NDUFA6

NADH:ubiquinone oxidoreductase subunit A6, the group of NADH:ubiquinone oxidoreductase supernumerary subunits|LYR motif containing

Basic information

Region (hg38): 22:42085526-42090884

Links

ENSG00000184983 ∙ NCBI:4700 ∙ OMIM:602138 ∙ HGNC:7690 ∙ Uniprot:P56556 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial complex 1 deficiency, nuclear type 33 (Moderate), mode of inheritance: AR
• mitochondrial complex I deficiency (Supportive), mode of inheritance: AR
• mitochondrial complex 1 deficiency, nuclear type 33 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Medical treatment (eg, riboflavin, ubiquinol) may be beneficial; Individuals may have cardiac involvement	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Neurologic; Ophthalmologic	30245030
Medical treatment (eg, riboflavin, uniquinol) may be beneficial; Individuals may have cardiac involvement

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NDUFA6 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NDUFA6 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				14		14
missense			25	1	1	27
nonsense			1			1
start loss						0
frameshift		1	1			2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			2			2
non coding			1	4	2	7
Total	0	1	28	19	3

Variants in NDUFA6

This is a list of pathogenic ClinVar variants found in the NDUFA6 region.

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

Position	Type	Phenotype	Significance	ClinVar
22-42086183-T-G		Mitochondrial complex 1 deficiency, nuclear type 33	Uncertain significance (May 12, 2020)
22-42086192-G-A		NDUFA6-related disorder	Benign/Likely benign (Jul 01, 2024)
22-42086195-G-T			Likely benign (Apr 06, 2023)
22-42086202-T-C			Uncertain significance (Aug 21, 2022)
22-42086205-A-G			Uncertain significance (Aug 20, 2022)
22-42086209-T-C			Uncertain significance (Jun 19, 2023)
22-42086214-AG-A		Mitochondrial disease • Mitochondrial complex 1 deficiency, nuclear type 33	Pathogenic (Dec 13, 2018)
22-42086234-C-T			Likely benign (Nov 13, 2023)
22-42086235-G-A			Uncertain significance (Oct 04, 2022)
22-42086237-TTC-T		Mitochondrial complex 1 deficiency, nuclear type 33 • Mitochondrial disease	Pathogenic (Dec 13, 2018)
22-42086248-G-A		not specified	Benign/Likely benign (Jan 20, 2024)
22-42086249-G-A			Likely benign (Mar 20, 2023)
22-42086255-C-A			Likely benign (Oct 13, 2023)
22-42086256-C-T		Inborn genetic diseases	Uncertain significance (Aug 12, 2021)
22-42086260-TA-T		Mitochondrial disease • Mitochondrial complex 1 deficiency, nuclear type 33 • Inborn genetic diseases • NDUFA6-related disorder	Likely pathogenic (Jan 20, 2022)
22-42086263-CAT-C			Uncertain significance (Oct 03, 2023)
22-42086271-C-T		Inborn genetic diseases	Uncertain significance (Oct 05, 2022)
22-42086285-TTTAA-T		Inborn genetic diseases	Conflicting classifications of pathogenicity (Sep 12, 2022)
22-42086300-C-T			Likely benign (Dec 05, 2023)
22-42086305-C-A		Mitochondrial complex 1 deficiency, nuclear type 33 • Mitochondrial disease	Pathogenic (Dec 13, 2018)
22-42086306-G-A			Likely benign (Sep 07, 2022)
22-42086329-G-A			Likely benign (Jul 15, 2022)
22-42086498-C-G			Benign (May 13, 2021)
22-42087042-T-G			Benign (Jan 22, 2024)
22-42087050-G-A			Likely benign (Jun 07, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NDUFA6	protein_coding	protein_coding	ENST00000498737	3	5431

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000132	0.419	125688	0	60	125748	0.000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.799	111	89.7	1.24	0.00000513	1016
Missense in Polyphen		30	28.806	1.0415		324
Synonymous	-2.70	53	33.2	1.60	0.00000176	301
Loss of Function	0.168	6	6.46	0.929	3.66e-7	67

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000260	0.000260
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000317	0.000316
Middle Eastern	0.0000544	0.0000544
South Asian	0.000294	0.000294
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed to be not involved in 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. {ECO:0000269|PubMed:27626371}.
• Pathway: Retrograde endocannabinoid signaling - Homo sapiens (human);Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human);Alzheimer,s disease - Homo sapiens (human);Huntington,s disease - Homo sapiens (human);Thermogenesis - Homo sapiens (human);Oxidative phosphorylation - Homo sapiens (human);Parkinson,s disease - Homo sapiens (human);Electron Transport Chain;Oxidative phosphorylation;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: 0.336

Intolerance Scores

• loftool: 0.825
• rvis_EVS: 0.46
• rvis_percentile_EVS: 78.28

Haploinsufficiency Scores

• pHI: 0.0957
• hipred: N
• hipred_score: 0.208
• ghis: 0.512

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.942

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ndufa6

Gene ontology

• Biological process: mitochondrial electron transport, NADH to ubiquinone;response to oxidative stress;mitochondrial respiratory chain complex I assembly
• Cellular component: mitochondrial inner membrane;mitochondrial respiratory chain complex I;mitochondrial membrane
• Molecular function: NADH dehydrogenase (ubiquinone) activity