NUBPL

Chr 14

NUBP iron-sulfur cluster assembly factor, mitochondrial

Also known as: C14orf127, IND1, MC1DN21, huInd1

NCBI Gene: 80224 ENSG00000151413 UniProt: Q8TB37

The protein functions as an iron-sulfur cluster transfer protein required for assembly of mitochondrial respiratory chain complex I (NADH dehydrogenase). Mutations cause mitochondrial complex I deficiency with autosomal recessive inheritance, typically presenting with multi-system involvement including neurological, cardiac, and metabolic manifestations. The gene shows minimal constraint against loss-of-function variants (pLI 0.00001), consistent with its recessive inheritance pattern.

ResearchSummary from RefSeq, OMIM, UniProt

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]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.93

Clinical Summary— NUBPL

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Gene-Disease Validity (ClinGen)

Leigh syndrome · ARModerate

Moderate evidence — consider for supplementary testing

2 total gene-disease associations curated

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

22 unique Pathogenic / Likely Pathogenic· 142 VUS of 306 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?

0.93LOEUF

pLI 0.000

Z-score 1.80

OE 0.56 (0.35–0.93)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.29Z-score

OE missense 0.94 (0.82–1.07)

160 obs / 170.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.56 (0.35–0.93)

0≤0.351.4

Missense OE?0.94 (0.82–1.07)

0≤0.61.4

Synonymous OE?0.83

0≤1.21.6

LoF obs/exp: 11 / 19.6Missense obs/exp: 160 / 170.5Syn Z: 1.07

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveNUBPL-related mitochondrial complex I deficiencyLOFAR

This gene — mechanism propensity

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

0.7327th %ile

GOF

0.5563th %ile

LOF

0.3356th %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

306 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11

Likely Pathogenic11

VUS142

Likely Benign56

Benign52

Conflicting24

Pathogenic

Likely Pathogenic

142

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	7	3	1	0	11
Likely Pathogenic	9	2	0	0	11
VUS	2	85	49	6	142
Likely Benign	0	2	30	24	56
Benign	0	0	52	0	52
Conflicting	—				24
Total	18	92	132	30	296

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

View in ClinVar →

26 pathogenic / likely-pathogenic (of 44) ClinVar copy-number / structural variants overlap NUBPL — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →