NUBP2

Chr 16

NUBP iron-sulfur cluster assembly factor 2, cytosolic

Also known as: CFD1, CIAO6, NBP 2

This protein is an ATP and metal-binding component of the cytosolic iron-sulfur protein assembly machinery, functioning as a heterotetramer with NUBP1 to transfer iron-sulfur clusters to target proteins and regulate cilium formation. Mutations cause autosomal recessive multiple mitochondrial dysfunctions syndrome, typically presenting in infancy with severe neurodegeneration, developmental delay, and multi-organ involvement. The gene shows tolerance to loss-of-function variants (pLI 0.0009), consistent with the recessive inheritance pattern.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.20
Clinical SummaryNUBP2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.20LOEUF
pLI 0.001
Z-score 1.14
OE 0.61 (0.331.20)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.07Z-score
OE missense 1.02 (0.901.15)
182 obs / 179.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.61 (0.331.20)
00.351.4
Missense OE1.02 (0.901.15)
00.61.4
Synonymous OE1.21
01.21.6
LoF obs/exp: 6 / 9.9Missense obs/exp: 182 / 179.3Syn Z: -1.52
DN
0.77top 25%
GOF
0.72top 25%
LOF
0.2483th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

NUBP2 · 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

No active trials found for this gene.

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Clinical Literature
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