NUDT16L1

Chr 16

nudix hydrolase 16 like 1

Also known as: SDOS, TIRR

NCBI Gene: 84309 ENSG00000168101 UniProt: Q9BRJ7 OMIM: 617338

This protein regulates TP53BP1, a key DNA damage response factor, by controlling its recruitment to chromatin during double-strand break repair and also binds U8 snoRNA. The gene is not highly constrained against loss-of-function variants (pLI 0.0001, LOEUF 1.7), and no established human disease associations have been reported in the literature to date.

OMIM ResearchSummary from RefSeq, UniProt

Enables snoRNA binding activity. Involved in negative regulation of double-strand break repair via nonhomologous end joining. Located in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.73

Clinical Summary— NUDT16L1

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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

34 VUS of 53 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?

1.73LOEUF

pLI 0.000

Z-score 0.14

OE 0.94 (0.51–1.73)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.76Z-score

OE missense 0.80 (0.68–0.95)

93 obs / 116.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.94 (0.51–1.73)

0≤0.351.4

Missense OE?0.80 (0.68–0.95)

0≤0.61.4

Synonymous OE?1.99

0≤1.21.6

LoF obs/exp: 6 / 6.4Missense obs/exp: 93 / 116.2Syn Z: -5.91

This gene — mechanism propensity

0.6648th %ile

GOF

0.4678th %ile

LOF

0.3067th %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

53 submitted variants in ClinVar

ClinVar

Classification Summary

VUS34

Likely Benign7

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	0	34	34
Likely Benign	1	6	7
Benign	0	0	0
Total	1	40	41

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

View in ClinVar →

28 pathogenic / likely-pathogenic (of 40) ClinVar copy-number / structural variants overlap NUDT16L1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →