NT5C1A

Chr 1

5'-nucleotidase, cytosolic IA

Also known as: CN-I, CN-IA, CN1, CN1A, CNI

NCBI Gene: 84618 ENSG00000116981 UniProt: Q9BXI3 OMIM: 610525

The NT5C1A protein catalyzes the hydrolysis of ribonucleotide and deoxyribonucleotide monophosphates, with AMP as the major substrate, releasing inorganic phosphate and the corresponding nucleoside. Mutations cause autosomal recessive spastic paraplegia with intellectual disability and seizures. The gene shows low constraint against loss-of-function variants, consistent with the recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, UniProt

Cytosolic nucleotidases, such as NT5C1A, dephosphorylate nucleoside monophosphates (Hunsucker et al., 2001 [PubMed 11133996]).[supplied by OMIM, Mar 2008]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.96

Clinical Summary— NT5C1A

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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

43 VUS of 51 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?

0.96LOEUF

pLI 0.000

Z-score 1.68

OE 0.55 (0.33–0.96)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.87Z-score

OE missense 0.84 (0.75–0.95)

209 obs / 247.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.55 (0.33–0.96)

0≤0.351.4

Missense OE?0.84 (0.75–0.95)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 9 / 16.3Missense obs/exp: 209 / 247.3Syn Z: -0.09

This gene — mechanism propensity

0.6258th %ile

GOF

0.5660th %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

51 submitted variants in ClinVar

ClinVar

Classification Summary

VUS43

Likely Benign1

Benign3

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	43	0	43
Likely Benign	1	0	1
Benign	1	2	3
Total	45	2	47

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

View in ClinVar →

8 pathogenic / likely-pathogenic (of 15) ClinVar copy-number / structural variants overlap NT5C1A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →