NDUFAF4
Basic information
Region (hg38): 6:96889315-96897891
Previous symbols: [ "C6orf66" ]
Links
Phenotypes
GenCC
Source:
- mitochondrial complex I deficiency, nuclear type 15 (Strong), mode of inheritance: AR
- mitochondrial complex I deficiency (Supportive), mode of inheritance: AR
- Leigh syndrome (Limited), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Mitochondrial complex I deficiency, nuclear type 15 | 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; 18179882 |
| Medical treatment (eg, riboflavin, ubiquinol) may be beneficial; Individuals may have cardiac involvement |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (42 variants)
- Inborn_genetic_diseases (19 variants)
- Mitochondrial_complex_I_deficiency,_nuclear_type_1 (12 variants)
- not_specified (7 variants)
- Mitochondrial_complex_I_deficiency,_nuclear_type_15 (5 variants)
- NDUFAF4-related_disorder (1 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 NDUFAF4 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000014165.4. 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 | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 10 | 13 | ||||
| missense | 31 | 40 | ||||
| nonsense | 0 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 1 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 1 | 2 | 35 | 15 | 2 |
Highest pathogenic variant AF is 0.0000013681594
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| NDUFAF4 | protein_coding | protein_coding | ENST00000316149 | 3 | 8569 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.553 | 0.435 | 125744 | 0 | 4 | 125748 | 0.0000159 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.0626 | 90 | 91.7 | 0.982 | 0.00000451 | 1154 |
| Missense in Polyphen | 24 | 26.49 | 0.90602 | 337 | ||
| Synonymous | -0.383 | 37 | 34.2 | 1.08 | 0.00000176 | 324 |
| Loss of Function | 2.02 | 1 | 6.61 | 0.151 | 2.91e-7 | 80 |
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) | 0.0000352 | 0.0000352 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Involved in the assembly of mitochondrial NADH:ubiquinone oxidoreductase complex (complex I). May be involved in cell proliferation and survival of hormone-dependent tumor cells. May be a regulator of breast tumor cell invasion. {ECO:0000269|PubMed:14871833, ECO:0000269|PubMed:17001319, ECO:0000269|PubMed:18179882}.;
- Disease
- DISEASE: Mitochondrial complex I deficiency (MT-C1D) [MIM:252010]: A disorder of the mitochondrial respiratory chain that causes a wide range of clinical manifestations from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. {ECO:0000269|PubMed:18179882}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Thermogenesis - Homo sapiens (human);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
- 0.0942
Intolerance Scores
- loftool
- 0.198
- rvis_EVS
- 0.01
- rvis_percentile_EVS
- 54.95
Haploinsufficiency Scores
- pHI
- 0.224
- hipred
- N
- hipred_score
- 0.217
- ghis
- 0.544
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.382
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Ndufaf4
- Phenotype
Gene ontology
- Biological process
- mitochondrial respiratory chain complex I assembly
- Cellular component
- mitochondrion;mitochondrial inner membrane;mitochondrial membrane
- Molecular function
- protein binding;calmodulin binding