SNRNP200

Chr 2AD

small nuclear ribonucleoprotein U5 subunit 200

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

NCBI Gene: 23020 ENSG00000144028 OMIM: 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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

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

17 unique Pathogenic / Likely Pathogenic· 604 VUS of 1468 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 OE?0.04 (0.02–0.08)

0≤0.351.4

Missense OE?0.51 (0.48–0.55)

0≤0.61.4

Synonymous OE?0.95

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

This gene — mechanism propensity

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.1

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

References

1.PMID 33553197 ↗

ClinVar Variant Classifications

1468 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5

Likely Pathogenic12

VUS604

Likely Benign692

Benign41

Conflicting82

Pathogenic

Likely Pathogenic

604

VUS

692

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	5	0	0	5
Likely Pathogenic	2	10	0	0	12
VUS	16	500	66	22	604
Likely Benign	0	53	286	353	692
Benign	0	5	19	17	41
Conflicting	—				82
Total	18	573	371	392	1,436

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

View in ClinVar →

32 pathogenic / likely-pathogenic (of 70) ClinVar copy-number / structural variants overlap SNRNP200 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →