NUBP2

Chr 16

NUBP iron-sulfur cluster assembly factor 2, cytosolic

Also known as: CFD1, CIAO6, NBP 2

NCBI Gene: 10101 ENSG00000095906 UniProt: Q9Y5Y2 OMIM: 610779

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.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes an adenosine triphosphate (ATP) and metal-binding protein that is required for the assembly of cyotosolic iron-sulfur proteins. The encoded protein functions in a heterotetramer with nucleotide-binding protein 1 (NUBP1). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2013]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.20

Clinical Summary— NUBP2

⚡

Population Constraint (gnomAD)

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

📋

ClinVar Variants

64 VUS of 87 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.20LOEUF

pLI 0.001

Z-score 1.14

OE 0.61 (0.33–1.20)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.07Z-score

OE missense 1.02 (0.90–1.15)

182 obs / 179.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.61 (0.33–1.20)

0≤0.351.4

Missense OE?1.02 (0.90–1.15)

0≤0.61.4

Synonymous OE?1.21

0≤1.21.6

LoF obs/exp: 6 / 9.9Missense obs/exp: 182 / 179.3Syn Z: -1.52

This gene — mechanism propensity

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

87 submitted variants in ClinVar

ClinVar

Classification Summary

VUS64

Likely Benign6

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	1	63	0	64
Likely Benign	0	6	0	6
Benign	0	1	1	2
Total	1	70	1	72

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

View in ClinVar →

39 pathogenic / likely-pathogenic (of 57) ClinVar copy-number / structural variants overlap NUBP2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →