SNRNP200

Chr 2AD

small nuclear ribonucleoprotein U5 subunit 200

Also known as: ASCC3L1, BRR2, HELIC2, RP33, U5-200KD

NCBI Gene: 23020ENSG00000144028UniProt: O75643OMIM: 601664

SNRNP200 encodes an RNA helicase that catalyzes ATP-dependent unwinding of U4/U6 RNA duplexes, an essential step in spliceosome assembly and pre-mRNA splicing. Mutations cause autosomal dominant retinitis pigmentosa 33, a progressive retinal degeneration leading to vision loss. This gene is extremely intolerant to loss-of-function variants (pLI >0.99), indicating that heterozygous inactivating variants are likely pathogenic.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismADLOEUF 0.081 OMIM phenotype
Clinical Summary— SNRNP200
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Gene-Disease Validity (ClinGen)
SNRNP200-related dominant retinopathy · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
11 unique Pathogenic / Likely Pathogenic· 218 VUS of 500 total submissions
Explore recent and relevant literature in Research Assistant →
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GeneReview available — SNRNP200
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.08LOEUF
pLI 1.000
Z-score 9.44
OE 0.04 (0.02–0.08)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
5.94Z-score
OE missense 0.51 (0.48–0.55)
610 obs / 1185.1 exp
Constrained

Extremely missense-constrained (top ~0.01%)

Observed / Expected Ratios
LoF OE0.04 (0.02–0.08)
0≤0.351.4
Missense OE0.51 (0.48–0.55)
0≤0.61.4
Synonymous OE0.95
0≤1.21.6
LoF obs/exp: 4 / 111.7Missense obs/exp: 610 / 1185.1Syn Z: 0.77
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongSNRNP200-related retinal dystrophyOTHERAR
definitiveSNRNP200-related retinitis pigmentosaOTHERAD
DN
0.2997th %ile
GOF
0.3094th %ile
LOF
0.73top 10%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFprediction above median · 18% of P/LP variants are LoF · LOEUF 0.08
DN1 literature citation

Literature Evidence

DNIn conclusion, this study reports a novel heterozygous SNRNP200c.C6088T mutation, which is evidenced to cause RP via a dominant-negative effect.PMID:33553197

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

500 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic5
VUS218
Likely Benign230
Benign7
Conflicting2
6
Pathogenic
5
Likely Pathogenic
218
VUS
230
Likely Benign
7
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
2
1
2
0
5
VUS
2
190
20
6
218
Likely Benign
0
15
109
106
230
Benign
0
3
1
3
7
Conflicting
—2
Total4209138115468

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

View in ClinVar →

Protein Context — Lollipop Plot

SNRNP200 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
SNRNP200 Mutations Cause Autosomal Dominant Retinitis Pigmentosa
Zhang T et al.·Front Med (Lausanne)
2021
miR-6807-5p Inhibited the Odontogenic Differentiation of Human Dental Pulp Stem Cells Through Directly Targeting METTL7A
Wang N et al.·Front Cell Dev Biol
2021
U5 snRNP Core Proteins Are Key Components of the Defense Response against Viral Infection through Their Roles in Programmed Cell Death and Interferon Induction
Boudreault S et al.·Viruses
2022
Systematic evaluation of AML-associated antigens identifies anti-U5 SNRNP200 therapeutic antibodies for the treatment of acute myeloid leukemia
Knorr K et al.·Nat Cancer
2023
Generation of two induced pluripotent stem cell lines from a patient with recessive inherited retinal disease caused by compound heterozygous mutations in SNRNP200.
Zhang D et al.·Stem Cell Res
2021
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients