NUF2

Chr 1

NUF2 component of NDC80 kinetochore complex

Also known as: CDCA1, CT106, NUF2R

NCBI Gene: 83540ENSG00000143228UniProt: Q9BZD4OMIM: 611772

This gene encodes a protein that is highly similar to yeast Nuf2, a component of a conserved protein complex associated with the centromere. Yeast Nuf2 disappears from the centromere during meiotic prophase when centromeres lose their connection to the spindle pole body, and plays a regulatory role in chromosome segregation. The encoded protein is found to be associated with centromeres of mitotic HeLa cells, which suggests that this protein is a functional homolog of yeast Nuf2. Alternatively spliced transcript variants that encode the same protein have been described. [provided by RefSeq, Jul 2008]

OMIMResearchGenerating clinical summary…
DNmechanismLOEUF 0.71
Clinical Summary— NUF2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
1 unique Pathogenic / Likely Pathogenic· 56 VUS of 84 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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?
0.71LOEUF
pLI 0.000
Z-score 2.71
OE 0.44 (0.28–0.71)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
1.37Z-score
OE missense 0.75 (0.66–0.85)
173 obs / 231.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.44 (0.28–0.71)
0≤0.351.4
Missense OE?0.75 (0.66–0.85)
0≤0.61.4
Synonymous OE?0.88
0≤1.21.6
LoF obs/exp: 12 / 27.3Missense obs/exp: 173 / 231.7Syn Z: 0.86

This gene — mechanism propensity

DN
0.6746th %ile
GOF
0.5955th %ile
LOF
0.2483th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

84 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1
VUS56
Likely Benign2
1
Pathogenic
56
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
0
0
1
Likely Pathogenic
0
0
0
0
0
VUS
0
56
0
0
56
Likely Benign
0
2
0
0
2
Benign
0
0
0
0
0
Total0590059

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

View in ClinVar →

16 pathogenic / likely-pathogenic (of 17) ClinVar copy-number / structural variants overlap NUF2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

NUF2 · protein map & ClinVar variants

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

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