NPM2

Chr 8

nucleophosmin/nucleoplasmin 2

The NPM2 protein functions as a core histone chaperone involved in chromatin reprogramming during fertilization and early embryonic development, including sperm DNA decondensation. Mutations in NPM2 cause infertility due to oocyte maturation defect with autosomal recessive inheritance. This gene shows low constraint against loss-of-function variants, which is consistent with its specialized role in reproductive development.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
2
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.95
LOEUF
DN
Mechanism· predicted
Clinical SummaryNPM2
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
0.95LOEUF
pLI 0.001
Z-score 1.70
OE 0.51 (0.290.95)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.22Z-score
OE missense 1.06 (0.911.23)
123 obs / 116.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.51 (0.290.95)
00.351.4
Missense OE1.06 (0.911.23)
00.61.4
Synonymous OE0.98
01.21.6
LoF obs/exp: 7 / 13.8Missense obs/exp: 123 / 116.2Syn Z: 0.10
DN
0.6453th %ile
GOF
0.2497th %ile
LOF
0.2872th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

NPM2 · protein map & ClinVar variants

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

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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Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗