NDUFAF6

NADH:ubiquinone oxidoreductase complex assembly factor 6, the group of Mitochondrial respiratory chain complex assembly factors|MicroRNA protein coding host genes

Basic information

Region (hg38): 8:94895532-95116455

Previous symbols: [ "C8orf38" ]

Links

ENSG00000156170 ∙ NCBI:137682 ∙ OMIM:612392 ∙ HGNC:28625 ∙ Uniprot:Q330K2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial complex 1 deficiency, nuclear type 17 (Moderate), mode of inheritance: AR
• Fanconi renotubular syndrome 5 (Limited), mode of inheritance: AR
• primary Fanconi syndrome (Supportive), mode of inheritance: AD
• Leigh syndrome with leukodystrophy (Supportive), mode of inheritance: AR
• Leigh syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Fanconi renotubular syndrome 5	AR	Renal	Individuals with Fanconi renotubular syndrome may have renal tubular disease, and medical management (eg, correction of acidosis, phosphate, and vitamin D levels) has been shown to be beneficial; Renal transplant has been described	Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic; Pulmonary; Renal	17690917; 18614015; 27466185
In Mitochondrial complex I deficiency, nuclear type 17, medical treatment (eg, riboflavin, ubiquinol) may be beneficial; Individuals may have cardiac involvement

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NDUFAF6 gene.

• not provided (179 variants)
• Inborn genetic diseases (25 variants)
• not specified (23 variants)
• Mitochondrial complex 1 deficiency, nuclear type 17 (18 variants)
• Leigh syndrome (8 variants)
• Mitochondrial complex 1 deficiency, nuclear type 17;Fanconi renotubular syndrome 5 (4 variants)
• Fanconi renotubular syndrome 5 (4 variants)
• Developmental regression (2 variants)
• - (2 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NDUFAF6 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	26	4	31
missense		2	74	5		81
nonsense	2	3	1			6
start loss	1	1				2
frameshift	4	5	2			11
inframe indel			2			2
splice donor/acceptor (+/-2bp)						0
splice region	1	1	2	5	1	10
non coding	1		1	30	33	65
Total	8	11	81	61	37

Highest pathogenic variant AF is 0.0000394

Variants in NDUFAF6

This is a list of pathogenic ClinVar variants found in the NDUFAF6 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-94930489-T-C		not specified	Uncertain significance (Oct 06, 2022)
8-94930495-C-T		not specified	Uncertain significance (Nov 12, 2021)
8-94930532-T-G		not specified	Uncertain significance (Dec 11, 2023)
8-94930570-C-T		not specified	Uncertain significance (Dec 08, 2023)
8-94930571-G-A		not specified	Uncertain significance (Mar 01, 2023)
8-94930573-C-G		not specified	Uncertain significance (Nov 21, 2023)
8-94930578-G-C		not specified	Uncertain significance (Dec 19, 2022)
8-94930594-G-A		not specified	Uncertain significance (Oct 25, 2023)
8-94930633-C-T		not specified	Uncertain significance (Dec 08, 2023)
8-94930699-T-C		not specified	Uncertain significance (Jul 08, 2022)
8-94939938-T-C		not specified	Uncertain significance (May 27, 2022)
8-94940019-G-A		not specified	Uncertain significance (Nov 15, 2021)
8-94940029-G-A		not specified	Uncertain significance (Jul 12, 2023)
8-94940029-G-C		not specified	Uncertain significance (Apr 12, 2023)
8-94940038-T-C		not specified	Uncertain significance (Sep 14, 2021)
8-94940109-C-A		not specified	Uncertain significance (Apr 07, 2023)
8-94940124-G-A		not specified	Uncertain significance (Oct 27, 2022)
8-94940158-G-A		not specified	Uncertain significance (Sep 14, 2022)
8-94940871-T-C		not specified	Likely benign (Jul 19, 2023)
8-94940888-G-C		not specified	Uncertain significance (Dec 19, 2023)
8-95024928-A-G			Benign (Jun 26, 2018)
8-95024960-T-G		not specified	Likely benign (Nov 08, 2017)
8-95024978-G-T		not specified	Benign (Feb 04, 2014)
8-95024984-T-C		not specified	Likely benign (Mar 29, 2016)
8-95025004-G-T			Likely benign (May 03, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NDUFAF6	protein_coding	protein_coding	ENST00000396124	9	220689

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.07e-8	0.521	125624	0	124	125748	0.000493

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.572	142	163	0.874	0.00000805	2125
Missense in Polyphen		37	49.099	0.75358		603
Synonymous	1.09	48	58.6	0.820	0.00000273	640
Loss of Function	0.950	13	17.3	0.753	9.83e-7	199

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000539	0.000536
Ashkenazi Jewish	0.00	0.00
East Asian	0.000340	0.000326
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000556	0.000554
Middle Eastern	0.000340	0.000326
South Asian	0.00108	0.00108
Other	0.000820	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the assembly of mitochondrial NADH:ubiquinone oxidoreductase complex (complex I) at early stages. May play a role in the biogenesis of MT-ND1. {ECO:0000269|PubMed:18614015, ECO:0000269|PubMed:22019594}.
• Disease: DISEASE: Mitochondrial complex I deficiency (MT-C1D) [MIM:252010]: A disorder of the mitochondrial respiratory chain that causes a wide range of clinical manifestations 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. {ECO:0000269|PubMed:18614015, ECO:0000269|PubMed:22019594, ECO:0000269|PubMed:26741492}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Thermogenesis - Homo sapiens (human);Respiratory electron transport;The citric acid (TCA) cycle and respiratory electron transport;Metabolism;Complex I biogenesis;Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. (Consensus)

Recessive Scores

• pRec: 0.0983

Intolerance Scores

• rvis_EVS: -0.16
• rvis_percentile_EVS: 41.64

Haploinsufficiency Scores

• pHI: 0.108
• hipred: N
• hipred_score: 0.229
• ghis: 0.562

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ndufaf6
• Phenotype: growth/size/body region phenotype

Gene ontology

• Biological process: mitochondrial respiratory chain complex I assembly
• Cellular component: nucleus;mitochondrion;mitochondrial inner membrane