NDUFA9

NADH:ubiquinone oxidoreductase subunit A9, the group of NADH:ubiquinone oxidoreductase supernumerary subunits|Short chain dehydrogenase/reductase superfamily

Basic information

Region (hg38): 12:4649094-4694317

Previous symbols: [ "NDUFS2L" ]

Links

ENSG00000139180 ∙ NCBI:4704 ∙ OMIM:603834 ∙ HGNC:7693 ∙ Uniprot:Q16795 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Leigh syndrome (Limited), mode of inheritance: AR
• Leigh syndrome with leukodystrophy (Supportive), mode of inheritance: AR
• mitochondrial complex 1 deficiency, nuclear type 26 (Limited), 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 26; 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	22114105
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 NDUFA9 gene.

• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NDUFA9 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				29	1	30
missense		1	75	6	3	85
nonsense	1	2	1			4
start loss						0
frameshift			2			2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			6	3		9
non coding			1	22	36	59
Total	1	3	79	57	40

Highest pathogenic variant AF is 0.00000657

Variants in NDUFA9

This is a list of pathogenic ClinVar variants found in the NDUFA9 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-4649133-G-A			Uncertain significance (Dec 02, 2021)
12-4649134-C-T			Uncertain significance (Dec 03, 2021)
12-4649138-C-T			Likely benign (Jul 12, 2022)
12-4649139-G-C		not specified	Benign (Jan 22, 2024)
12-4649140-C-T		Inborn genetic diseases	Likely benign (Dec 08, 2023)
12-4649145-T-G			Uncertain significance (Oct 17, 2023)
12-4649145-T-AC			Uncertain significance (Jul 05, 2022)
12-4649148-C-T		Inborn genetic diseases	Uncertain significance (Dec 20, 2021)
12-4649153-T-C			Likely benign (Apr 05, 2018)
12-4649157-C-T		not specified	Conflicting classifications of pathogenicity (Oct 13, 2022)
12-4649181-T-C			Uncertain significance (Jul 21, 2021)
12-4653991-A-G			Benign (Jun 14, 2018)
12-4654031-G-C			Likely benign (Jul 27, 2018)
12-4654042-A-G			Likely benign (May 20, 2020)
12-4654183-C-T			Benign (Jun 23, 2018)
12-4654234-G-C			Benign (Jun 23, 2018)
12-4654238-G-C			Benign (Jun 19, 2018)
12-4654281-TTTTG-T			Uncertain significance (May 23, 2023)
12-4654292-G-T		Mitochondrial complex 1 deficiency, nuclear type 26	Uncertain significance (May 01, 2020)
12-4654300-A-G		not specified	Conflicting classifications of pathogenicity (Nov 29, 2022)
12-4654310-T-C		Inborn genetic diseases	Uncertain significance (Jun 22, 2021)
12-4654329-C-T			Likely benign (Apr 20, 2022)
12-4654330-G-A			Uncertain significance (Jun 15, 2022)
12-4654336-C-A			Uncertain significance (Jun 03, 2023)
12-4654364-T-C			Uncertain significance (Jul 29, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NDUFA9	protein_coding	protein_coding	ENST00000266544	11	40194

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00480	0.994	125721	0	26	125747	0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0866	226	230	0.984	0.0000132	2441
Missense in Polyphen		53	64.659	0.81969		753
Synonymous	-0.280	84	80.8	1.04	0.00000448	752
Loss of Function	2.84	8	22.6	0.355	0.00000140	231

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000212	0.000211
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000125	0.000123
Middle Eastern	0.000109	0.000109
South Asian	0.0000982	0.0000980
Other	0.000339	0.000326

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:22114105, 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:22114105}. 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;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: 0.170

Intolerance Scores

• loftool: 0.314
• rvis_EVS: 0.31
• rvis_percentile_EVS: 72.6

Haploinsufficiency Scores

• pHI: 0.166
• hipred: N
• hipred_score: 0.377
• ghis: 0.493

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.978

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ndufa9

Gene ontology

• Biological process: mitochondrial electron transport, NADH to ubiquinone;sodium ion transport;circadian rhythm;response to glucose;mitochondrial respiratory chain complex I assembly;ubiquinone-6 biosynthetic process
• Cellular component: nucleus;nucleoplasm;mitochondrion;mitochondrial respiratory chain complex I;mitochondrial matrix;mitochondrial membrane
• Molecular function: NADH dehydrogenase activity;protein binding;NADH dehydrogenase (ubiquinone) activity;protein-containing complex binding;coenzyme binding