NFU1
Basic information
Region (hg38): 2:69396113-69437628
Previous symbols: [ "HIRIP5" ]
Links
Phenotypes
GenCC
Source:
- multiple mitochondrial dysfunctions syndrome 1 (Definitive), mode of inheritance: AR
- multiple mitochondrial dysfunctions syndrome 1 (Strong), mode of inheritance: AR
- multiple mitochondrial dysfunctions syndrome 1 (Supportive), mode of inheritance: AR
- multiple mitochondrial dysfunctions syndrome 1 (Strong), mode of inheritance: AR
- mitochondrial disease (Definitive), mode of inheritance: AR
Clinical Genomic Database
Source:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Multiple mitochondrial dysfunctions syndrome 1; Spastic paraplegia 93, autosomal recessive | 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; Musculoskeletal; Neurologic | 11156534; 21944046; 25758857; 32747156; 36256512 |
ClinVar
This is a list of variants' phenotypes submitted to
- Multiple_mitochondrial_dysfunctions_syndrome_1 (99 variants)
- not_provided (49 variants)
- Inborn_genetic_diseases (26 variants)
- not_specified (10 variants)
- Spastic_paraplegia_93,_autosomal_recessive (10 variants)
- NFU1-related_disorder (8 variants)
- Fatal_multiple_mitochondrial_dysfunctions_syndrome (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the NFU1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001002755.4. 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 | 18 | 22 | ||||
missense | 54 | 67 | ||||
nonsense | 1 | |||||
start loss | 0 | |||||
frameshift | 2 | |||||
splice donor/acceptor (+/-2bp) | 3 | |||||
Total | 8 | 8 | 58 | 19 | 2 |
Highest pathogenic variant AF is 0.0000780687
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
NFU1 | protein_coding | protein_coding | ENST00000410022 | 8 | 41879 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
0.00000415 | 0.626 | 125704 | 0 | 43 | 125747 | 0.000171 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | 0.370 | 123 | 135 | 0.910 | 0.00000623 | 1653 |
Missense in Polyphen | 40 | 45.843 | 0.87254 | 604 | ||
Synonymous | 0.598 | 42 | 47.2 | 0.889 | 0.00000222 | 473 |
Loss of Function | 0.940 | 10 | 13.8 | 0.727 | 5.80e-7 | 172 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.000938 | 0.000912 |
Ashkenazi Jewish | 0.000100 | 0.0000992 |
East Asian | 0.0000544 | 0.0000544 |
Finnish | 0.00 | 0.00 |
European (Non-Finnish) | 0.000133 | 0.000123 |
Middle Eastern | 0.0000544 | 0.0000544 |
South Asian | 0.000261 | 0.000261 |
Other | 0.000163 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Iron-sulfur cluster scaffold protein which can assemble [4Fe-4S] clusters and deliver them to target proteins. {ECO:0000269|PubMed:12886008, ECO:0000269|PubMed:27818104, ECO:0000269|PubMed:28906594}.;
- Disease
- DISEASE: Multiple mitochondrial dysfunctions syndrome 1 (MMDS1) [MIM:605711]: A severe disorder of systemic energy metabolism, resulting in weakness, respiratory failure, lack of neurologic development, lactic acidosis, hyperglycinemia and early death. Some patients show failure to thrive, pulmonary hypertension, hypotonia and irritability. Biochemical features include severe combined deficiency of the 2-oxoacid dehydrogenases, defective lipoic acid synthesis and reduction in activity of mitochondrial respiratory chain complexes. {ECO:0000269|PubMed:21944046, ECO:0000269|PubMed:22077971, ECO:0000269|PubMed:25918518, ECO:0000269|PubMed:28161430, ECO:0000269|PubMed:28906594}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.144
Intolerance Scores
- loftool
- 0.621
- rvis_EVS
- 0.42
- rvis_percentile_EVS
- 76.81
Haploinsufficiency Scores
- pHI
- 0.569
- hipred
- Y
- hipred_score
- 0.562
- ghis
- 0.455
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- H
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.900
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Nfu1
- Phenotype
Gene ontology
- Biological process
- iron-sulfur cluster assembly;protein maturation by iron-sulfur cluster transfer
- Cellular component
- nucleus;nucleoplasm;mitochondrion;cytosol
- Molecular function
- iron ion binding;protein binding;4 iron, 4 sulfur cluster binding