NDUFA8
NADH:ubiquinone oxidoreductase subunit A8, the group of NADH:ubiquinone oxidoreductase supernumerary subunits
Basic information
Region (hg38): 9:122144058-122159779
Links
Phenotypes
GenCC
Source:
- mitochondrial complex 1 deficiency, nuclear type 37 (Limited), mode of inheritance: Unknown
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Mitochondrial complex I deficiency, nuclear type 37 | 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 | 32385911; 33153867 |
| Medical treatment (eg, riboflavin, ubiquinol) may be beneficial; Individuals may have cardiac involvement |
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the NDUFA8 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 | 0 | |||||
| missense | 13 | 13 | ||||
| nonsense | 1 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 1 | 13 | 0 | 0 |
Variants in NDUFA8
This is a list of pathogenic ClinVar variants found in the NDUFA8 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 9-122144293-C-G | not specified | Uncertain significance (Dec 26, 2023) | ||
| 9-122144357-G-A | Mitochondrial complex 1 deficiency, nuclear type 37 | Likely pathogenic (Aug 01, 2021) | ||
| 9-122144359-T-C | not specified | Uncertain significance (Aug 10, 2021) | ||
| 9-122148141-C-G | not specified | Uncertain significance (Dec 09, 2023) | ||
| 9-122148200-C-A | Mitochondrial complex 1 deficiency, nuclear type 37 | Pathogenic (Apr 15, 2021) | ||
| 9-122148264-G-C | not specified | Uncertain significance (Nov 18, 2022) | ||
| 9-122148266-C-T | not specified | Uncertain significance (Jun 29, 2023) | ||
| 9-122148267-G-A | not specified | Uncertain significance (Feb 05, 2024) | ||
| 9-122152278-T-C | not specified | Uncertain significance (May 11, 2022) | ||
| 9-122152296-C-T | Mitochondrial complex 1 deficiency, nuclear type 37 | Uncertain significance (Jun 19, 2023) | ||
| 9-122152320-C-T | not specified | Uncertain significance (Apr 27, 2023) | ||
| 9-122152321-G-A | Mitochondrial complex 1 deficiency, nuclear type 37 | Pathogenic (Apr 16, 2021) | ||
| 9-122152330-T-C | Mitochondrial complex 1 deficiency, nuclear type 37 | Uncertain significance (Oct 16, 2023) | ||
| 9-122152365-T-C | Mitochondrial complex 1 deficiency, nuclear type 37 • not specified | Uncertain significance (Jun 19, 2024) | ||
| 9-122152367-G-C | not specified | Uncertain significance (Mar 31, 2024) | ||
| 9-122152386-A-G | not specified | Uncertain significance (Mar 29, 2024) | ||
| 9-122159641-G-C | not specified | Uncertain significance (Jun 22, 2023) | ||
| 9-122159666-T-C | not specified | Uncertain significance (Feb 16, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| NDUFA8 | protein_coding | protein_coding | ENST00000373768 | 4 | 27354 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.344 | 0.644 | 125718 | 0 | 28 | 125746 | 0.000111 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.481 | 86 | 99.5 | 0.864 | 0.00000617 | 1126 |
| Missense in Polyphen | 26 | 27.622 | 0.94128 | 288 | ||
| Synonymous | 0.634 | 31 | 35.8 | 0.865 | 0.00000209 | 319 |
| Loss of Function | 2.10 | 2 | 8.70 | 0.230 | 4.40e-7 | 109 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000904 | 0.0000904 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.000231 | 0.000229 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- 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);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
- 0.226
Intolerance Scores
- loftool
- 0.381
- rvis_EVS
- -0.23
- rvis_percentile_EVS
- 36.86
Haploinsufficiency Scores
- pHI
- 0.416
- hipred
- N
- hipred_score
- 0.267
- ghis
- 0.577
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- H
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.721
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Ndufa8
- 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); vision/eye phenotype; 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;mitochondrial intermembrane space
- Molecular function
- NADH dehydrogenase (ubiquinone) activity;protein-containing complex binding