NDUFA12

NADH:ubiquinone oxidoreductase subunit A12, the group of NADH:ubiquinone oxidoreductase supernumerary subunits

Basic information

Region (hg38): 12:94895297-95003748

Links

ENSG00000184752 ∙ NCBI:55967 ∙ OMIM:614530 ∙ HGNC:23987 ∙ Uniprot:Q9UI09 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial complex I deficiency, nuclear type 23 (Moderate), mode of inheritance: AR
• Leigh syndrome with leukodystrophy (Supportive), mode of inheritance: AR
• mitochondrial complex I deficiency, nuclear type 23 (Strong), mode of inheritance: AR
• mitochondrial complex I deficiency, nuclear type 23 (Definitive), mode of inheritance: AR
• Leigh syndrome (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial complex I deficiency, nuclear type 23; 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	21617257; 33715266; 35141356
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 NDUFA12 gene.

• not_provided (55 variants)
• Inborn_genetic_diseases (20 variants)
• Mitochondrial_complex_I_deficiency,_nuclear_type_23 (13 variants)
• not_specified (8 variants)
• Leigh_syndrome (3 variants)
• NDUFA12-related_disorder (2 variants)
• SLC35A2-congenital_disorder_of_glycosylation (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NDUFA12 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000018838.5. 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	13	1	15
missense	1		35	3		39
nonsense	3	3				6
start loss		1				1
frameshift	4	1	3			8
splice donor/acceptor (+/-2bp)		1				1
Total	8	6	39	16	1

Highest pathogenic variant AF is 0.0000458541

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NDUFA12	protein_coding	protein_coding	ENST00000327772	4	106716

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000743	0.527	125721	0	26	125747	0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.00353	83	83.1	0.999	0.00000456	947
Missense in Polyphen		22	27.002	0.81475		363
Synonymous	-0.921	36	29.6	1.22	0.00000155	273
Loss of Function	0.536	7	8.71	0.804	4.62e-7	88

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000358	0.000358
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.000323	0.000323
European (Non-Finnish)	0.0000528	0.0000527
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000980	0.0000980
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}.
• Disease: DISEASE: Leigh syndrome (LS) [MIM:256000]: An early-onset progressive neurodegenerative disorder characterized by the presence of focal, bilateral lesions in one or more areas of the central nervous system including the brainstem, thalamus, basal ganglia, cerebellum and spinal cord. Clinical features depend on which areas of the central nervous system are involved and include subacute onset of psychomotor retardation, hypotonia, ataxia, weakness, vision loss, eye movement abnormalities, seizures, and dysphagia. {ECO:0000269|PubMed:21617257}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• 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;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: 0.112

Intolerance Scores

• loftool: 0.759
• rvis_EVS: -0.1
• rvis_percentile_EVS: 46.2

Haploinsufficiency Scores

• pHI: 0.0939
• hipred: N
• hipred_score: 0.218
• ghis: 0.612

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.845

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ndufa12

Gene ontology

• Biological process: response to oxidative stress;respiratory gaseous exchange;mitochondrial respiratory chain complex I assembly;mitochondrial ATP synthesis coupled electron transport
• Cellular component: mitochondrion;mitochondrial inner membrane;mitochondrial respiratory chain complex I;cytosol
• Molecular function: NADH dehydrogenase (ubiquinone) activity;electron transfer activity