NFU1

Chr 2

NFU1 iron-sulfur cluster scaffold

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

NCBI Gene: 27247ENSG00000169599UniProt: Q9UMS0

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.

ResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismLOEUF 1.23
Clinical Summary— NFU1
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Gene-Disease Validity (ClinGen)
mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
29 unique Pathogenic / Likely Pathogenic· 84 VUS of 231 total submissions
Explore recent and relevant literature in Research Assistant →
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.23LOEUF
pLI 0.000
Z-score 0.94
OE 0.73 (0.45–1.23)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.37Z-score
OE missense 0.91 (0.79–1.06)
123 obs / 135.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.73 (0.45–1.23)
0≤0.351.4
Missense OE0.91 (0.79–1.06)
0≤0.61.4
Synonymous OE0.89
0≤1.21.6
LoF obs/exp: 10 / 13.8Missense obs/exp: 123 / 135.1Syn Z: 0.60
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveNFU1-related multiple mitochondrial dysfunctions syndromeLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6744th %ile
GOF
0.5758th %ile
LOF
0.3261th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

231 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic11
VUS84
Likely Benign69
Benign33
Conflicting10
18
Pathogenic
11
Likely Pathogenic
84
VUS
69
Likely Benign
33
Benign
10
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
6
10
0
18
Likely Pathogenic
3
4
4
0
11
VUS
2
58
21
3
84
Likely Benign
0
0
47
22
69
Benign
0
3
29
1
33
Conflicting
—10
Total77111126225

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

NFU1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients