SNRNP200

Chr 2AD

small nuclear ribonucleoprotein U5 subunit 200

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

Pre-mRNA splicing is catalyzed by the spliceosome, a complex of specialized RNA and protein subunits that removes introns from a transcribed pre-mRNA segment. The spliceosome consists of small nuclear RNA proteins (snRNPs) U1, U2, U4, U5 and U6, together with approximately 80 conserved proteins. U5 snRNP contains nine specific proteins. This gene encodes one of the U5 snRNP-specific proteins. This protein belongs to the DEXH-box family of putative RNA helicases. It is a core component of U4/U6-U5 snRNPs and appears to catalyze an ATP-dependent unwinding of U4/U6 RNA duplices. Mutations in this gene cause autosomal-dominant retinitis pigmentosa. Alternatively spliced transcript variants encoding different isoforms have been found, but the full-length nature of these variants has not been determined. [provided by RefSeq, Mar 2010]

Primary Disease Associations & Inheritance

Retinitis pigmentosa 33MIM #610359
AD
0
Active trials
8
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.08
LOEUF· LoF intol.
Multiple*
Mechanism· predicted
Clinical SummarySNRNP200
🧬
Gene-Disease Validity (ClinGen)
SNRNP200-related dominant retinopathy · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.08LOEUF
pLI 1.000
Z-score 9.44
OE 0.04 (0.020.08)
Highly constrained

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

Missense Constraint
5.94Z-score
OE missense 0.51 (0.480.55)
610 obs / 1185.1 exp
Constrained

Extremely missense-constrained (top ~0.01%)

Observed / Expected Ratios
LoF OE0.04 (0.020.08)
00.351.4
Missense OE0.51 (0.480.55)
00.61.4
Synonymous OE0.95
01.21.6
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 · 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

0 submitted variants 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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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