NDUFA1

NADH:ubiquinone oxidoreductase subunit A1, the group of NADH:ubiquinone oxidoreductase supernumerary subunits

Basic information

Region (hg38): X:119871831-119876662

Links

ENSG00000125356 ∙ NCBI:4694 ∙ OMIM:300078 ∙ HGNC:7683 ∙ Uniprot:O15239 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial complex I deficiency, nuclear type (Definitive), mode of inheritance: XLR
• mitochondrial complex 1 deficiency, nuclear type 12 (Moderate), mode of inheritance: AR
• mitochondrial complex 1 deficiency, nuclear type 12 (Strong), mode of inheritance: XL
• mitochondrial complex I deficiency (Supportive), mode of inheritance: AR
• mitochondrial complex I deficiency, nuclear type 1 (Definitive), mode of inheritance: XL
• Leigh syndrome (Moderate), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial complex I deficiency, nuclear type 12	XL	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; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic	11743516; 17262856; 21596602
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 NDUFA1 gene.

• not provided (31 variants)
• not specified (6 variants)
• Inborn genetic diseases (5 variants)
• Mitochondrial complex 1 deficiency, nuclear type 12 (2 variants)
• Mitochondrial complex I deficiency (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NDUFA1 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				5		5
missense		1	6	1		8
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1	2	3
non coding				6	13	19
Total	0	1	7	12	13

Variants in NDUFA1

This is a list of pathogenic ClinVar variants found in the NDUFA1 region.

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

Position	Type	Phenotype	Significance	ClinVar
X-119871868-C-G		not specified	Likely benign (Oct 02, 2017)
X-119871879-A-C		not specified	Benign (Apr 09, 2015)
X-119871908-A-G		not specified • Inborn genetic diseases	Benign (Mar 05, 2019)
X-119871927-C-T		NDUFA1-related disorder	Uncertain significance (Oct 21, 2023)
X-119871933-G-C		Mitochondrial complex 1 deficiency, nuclear type 12	Pathogenic (Jan 01, 2007)
X-119871946-T-C			Uncertain significance (Nov 27, 2021)
X-119871950-C-T			Likely benign (Aug 21, 2022)
X-119871956-C-T		Inborn genetic diseases	Likely benign (Oct 20, 2017)
X-119871979-CTGCG-C			Uncertain significance (Jul 02, 2020)
X-119871988-T-C			Uncertain significance (Dec 22, 2022)
X-119871995-G-A			Likely benign (Jul 01, 2023)
X-119872005-G-C		Mitochondrial complex I deficiency • not specified • Mitochondrial complex 1 deficiency, nuclear type 12 • Inborn genetic diseases • NDUFA1-related disorder	Benign/Likely benign (Jan 16, 2024)
X-119872018-G-A			Benign (Apr 03, 2022)
X-119872020-C-T			Likely benign (Oct 03, 2023)
X-119872026-C-T			Benign (Sep 06, 2022)
X-119872030-C-T		not specified	Likely benign (Jul 19, 2022)
X-119872032-G-A			Likely benign (Jul 04, 2022)
X-119873028-A-G			Benign (Jun 28, 2018)
X-119873045-C-CT			Likely benign (Aug 26, 2019)
X-119873060-T-A			Benign (Aug 13, 2019)
X-119873060-TA-T			Likely benign (Aug 18, 2019)
X-119873060-T-TA			Benign (Aug 10, 2019)
X-119873061-A-T			Benign (Aug 26, 2019)
X-119873071-GA-G			Likely benign (May 18, 2020)
X-119873080-T-C			Benign (Jun 14, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NDUFA1	protein_coding	protein_coding	ENST00000371437	3	5176

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.553	0.399	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.963	14	28.5	0.492	0.00000212	453
Missense in Polyphen		6	11.284	0.53171		214
Synonymous	0.197	9	9.78	0.920	6.53e-7	130
Loss of Function	1.44	0	2.42	0.00	1.53e-7	41

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be 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);Metformin Pathway, Pharmacodynamic;Mitochondrial Electron Transport Chain;Electron Transport Chain;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: 0.00102

Intolerance Scores

• rvis_EVS: 0.28
• rvis_percentile_EVS: 70.87

Haploinsufficiency Scores

• pHI: 0.000840
• hipred: N
• hipred_score: 0.303
• ghis: 0.400

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: H
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ndufa1
• Phenotype: liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); homeostasis/metabolism phenotype

Gene ontology

• Biological process: mitochondrial electron transport, NADH to ubiquinone;mitochondrial respiratory chain complex I assembly
• Cellular component: mitochondrion;mitochondrial inner membrane;mitochondrial respiratory chain complex I;cytosol;integral component of membrane;mitochondrial membrane
• Molecular function: NADH dehydrogenase (ubiquinone) activity