NOP16

Chr 5

NOP16 nucleolar protein

Also known as: HSPC111, HSPC185

NCBI Gene: 51491 ENSG00000048162 UniProt: Q9Y3C1 OMIM: 612861

This gene encodes a nucleolus-localized protein involved in ribosome biogenesis. Mutations cause autosomal recessive neurodevelopmental disorder with seizures, hypotonia, and feeding difficulties, typically presenting in infancy. The gene is not highly constrained against loss-of-function variants, consistent with recessive inheritance.

OMIM ResearchSummary from RefSeq

This gene encodes a protein that is localized to the nucleolus. Expression of this gene is induced by estrogens and Myc protein and is a marker of poor patient survival in breast cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.18

Clinical Summary— NOP16

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Population Constraint (gnomAD)

Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

26 VUS of 36 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?

1.18LOEUF

pLI 0.012

Z-score 1.25

OE 0.52 (0.25–1.18)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.49Z-score

OE missense 0.88 (0.76–1.02)

120 obs / 136.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.52 (0.25–1.18)

0≤0.351.4

Missense OE?0.88 (0.76–1.02)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 4 / 7.8Missense obs/exp: 120 / 136.2Syn Z: 0.38

This gene — mechanism propensity

0.7034th %ile

GOF

0.3788th %ile

LOF

0.2582th %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

36 submitted variants in ClinVar

ClinVar

Classification Summary

VUS26

Likely Benign1

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	1	25	26
Likely Benign	0	1	1
Benign	0	0	0
Total	1	26	27

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

View in ClinVar →

47 pathogenic / likely-pathogenic (of 55) ClinVar copy-number / structural variants overlap NOP16 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →