NT5M

Chr 17

5',3'-nucleotidase, mitochondrial

Also known as: dNT-2, dNT2, mdN

NCBI Gene: 56953 ENSG00000205309 UniProt: Q9NPB1 OMIM: 605292

The protein is a mitochondrial matrix 5' nucleotidase that dephosphorylates uracil and thymine deoxyribonucleotides to protect mitochondrial DNA replication from excess dTTP. Mutations cause autosomal recessive spastic paraplegia-45, which presents with progressive spasticity and weakness of the lower extremities. The gene shows low constraint against loss-of-function variants, consistent with recessive inheritance where heterozygous carriers are typically unaffected.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a 5' nucleotidase that localizes to the mitochondrial matrix. This enzyme dephosphorylates the 5'- and 2'(3')-phosphates of uracil and thymine deoxyribonucleotides. The gene is located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOEUF 1.85

Clinical Summary— NT5M

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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

44 VUS of 53 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.85LOEUF

pLI 0.000

Z-score -0.69

OE 1.25 (0.78–1.85)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.18Z-score

OE missense 0.95 (0.82–1.11)

115 obs / 120.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.25 (0.78–1.85)

0≤0.351.4

Missense OE?0.95 (0.82–1.11)

0≤0.61.4

Synonymous OE?1.12

0≤1.21.6

LoF obs/exp: 11 / 8.8Missense obs/exp: 115 / 120.5Syn Z: -0.67

ClinVar Variant Classifications

53 submitted variants in ClinVar

ClinVar

Classification Summary

VUS44

Likely Benign2

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	44	44
Likely Benign	2	2
Benign	0	0
Total	46	46

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

View in ClinVar →

116 pathogenic / likely-pathogenic (of 124) ClinVar copy-number / structural variants overlap NT5M — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →