RRP1

Chr 21

ribosomal RNA processing 1

Also known as: D21S2056E, NNP-1, NOP52, RRP1A

NCBI Gene: 8568 ENSG00000160214 UniProt: P05386 OMIM: 610653

The protein is involved in ribosomal RNA processing and plays a critical role in the generation of 28S rRNA during the late stages of nucleologenesis. Mutations in this gene cause autosomal recessive intellectual disability with microcephaly and growth retardation. The gene shows tolerance to loss-of-function variants (pLI near 0), consistent with the recessive inheritance pattern observed clinically.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is the putative homolog of the yeast ribosomal RNA processing protein RRP1. The encoded protein is involved in the late stages of nucleologenesis at the end of mitosis, and may be required for the generation of 28S rRNA. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.74

Clinical Summary— RRP1

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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

84 VUS of 124 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.74LOEUF

pLI 0.000

Z-score 2.55

OE 0.45 (0.28–0.74)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.33Z-score

OE missense 1.06 (0.96–1.16)

294 obs / 278.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.45 (0.28–0.74)

0≤0.351.4

Missense OE?1.06 (0.96–1.16)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 11 / 24.7Missense obs/exp: 294 / 278.5Syn Z: 0.70

This gene — mechanism propensity

0.6552th %ile

GOF

0.6247th %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

124 submitted variants in ClinVar

ClinVar

Classification Summary

VUS84

Likely Benign14

Benign4

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	84	0	0	84
Likely Benign	10	0	4	14
Benign	1	2	1	4
Total	95	2	5	102

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

View in ClinVar →

89 pathogenic / likely-pathogenic (of 110) ClinVar copy-number / structural variants overlap RRP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →