NIT2

Chr 3

nitrilase family member 2

Also known as: HEL-S-8a

NCBI Gene: 56954 ENSG00000114021 UniProt: Q9NQR4

Enables omega-amidase activity. Involved in asparagine metabolic process; glutamine metabolic process; and oxaloacetate metabolic process. Located in centrosome and cytosol. [provided by Alliance of Genome Resources, Jul 2025]

Research

ResearchGenerating clinical summary…

DNmechanismLOEUF 1.77

Clinical Summary— NIT2

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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

32 VUS of 51 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.77LOEUF

pLI 0.000

Z-score -1.09

OE 1.28 (0.92–1.77)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.40Z-score

OE missense 0.91 (0.80–1.04)

146 obs / 160.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.28 (0.92–1.77)

0≤0.351.4

Missense OE?0.91 (0.80–1.04)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 23 / 18.0Missense obs/exp: 146 / 160.3Syn Z: -0.59

This gene — mechanism propensity

0.6744th %ile

GOF

0.5955th %ile

LOF

0.4038th %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

VUS32

Likely Benign1

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	32	32
Likely Benign	1	1
Benign	0	0
Total	33	33

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

View in ClinVar →

9 pathogenic / likely-pathogenic (of 13) ClinVar copy-number / structural variants overlap NIT2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →