NDUFAF6 (NADH:ubiquinone oxidoreductase complex assembly factor 6)

Gene

• Entrez ID: 137682
• Gene name: NADH:ubiquinone oxidoreductase complex assembly factor 6
• Gene symbol: NDUFAF6
• Synonyms (NCBI Gene): C8orf38, FRTS5, MC1DN17, lncREST
• Chromosome: 8
• Chromosome location: 8q22.1
• Summary: This gene encodes a protein that localizes to mitochondria and contains a predicted phytoene synthase domain. The encoded protein plays an important role in the assembly of complex I (NADH-ubiquinone oxidoreductase) of the mitochondrial respiratory chain

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs137853184	A>G	Pathogenic	Coding sequence variant, genic downstream transcript variant, missense variant, intron variant, 5 prime UTR variant, non coding transcript variant
rs201088736	G>C	Pathogenic	Non coding transcript variant, missense variant, genic downstream transcript variant, coding sequence variant
rs201732170	T>A,C	Pathogenic, uncertain-significance	Non coding transcript variant, 5 prime UTR variant, missense variant, coding sequence variant, genic downstream transcript variant
rs202047755	T>C	Conflicting-interpretations-of-pathogenicity, likely-benign	Non coding transcript variant, synonymous variant, genic downstream transcript variant, coding sequence variant
rs552141388	T>C,G	Likely-pathogenic	Initiator codon variant, genic downstream transcript variant, non coding transcript variant, intron variant, missense variant, 5 prime UTR variant
rs758181982	A>-	Likely-pathogenic	Frameshift variant, genic downstream transcript variant, non coding transcript variant, coding sequence variant, intron variant
rs762093523	A>-,AA	Pathogenic	Genic downstream transcript variant, non coding transcript variant, frameshift variant, coding sequence variant
rs762620949	G>A,T	Likely-pathogenic	Genic downstream transcript variant, non coding transcript variant, missense variant, coding sequence variant
rs765915512	TACTT>-	Likely-pathogenic	Genic downstream transcript variant, non coding transcript variant, frameshift variant, coding sequence variant
rs768273248	C>G,T	Pathogenic	Genic downstream transcript variant, non coding transcript variant, missense variant, coding sequence variant
rs777821109	G>T	Pathogenic	5 prime UTR variant, stop gained, genic downstream transcript variant, non coding transcript variant, coding sequence variant
rs863223931	TC>-	Likely-pathogenic	Genic downstream transcript variant, 5 prime UTR variant, non coding transcript variant, coding sequence variant, frameshift variant
rs863223932	TGCTCCCTGC>-,TGCTCCCTGCTGCTCCCTGC	Likely-pathogenic	Genic downstream transcript variant, 5 prime UTR variant, non coding transcript variant, intron variant, coding sequence variant, frameshift variant
rs1057519084	T>C	Pathogenic	Intron variant, coding sequence variant, missense variant, genic downstream transcript variant, non coding transcript variant, 5 prime UTR variant
rs1057519085	A>T	Pathogenic	Intron variant, coding sequence variant, missense variant, genic downstream transcript variant, non coding transcript variant, 5 prime UTR variant
rs1057519086	A>G	Pathogenic	Intron variant, coding sequence variant, missense variant, genic downstream transcript variant, non coding transcript variant
rs1085307635	C>G	Likely-pathogenic	Genic downstream transcript variant, non coding transcript variant, coding sequence variant, stop gained
rs1131692157	C>T	Pathogenic	Intron variant, coding sequence variant, missense variant, genic downstream transcript variant, non coding transcript variant
rs1224421127	C>G	Likely-pathogenic	Coding sequence variant, genic downstream transcript variant, intron variant, missense variant, non coding transcript variant
rs1463009913	->GT	Likely-pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant, intron variant, genic downstream transcript variant, 5 prime UTR variant
rs1554669910	->T	Pathogenic	Genic downstream transcript variant, splice donor variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT644367	hsa-miR-129-1-3p	HITS-CLIP	23824327
MIRT644366	hsa-miR-129-2-3p	HITS-CLIP	23824327
MIRT644365	hsa-miR-3127-3p	HITS-CLIP	23824327
MIRT644364	hsa-miR-6756-3p	HITS-CLIP	23824327
MIRT644363	hsa-miR-6734-3p	HITS-CLIP	23824327
MIRT644362	hsa-miR-3667-3p	HITS-CLIP	23824327
MIRT644361	hsa-miR-3124-3p	HITS-CLIP	23824327
MIRT644360	hsa-miR-1225-3p	HITS-CLIP	23824327
MIRT644359	hsa-miR-1233-3p	HITS-CLIP	23824327
MIRT644358	hsa-miR-2355-5p	HITS-CLIP	23824327
MIRT644357	hsa-miR-6826-3p	HITS-CLIP	23824327
MIRT644356	hsa-miR-6868-3p	HITS-CLIP	23824327
MIRT644355	hsa-miR-6807-5p	HITS-CLIP	23824327
MIRT644354	hsa-miR-3679-3p	HITS-CLIP	23824327
MIRT644367	hsa-miR-129-1-3p	HITS-CLIP	23824327
MIRT644366	hsa-miR-129-2-3p	HITS-CLIP	23824327
MIRT644365	hsa-miR-3127-3p	HITS-CLIP	23824327
MIRT644364	hsa-miR-6756-3p	HITS-CLIP	23824327
MIRT644363	hsa-miR-6734-3p	HITS-CLIP	23824327
MIRT644362	hsa-miR-3667-3p	HITS-CLIP	23824327
MIRT644361	hsa-miR-3124-3p	HITS-CLIP	23824327
MIRT644360	hsa-miR-1225-3p	HITS-CLIP	23824327
MIRT644359	hsa-miR-1233-3p	HITS-CLIP	23824327
MIRT644358	hsa-miR-2355-5p	HITS-CLIP	23824327
MIRT644357	hsa-miR-6826-3p	HITS-CLIP	23824327
MIRT644356	hsa-miR-6868-3p	HITS-CLIP	23824327
MIRT644355	hsa-miR-6807-5p	HITS-CLIP	23824327
MIRT644354	hsa-miR-3679-3p	HITS-CLIP	23824327

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005515	Function	Protein binding	IPI	32296183
GO:0005634	Component	Nucleus	IDA	22019594
GO:0005634	Component	Nucleus	IEA
GO:0005737	Component	Cytoplasm	IDA	22019594
GO:0005737	Component	Cytoplasm	IEA
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IBA
GO:0005739	Component	Mitochondrion	IEA
GO:0005743	Component	Mitochondrial inner membrane	IDA	22019594
GO:0005743	Component	Mitochondrial inner membrane	IEA
GO:0005743	Component	Mitochondrial inner membrane	TAS
GO:0016020	Component	Membrane	IEA
GO:0032981	Process	Mitochondrial respiratory chain complex I assembly	IBA
GO:0032981	Process	Mitochondrial respiratory chain complex I assembly	IMP	22019594

Other IDs

• MIM: 612392
• HGNC: 28625
• e!Ensembl: ENSG00000156170

Protein

• UniProt ID: Q330K2
• Protein name: NADH dehydrogenase (ubiquinone) complex I, assembly factor 6 (Putative phytoene synthase)
• Protein function: Involved in the assembly of mitochondrial NADH:ubiquinone oxidoreductase complex (complex I) at early stages. May play a role in the biogenesis of complex I subunit MT-ND1.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00494	SQS_PSY	65 → 321		Domain

• Tissue specificity: TISSUE SPECIFICITY: Widely expressed. A lower expression is observed in lung and kidney compared to heart, muscle and liver (PubMed:27466185). In the kidney, expression is high in the basal zone of the proximal tubular cells (PubMed:27466185). {ECO:000026
• Sequence:

  MAASAHGSVWGPLRLGIPGLCCRRPPLGLYARMRRLPGPEVSGRSVAAASGPGAWGTDHY
  CLELLRKRDYEGYLCSLLLPAESRSSVFALRAFNVELAQVKDSVSEKTIGLMRMQFWKKT
  VEDIYCDNPPHQPVAIELWKAVKRHNLTKRWLMKIVDEREKNLDDKAYRNIKELENYAEN
  TQSSLLYLTLEILGIKDLHADHAASHIGKAQGIVTCLRATPYHGSRRKVFLPMDICMLHG
  VSQEDFLRRNQDKNVRDVIYDIASQAHLHLKHARSFHKTVPVKAFPAFLQTVSLEDFLKK
  IQRVDFDIFHPSLQQKNTLLPLYLYIQSWRKTY

• Sequence length: 333

Pathways

KEGG:

Thermogenesis

Reactome:

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
Developmental regression	Likely pathogenic	rs1224421127	RCV000627000	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Familial prostate cancer	Likely pathogenic; Pathogenic	rs753873681	RCV005909194	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Fanconi renotubular syndrome 5	Likely pathogenic; Pathogenic	rs762093523, rs777821109	RCV005050359 RCV005355998	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Leigh syndrome	Likely pathogenic; Pathogenic	rs762620949, rs753873681	RCV000626222 RCV001249207	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Mitochondrial complex I deficiency, nuclear type 17	Likely pathogenic; Pathogenic	rs1829405389, rs1829405956, rs762093523, rs137853184, rs768273248, rs1057519084, rs1057519085, rs777821109, rs765915512, rs749738738, rs1179490149, rs753873681	RCV001330427 RCV001374467 RCV001374720 RCV000000577 RCV000412599 RCV000412495 RCV000412636 RCV005355998 RCV004800487 RCV001194668 RCV001194669 RCV003152754	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ANDROGENETIC ALOPECIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARDIOVASCULAR DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon adenocarcinoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CORONARY ARTERY DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DE TONI-DEBRE-FANCONI SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GOUT	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERTENSION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
KERATOCONUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LATE-ONSET ALZHEIMER'S DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LEIGH SYNDROME WITH LEUKODYSTROPHY	—	GenCC	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
METABOLIC SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mitochondrial complex I deficiency	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mitochondrial disease	Conflicting classifications of pathogenicity	ClinVar ClinGen, Orphanet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
MITOCHONDRIAL DISEASES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MYOCARDIAL INFARCTION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NDUFAF6-related disorder	Uncertain significance; Benign; Conflicting classifications of pathogenicity; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NON-ALCOHOLIC FATTY LIVER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nonpapillary renal cell carcinoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian cancer	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PERIPHERAL NEUROPATHY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PRIMARY FANCONI RENOTUBULAR SYNDROME	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PRIMARY FANCONI SYNDROME	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PSORIASIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
UPPER AERODIGESTIVE TRACT NEOPLASM	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
VESICOURETERAL REFLUX	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Alzheimer Disease	Alzheimer disease	Pubtator	31473137, 35237031, 35699875, 35715361	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Alzheimer`s Disease	Alzheimer disease	GWASDB_DG	24162737		★☆☆☆☆ Found in Text Mining only
Alzheimer`s Disease	Alzheimer disease	GWASCAT_DG	24162737, 31473137		★☆☆☆☆ Found in Text Mining only
Anemia	Anemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Blepharoptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	37950222	Associate	★☆☆☆☆ Found in Text Mining only
Cardiovascular Diseases	Cardiovascular Diseases	GWASCAT_DG	30595370		★☆☆☆☆ Found in Text Mining only
Cerebral Small Vessel Diseases	Cerebral microangiopathy	Pubtator	35699875	Associate	★☆☆☆☆ Found in Text Mining only
Childhood Onset Dystonias	Dystonia	BEFREE	30642748		★☆☆☆☆ Found in Text Mining only
De Toni-Debre-Fanconi Syndrome	Fanconi Syndrome	BEFREE	27466185		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Developmental regression	Developmental regression	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	GWASCAT_DG	20581827, 24509480, 30054458, 30595370		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	GWASDB_DG	20581827, 21647700, 23300278, 24509480		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	BEFREE	28870582		★☆☆☆☆ Found in Text Mining only
Dysarthria	Dysarthria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dystonia Disorders	Dystonia	BEFREE	30642748		★☆☆☆☆ Found in Text Mining only
Fanconi Anemia	Fanconi Anemia	BEFREE	27466185		★☆☆☆☆ Found in Text Mining only
Fanconi Syndrome	Fanconi Syndrome	BEFREE	27466185		★☆☆☆☆ 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
Leigh Disease	Leigh Syndrome	GENOMICS_ENGLAND_DG	18614015, 26741492, 27604308		★☆☆☆☆ Found in Text Mining only
Leigh Disease	Leigh Syndrome	BEFREE	22019594, 23509070, 29531337, 30642748		★☆☆☆☆ Found in Text Mining only
Leigh Disease	Leigh syndrome	Pubtator	29531337, 31967322, 33097395, 36675121	Associate	★☆☆☆☆ 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	GENOMICS_ENGLAND_DG	26741492		★☆☆☆☆ 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
MELAS Syndrome	Melas syndrome	Pubtator	35699875	Associate	★☆☆☆☆ Found in Text Mining only
Mitochondrial complex I deficiency	Mitochondrial complex deficiency	Pubtator	19463981, 29531337	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MITOCHONDRIAL COMPLEX I DEFICIENCY	Mitochondrial Complex Deficiency	BEFREE	29531337		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MITOCHONDRIAL COMPLEX I DEFICIENCY, NUCLEAR TYPE 17	Mitochondrial Complex Deficiency	UNIPROT_DG	18614015, 22019594, 26741492		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
MITOCHONDRIAL COMPLEX I DEFICIENCY, NUCLEAR TYPE 17	Mitochondrial Complex Deficiency	CLINVAR_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Mood swings	Mood swings	HPO_DG			★☆☆☆☆ Found in Text Mining only
Movement Disorders	Movement Disorders	CLINVAR_DG	18614015, 26741492, 27466185		★☆☆☆☆ Found in Text Mining only
Neuropathy	Neuropathy	GWASCAT_DG	25710658		★☆☆☆☆ 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
Peripheral Nervous System Diseases	Nervous System Diseases	GWASCAT_DG	25710658		★☆☆☆☆ Found in Text Mining only
Peripheral Nervous System Diseases	Nervous System Diseases	HPO_DG			★☆☆☆☆ Found in Text Mining only
Precursor Cell Lymphoblastic Leukemia Lymphoma	Lymphoblastic Leukemia	GWASCAT_DG	25710658		★☆☆☆☆ Found in Text Mining only
Primary Fanconi renotubular syndrome	Fanconi Syndrome	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
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
Scoliosis, unspecified	Scoliosis	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