RNPS1

Chr 16

RNA binding protein with serine rich domain 1

Also known as: E5.1

NCBI Gene: 10921ENSG00000205937UniProt: Q15287

This gene encodes a protein that is part of a post-splicing multiprotein complex involved in both mRNA nuclear export and mRNA surveillance. mRNA surveillance detects exported mRNAs with truncated open reading frames and initiates nonsense-mediated mRNA decay (NMD). When translation ends upstream from the last exon-exon junction, this triggers NMD to degrade mRNAs containing premature stop codons. This protein binds to the mRNA and remains bound after nuclear export, acting as a nucleocytoplasmic shuttling protein. This protein contains many serine residues. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]

90
ClinVar variants
28
Pathogenic / LP
0.98
pLI score· haploinsufficient
0
Active trials
Clinical Summary— RNPS1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
28 Pathogenic / Likely Pathogenic· 59 VUS of 90 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.25LOEUF
pLI 0.980
Z-score 3.20
OE 0.00 (0.00–0.25)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.19Z-score
OE missense 0.76 (0.67–0.87)
153 obs / 200.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.25)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.76 (0.67–0.87)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.10
0≤1.21.6
LoF obs/exp: 0 / 11.9Missense obs/exp: 153 / 200.6Syn Z: -0.66

ClinVar Variant Classifications

90 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic26
Likely Pathogenic2
VUS59
Likely Benign2
Benign1
26
Pathogenic
2
Likely Pathogenic
59
VUS
2
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
26
0
26
Likely Pathogenic
0
0
2
0
2
VUS
0
42
17
0
59
Likely Benign
0
0
0
2
2
Benign
0
0
0
1
1
Total04245390

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

View in ClinVar →

Protein Context — Lollipop Plot

RNPS1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
ADARp110 promotes hepatocellular carcinoma progression via stabilization of CD24 mRNA.
Sun L et al.·Proc Natl Acad Sci U S A
2025
RNPS1 functions as an oncogenic splicing factor in cervical cancer cells.
Deka B et al.·IUBMB Life
2023
Splicing activator RNPS1 suppresses errors in pre-mRNA splicing: A key factor for mRNA quality control.
Fukumura K et al.·Biochem Biophys Res Commun
2018
RNPS1 Promotes the Progression of Nonsmall Cell Lung Cancer via ETV4-Mediated Ferroptosis.
Wang L et al.·DNA Cell Biol
2026
An evolutionarily conserved role for SRm160 in 3'-end processing that functions independently of exon junction complex formation.
McCracken S et al.·J Biol Chem
2003
Exon Junction Complex Shapes the Transcriptome by Repressing Recursive Splicing.
Blazquez L et al.·Mol Cell
2018
Proteins associated with the exon junction complex also control the alternative splicing of apoptotic regulators.
Michelle L et al.·Mol Cell Biol
2012
Uncovering chikungunya virus-encoded miRNAs and host-specific targeted genes associated with antiviral immune responses: an integrated bioinformatics approach.
Ashraf S et al.·Sci Rep
2024
Whole Genome Analysis and Prognostic Model Construction Based on Alternative Splicing Events in Endometrial Cancer.
Wang C et al.·Biomed Res Int
2019Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools