NFU1

NFU1 iron-sulfur cluster scaffold, the group of Mitochondrial iron-sulfur assembly components

Basic information

Region (hg38): 2:69396113-69437628

Previous symbols: [ "HIRIP5" ]

Links

ENSG00000169599NCBI:27247OMIM:608100HGNC:16287Uniprot:Q9UMS0AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • 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: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Multiple mitochondrial dysfunctions syndrome 1; Spastic paraplegia 93, autosomal recessiveARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingBiochemical; Cardiovascular; Musculoskeletal; Neurologic11156534; 21944046; 25758857; 32747156; 36256512

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NFU1 gene.

  • 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.

EffectPLPVUSLBBSum
synonymous
3
clinvar
18
clinvar
1
clinvar
22
missense
6
clinvar
5
clinvar
54
clinvar
1
clinvar
1
clinvar
67
nonsense
1
clinvar
1
start loss
0
frameshift
2
clinvar
2
splice donor/acceptor (+/-2bp)
2
clinvar
1
clinvar
3
Total 8 8 58 19 2

Highest pathogenic variant AF is 0.0000780687

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
NFU1protein_codingprotein_codingENST00000410022 841879
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.000004150.6261257040431257470.000171
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.3701231350.9100.000006231653
Missense in Polyphen4045.8430.87254604
Synonymous0.5984247.20.8890.00000222473
Loss of Function0.9401013.80.7275.80e-7172

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0009380.000912
Ashkenazi Jewish0.0001000.0000992
East Asian0.00005440.0000544
Finnish0.000.00
European (Non-Finnish)0.0001330.000123
Middle Eastern0.00005440.0000544
South Asian0.0002610.000261
Other0.0001630.000163

dbNSFP

Source: dbNSFP

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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