NME3

Chr 16

NME/NM23 nucleoside diphosphate kinase 3

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

NCBI Gene: 4832 ENSG00000103024 UniProt: Q13232 OMIM: 601817

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.

OMIM ResearchSummary from RefSeq, UniProt

Enables nucleoside diphosphate kinase activity. Involved in DNA repair; mitochondrial fusion; and nucleoside triphosphate biosynthetic process. Located in mitochondrial outer membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.95

Clinical Summary— NME3

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Population Constraint (gnomAD)

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

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ClinVar Variants

37 VUS of 52 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?

1.95LOEUF

pLI 0.000

Z-score -1.45

OE 1.68 (0.93–1.95)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.69Z-score

OE missense 1.21 (1.03–1.42)

106 obs / 87.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.68 (0.93–1.95)

0≤0.351.4

Missense OE?1.21 (1.03–1.42)

0≤0.61.4

Synonymous OE?1.36

0≤1.21.6

LoF obs/exp: 9 / 5.4Missense obs/exp: 106 / 87.9Syn Z: -1.76

This gene — mechanism propensity

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

52 submitted variants in ClinVar

ClinVar

Classification Summary

VUS37

Likely Benign3

Benign1

Conflicting1

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	0	37	0	0	37
Likely Benign	1	0	1	1	3
Benign	0	1	0	0	1
Conflicting	—				1
Total	1	38	1	1	42

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

View in ClinVar →

40 pathogenic / likely-pathogenic (of 56) ClinVar copy-number / structural variants overlap NME3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →