NME3

Chr 16

NME/NM23 nucleoside diphosphate kinase 3

Also known as: DR-nm23, NDK3, NDPK-C, NDPKC, NM23-H3, NM23H3, c371H6.2

The NME3 protein functions as a nucleoside diphosphate kinase that maintains nucleoside triphosphate homeostasis and plays critical roles in mitochondrial membrane fusion and DNA repair. Mutations cause autosomal recessive nephronophthisis, a ciliopathy presenting with progressive kidney disease that can lead to end-stage renal failure in childhood or adolescence. The gene shows minimal constraint against loss-of-function variants (very low pLI), consistent with recessive inheritance where heterozygous carriers are typically unaffected.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.95
Clinical SummaryNME3
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
1.95LOEUF
pLI 0.000
Z-score -1.45
OE 1.68 (0.931.95)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.69Z-score
OE missense 1.21 (1.031.42)
106 obs / 87.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.68 (0.931.95)
00.351.4
Missense OE1.21 (1.031.42)
00.61.4
Synonymous OE1.36
01.21.6
LoF obs/exp: 9 / 5.4Missense obs/exp: 106 / 87.9Syn Z: -1.76
DN
0.6356th %ile
GOF
0.5660th %ile
LOF
0.3842th %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

NME3 · 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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