RRP1B

Chr 21

ribosomal RNA processing 1B

Also known as: KIAA0179, NNP1L, Nnp1, PPP1R136, RRP1

NCBI Gene: 23076 ENSG00000160208 UniProt: Q14684 OMIM: 610654

RRP1B encodes a transcriptional coactivator that regulates DNA damage-induced apoptosis, ribosome biogenesis, and mRNA splicing. Mutations cause autosomal recessive neurodevelopmental disorder with seizures and brain abnormalities, typically presenting in early childhood. The gene is not highly constrained to loss-of-function variants.

OMIM ResearchSummary from RefSeq, UniProt

Enables transcription coactivator activity. Involved in cellular response to virus; positive regulation of apoptotic process; and positive regulation of transcription by RNA polymerase II. Located in chromosome; granular component; and nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.78

Clinical Summary— RRP1B

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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

85 VUS of 118 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?

0.78LOEUF

pLI 0.000

Z-score 2.63

OE 0.54 (0.38–0.78)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.39Z-score

OE missense 0.81 (0.74–0.89)

334 obs / 413.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.54 (0.38–0.78)

0≤0.351.4

Missense OE?0.81 (0.74–0.89)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 20 / 37.3Missense obs/exp: 334 / 413.3Syn Z: -0.39

This gene — mechanism propensity

0.6357th %ile

GOF

0.5367th %ile

LOF

0.4429th %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

118 submitted variants in ClinVar

ClinVar

Classification Summary

VUS85

Likely Benign11

Benign3

Conflicting1

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	0	85	0	0	85
Likely Benign	0	9	0	2	11
Benign	0	1	1	1	3
Conflicting	—				1
Total	0	95	1	3	100

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

View in ClinVar →

91 pathogenic / likely-pathogenic (of 116) ClinVar copy-number / structural variants overlap RRP1B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →