NFU1

Chr 2AR

NFU1 iron-sulfur cluster scaffold

Also known as: CGI-33, HIRIP, HIRIP5, MMDFS, MMDS1, NIFUC, Nfu, NifU

NCBI Gene: 27247 ENSG00000169599 UniProt: Q9UMS0 OMIM: 608100

The NFU1 protein localizes to mitochondria where it assembles and transfers 4Fe-4S clusters to target apoproteins including succinate dehydrogenase and lipoic acid synthase. Mutations cause multiple mitochondrial dysfunctions syndrome-1 and spastic paraplegia 93 through autosomal recessive inheritance. The pathogenic mechanism involves dominant-negative effects.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a protein that is localized to mitochondria and plays a critical role in iron-sulfur cluster biogenesis. The encoded protein assembles and transfers 4Fe-4S clusters to target apoproteins including succinate dehydrogenase and lipoic acid synthase. Mutations in this gene are a cause of multiple mitochondrial dysfunctions syndrome-1, and pseudogenes of this gene are located on the short arms of chromosomes 1 and 3. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Multiple mitochondrial dysfunctions syndrome 1MIM #605711

Spastic paraplegia 93, autosomal recessiveMIM #620938

Clinical highlights

Gene-disease validity (ClinGen)

mitochondrial disease · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

1.23

LOEUF

LOF

Mechanism· G2P