NME2

Chr 17

NME/NM23 nucleoside diphosphate kinase 2

Also known as: NDK2, NDKB, NDPK B, NDPK-B, NDPKB, NM23-H2, NM23B, PUF

NCBI Gene: 4831UniProt: P22392

Nucleoside diphosphate kinase (NDK) exists as a hexamer composed of 'A' (encoded by NME1) and 'B' (encoded by this gene) isoforms. Multiple alternatively spliced transcript variants have been found for this gene. Read-through transcription from the neighboring upstream gene (NME1) generates naturally-occurring transcripts (NME1-NME2) that encode a fusion protein comprised of sequence sharing identity with each individual gene product. [provided by RefSeq, Nov 2010]

14
ClinVar variants
11
Pathogenic / LP
0.00
pLI score
0.9
Missense Z
1.46
LOEUF
0
Active trials
Clinical Summary— NME2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
11 Pathogenic / Likely Pathogenic· 2 VUS of 14 total submissions
Some data sources returned errors (1)

ensembl: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.46LOEUF
pLI 0.000
Z-score 0.27
OE 0.92 (0.60–1.46)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.88Z-score
OE missense 0.81 (0.70–0.93)
132 obs / 163.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.92 (0.60–1.46)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.81 (0.70–0.93)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.89
0≤1.21.6
LoF obs/exp: 13 / 14.1Missense obs/exp: 132 / 163.5Syn Z: 0.67

ClinVar Variant Classifications

14 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic1
VUS2
Likely Benign1
10
Pathogenic
1
Likely Pathogenic
2
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
10
0
10
Likely Pathogenic
0
0
1
0
1
VUS
0
2
0
0
2
Likely Benign
1
0
0
0
1
Benign
0
0
0
0
0
Total1211014

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

View in ClinVar →

Protein Context — Lollipop Plot

NME2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Nuclear functions of NME proteins.
Puts GS et al.·Lab Invest
2018Review
NME2 modulates HCC progression through 4EBP1 phosphorylation and autophagy regulation independent of mTOR.
Chen W et al.·Hepatol Commun
2025
WWOX tuning of oleic acid signaling orchestrates immunosuppressive macrophage polarization and sensitizes hepatocellular carcinoma to immunotherapy.
Liu S et al.·J Immunother Cancer
2024
Learning about the functions of NME/NM23: lessons from knockout mice to silencing strategies.
Boissan M et al.·Naunyn Schmiedebergs Arch Pharmacol
2011Review
The HGF/SF Mouse Model of UV-Induced Melanoma as an In Vivo Sensor for Metastasis-Regulating Gene.
Leonard MK et al.·Int J Mol Sci
2017Review
Differentially expressed and survival-related proteins of lung adenocarcinoma with bone metastasis.
Yang M et al.·Cancer Med
2018
Effect of NME2 and SAMHD1 genetic polymorphisms involved in Ara-C metabolism on the response to induction chemotherapy in adult acute myeloid leukemia.
Fouad LA et al.·J Egypt Natl Canc Inst
2025
Machine learning-derived cellular senescence index for predicting prognosis and drug sensitivity in patients with renal cell carcinoma.
Meng L et al.·Front Immunol
2025Cohort
Characterization of Vemurafenib-Resistant Melanoma Cell Lines Reveals Novel Hallmarks of Targeted Therapy Resistance.
Radić M et al.·Int J Mol Sci
2022
Comprehensive molecular profiling of UV-induced metastatic melanoma in Nme1/Nme2-deficient mice reveals novel markers of survival in human patients.
Leonard MK et al.·Oncogene
2021Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Multicomponent Oxidative Nitrile Thiazolidination Reaction for Selective Modification of N-terminal Dimethylation Posttranslational Modification
Emenike B et al.·J Am Chem Soc
2023
Extracellular Vesicle-Mediated Metastasis Suppressors NME1 and NME2 Modify Lipid Metabolism in Fibroblasts
Mátyási B et al.·Cancers (Basel)
2022
Exploring the structural, photophysical and optoelectronic properties of a diaryl heptanoid curcumin derivative and identification as a SARS-CoV-2 inhibitor
Archana VP et al.·J Mol Struct
2023
Synthesis of Cyclopropyl Carbocyclic Nucleosides via P(NMe2)3-Mediated Reductive Cyclopropanation.
Huang KX et al.·J Org Chem
2025
Synthesis and characterization of pyrrole-based group 4 PNP pincer complexes
Tomsu G et al.·Monatsh Chem
2024
A Precise Synthetic Toolbox: H-Bond-Assisted Quadruple Reactivity of o-Dimethylaminoaryloximes
Tsybulin SV et al.·J Org Chem
2025
Rational Design of Enhanced Nme2Cas9 and Nme2 Smu Cas9 Nucleases and Base Editors
Bamidele N et al.·bioRxiv
2024
Molecular Ferroelectric [(NMe2)3PCH2Cl]PbI3 Showing Two-Step Switching Second-Order Nonlinear Optics.
Wang Q et al.·Inorg Chem
2025
Thiosemicarbazone Derivatives Developed to Overcome COTI-2 Resistance
Pósa V et al.·Cancers (Basel)
2022
Top 9 full-text resultsSearch PubTator3 ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

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