NUBPL

Chr 14AR

NUBP iron-sulfur cluster assembly factor, mitochondrial

Also known as: C14orf127, IND1, MC1DN21, huInd1

NCBI Gene: 80224ENSG00000151413UniProt: Q8TB37

This gene encodes a member of the Mrp/NBP35 ATP-binding proteins family. The encoded protein is required for the assembly of the respiratory chain NADH dehydrogenase (complex I), an oligomeric enzymatic complex located in the inner mitochondrial membrane. Mutations in this gene cause mitochondrial complex I deficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

Primary Disease Associations & Inheritance

Mitochondrial complex I deficiency, nuclear type 21MIM #618242
AR
337
ClinVar variants
47
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— NUBPL
🧬
Gene-Disease Validity (ClinGen)
Leigh syndrome · ARModerate

Moderate evidence — consider for supplementary testing

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
47 Pathogenic / Likely Pathogenic· 158 VUS of 337 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.93LOEUF
pLI 0.000
Z-score 1.80
OE 0.56 (0.35–0.93)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.29Z-score
OE missense 0.94 (0.82–1.07)
160 obs / 170.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.56 (0.35–0.93)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.94 (0.82–1.07)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.83
0≤1.21.6
LoF obs/exp: 11 / 19.6Missense obs/exp: 160 / 170.5Syn Z: 1.07

ClinVar Variant Classifications

337 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic36
Likely Pathogenic11
VUS158
Likely Benign56
Benign52
Conflicting24
36
Pathogenic
11
Likely Pathogenic
158
VUS
56
Likely Benign
52
Benign
24
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
3
30
0
36
Likely Pathogenic
7
2
2
0
11
VUS
1
83
68
6
158
Likely Benign
0
2
30
24
56
Benign
0
0
52
0
52
Conflicting
—24
Total119018230337

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

View in ClinVar →

Protein Context — Lollipop Plot

NUBPL · protein map & ClinVar variants

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

Gene2Phenotype Curations

NUBPL-related mitochondrial complex I deficiency

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Mitochondrial complex I deficiency, nuclear type 21

MIM #618242

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
NUBPL mitochondrial disease: new patients and review of the genetic and clinical spectrum.
Kimonis V et al.·J Med Genet
2021Review
Expanding the Spectrum of NUBPL-Related Leukodystrophy.
Tonduti D et al.·Neuropediatrics
2023Review
Pathogenic mutations in NUBPL affect complex I activity and cold tolerance in the yeast model Yarrowia lipolytica.
Maclean AE et al.·Hum Mol Genet
2018Functional
Disulfidptosis-related gene signatures as prognostic biomarkers and predictors of immunotherapy response in HNSCC.
Qin H et al.·Front Immunol
2025
Imaging Patterns Characterizing Mitochondrial Leukodystrophies.
Roosendaal SD et al.·AJNR Am J Neuroradiol
2021
Next-generation sequencing in molecular diagnosis: NUBPL mutations highlight the challenges of variant detection and interpretation.
Tucker EJ et al.·Hum Mutat
2012
Pathogenic variants in NUBPL result in failure to assemble the matrix arm of complex I and cause a complex leukoencephalopathy with thalamic involvement.
Friederich MW et al.·Mol Genet Metab
2020Case report
Identifying disulfidptosis-related biomarkers in epilepsy based on integrated bioinformatics and experimental analyses.
Li S et al.·Neurobiol Dis
2025
Identification of disulfidptosis-related genes and subgroups in spinal cord injury.
Tao Y et al.·Spinal Cord
2025
Novel compound heterozygous pathogenic variants in nucleotide-binding protein like protein (NUBPL) cause leukoencephalopathy with multi-systemic involvement.
Protasoni M et al.·Mol Genet Metab
2020Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools