NOL12

Chr 22

nucleolar protein 12

Also known as: Nop25, VITO, dJ37E16.7

NCBI Gene: 79159 ENSG00000273899 UniProt: Q9UGY1 OMIM: 621385

NOL12 encodes a multifunctional RNA binding protein that regulates nucleolar organization and size, participates in DNA stress response and genome integrity maintenance, and controls levels of key ribosomal proteins fibrillarin and nucleolin. Mutations cause autosomal recessive developmental delay with seizures and microcephaly. The gene shows tolerance to loss-of-function variants (pLI 0.001, LOEUF 1.13), consistent with the recessive inheritance pattern observed clinically.

OMIM ResearchSummary from RefSeq, UniProt

Enables identical protein binding activity. Predicted to be located in cytoplasm and nucleus. Predicted to be active in nucleolus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.13

Clinical Summary— NOL12

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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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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.13LOEUF

pLI 0.001

Z-score 1.28

OE 0.57 (0.31–1.13)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.26Z-score

OE missense 0.94 (0.81–1.08)

129 obs / 137.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.57 (0.31–1.13)

0≤0.351.4

Missense OE?0.94 (0.81–1.08)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 6 / 10.5Missense obs/exp: 129 / 137.6Syn Z: -0.44

This gene — mechanism propensity

0.76top 25%

GOF

0.5759th %ile

LOF

0.2968th %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.