial complex I deficiency	Mitochondrial complex deficiency	Pubtator	18435906, 27516145, 34204592	Associate	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
MITOCHONDRIAL COMPLEX I DEFICIENCY	Mitochondrial Complex Deficiency	ORPHANET_DG	22499348, 22644603		★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
MITOCHONDRIAL COMPLEX I DEFICIENCY	Mitochondrial Complex Deficiency	GENOMICS_ENGLAND_DG			★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
MITOCHONDRIAL COMPLEX I DEFICIENCY, NUCLEAR TYPE 2	Mitochondrial Complex Deficiency	UNIPROT_DG	15159508, 22499348, 9837812		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
MITOCHONDRIAL COMPLEX I DEFICIENCY, NUCLEAR TYPE 2	Mitochondrial Complex Deficiency	GENOMICS_ENGLAND_DG	9837812		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
MITOCHONDRIAL COMPLEX I DEFICIENCY, NUCLEAR TYPE 2	Mitochondrial Complex Deficiency	CLINVAR_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Mitochondrial Diseases	Mitochondrial Diseases	GENOMICS_ENGLAND_DG	27604308		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mitochondrial Diseases	Mitochondrial Diseases	BEFREE	29285794		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mitochondrial Diseases	Mitochondrial disease	Pubtator	29288336	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mitochondrial Encephalomyopathies	Mitochondrial encephalomyopathy	Pubtator	34204592	Associate	★☆☆☆☆ Found in Text Mining only
Mitochondrial Myopathies	Mitochondrial myopathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Mood swings	Mood swings	HPO_DG			★☆☆☆☆ Found in Text Mining only
Necrotizing encephalopathy, infantile subacute, of Leigh	Necrotizing encephalomyelopathy	CLINGEN_DG	15159508, 19672299, 20818383, 21924235, 22200994, 23430795, 27509854, 29285794, 9837812		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	18324346, 27516145		★☆☆☆☆ Found in Text Mining only
Neurodegenerative Disorders	Neurodegenerative Disorders	BEFREE	11004438		★☆☆☆☆ Found in Text Mining only
Non-Small Cell Lung Carcinoma	Lung carcinoma	BEFREE	27516145		★☆☆☆☆ Found in Text Mining only
Nystagmus	Nystagmus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Optic Atrophy	Optic Atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Osteoarthrosis Deformans	Osteoarthrosis Deformans	CTD_human_DG	18784066		★☆☆☆☆ Found in Text Mining only
Peripheral Nervous System Diseases	Nervous System Diseases	HPO_DG			★☆☆☆☆ Found in Text Mining only
Progressive cerebellar ataxia	Cerebellar Ataxia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Retinitis Pigmentosa	Retinitis Pigmentosa	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sensorineural Hearing Loss (disorder)	Hearing Loss	HPO_DG			★☆☆☆☆ Found in Text Mining only
Severe intellectual disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Strabismus	Strabismus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ventricular Septal Defects	Ventricular septal defect	HPO_DG			★☆☆☆☆ Found in Text Mining only