NDUFA2

NADH:ubiquinone oxidoreductase subunit A2, the group of NADH:ubiquinone oxidoreductase supernumerary subunits

Basic information

Region (hg38): 5:140638740-140647771

Links

ENSG00000131495 ∙ NCBI:4695 ∙ OMIM:602137 ∙ HGNC:7685 ∙ Uniprot:O43678 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cystic leukoencephalopathy without megalencephaly (Supportive), mode of inheritance: AR
• Leigh syndrome with leukodystrophy (Supportive), mode of inheritance: AR
• mitochondrial complex I deficiency, nuclear type 13 (Strong), mode of inheritance: AR
• Leigh syndrome (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial complex I deficiency, nuclear type 13; Leigh syndrome	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; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic	11743516; 18513682
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 NDUFA2 gene.

• not_provided (45 variants)
• Inborn_genetic_diseases (14 variants)
• not_specified (6 variants)
• Mitochondrial_complex_I_deficiency,_nuclear_type_13 (6 variants)
• NDUFA2-related_disorder (6 variants)
• Mitochondrial_complex_I_deficiency,_nuclear_type_1 (5 variants)
• Cystic_Leukoencephalopathy (2 variants)
• Leigh_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NDUFA2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000002488.5. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	11	2	14
missense	2		25	3		30
nonsense						0
start loss						0
frameshift		1	2			3
splice donor/acceptor (+/-2bp)						0
Total	2	1	28	14	2

Highest pathogenic variant AF is 0.0000065706477

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NDUFA2	protein_coding	protein_coding	ENST00000252102	3	9046

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.774	0.220	125740	0	1	125741	0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.240	62	56.9	1.09	0.00000279	629
Missense in Polyphen		14	13.841	1.0115		168
Synonymous	-0.723	29	24.4	1.19	0.00000129	200
Loss of Function	2.05	0	4.92	0.00	2.12e-7	52

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	0.0000462	0.0000462
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;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: 0.181

Intolerance Scores

• loftool: 0.308
• rvis_EVS: 0.19
• rvis_percentile_EVS: 66.57

Haploinsufficiency Scores

• pHI: 0.320
• hipred: N
• hipred_score: 0.432
• ghis: 0.454

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0104

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ndufa2

Gene ontology

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