SNRNP200
protein-codingsmall nuclear ribonucleoprotein U5 subunit 200, the group of Spliceosomal Bact complex|Spliceosomal P complex|Spliceosomal C complex|U5 small nuclear ribonucleoprotein|RNA helicases
Gene summary
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]
- ASCC3L1
- RP33
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~46.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0019200
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0012477
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0012477
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0012477
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0012477
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0012477
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0800098
Submitter: ClinGen
SNRNP200 gene was first reported in relation to SNRNP200-related dominant retinopathy, in a patient described with retinitis pigmentosa (adRP) in 2009 (PMID:19878916). Retinitis pigmentosa is characterized by nyctalopia (HP:0000662), reduced visual acuity (HP:0007663), rod-cone dystrophy (HP:0000510), attenuation of retinal blood vessels (HP:0007843), pigmentary retinopathy (HP:0000580), macular degeneration (HP:0000608), optic disc pallor (HP:0000543), abnormal (diminished) electroretinogram (HP:0000512), and bone spicule pigmentation of the retina (HP:0007737). To capture the overlapping spectrum of clinical presentations, this gene is curated under the disease entity "inherited retinal dystrophy". Though total score to reach a definitive classification was achieved by the addition of 27 variants (PMID: 23029027, 26720483, 21618346, 33553197, 33090715, 33598457, 19710410, 33576794, 30543658, 31486839, 26355662, 24516651, 24319334, 25356976, 32037395, 27208204) in this curation, however there is more evidence available in the literature. There are 17 SNRNP200 pathogenic and likely pathogenic variants listed on ClinVar (03/02/2022). SNRNP200 RNA was found to be highly expressed in cornea, iris, lens, vitreous body, sclera, retina, and optic nerve of the human cadaver eyes (PMID 33553197) while whole mount in situ hybridization in zebra fish revealed a generalized expression of SNRNP200 at two-cell stage, 50%-epiboly, 8-somite stage, 1pdf, and 2pdf. Furthermore, retinal cryosections showed high expression at the ciliary marginal zone at 3dpf and 5dpf (PMID 33553197). Overexpression of mutant SNRNP200 in knockout zebrafish caused generalized body and retinal defects through dominant negative effect, although in humans with SNRNP200 mutations, no systemic defects have been observed so far (PMID 33553197). In summary, SNRNP200 is definitively associated with SNRNP200-related dominant retinopathy. This has been repeatedly demonstrated in both research and clinical diagnostic settings and has been upheld over time.
Clinical Genomic Database (CGD)
Manifestation: Ophthalmologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SNRNP200 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014014.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 27 | 418 | 8 | 453 | ||
| missense | 5 | 25 | 582 | 90 | 4 | 706 |
| nonsense | 1 | 6 | 7 | |||
| start loss | 1 | 1 | ||||
| frameshift | 3 | 6 | 9 | |||
| splice donor/acceptor (+/-2bp) | 13 | 13 | ||||
| Total | 5 | 29 | 635 | 508 | 12 | 1189 |
Highest pathogenic variant AF is 0.00008303054
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_054733.2 | 45 | MANE Select | |
| Ensembl | ENSP00000317123.5 | 45 | MANE Select | |
| Ensembl | ENSP00000498933.1 | 30 | Standard | |
| Ensembl | ENSP00000550102.1 | 44 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| snrnp200 | Danio rerio | Structure: retinal rod cell Quality: physical object quality abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Spliceosome - Homo sapiens (human)
- Metabolism of RNA
- mRNA Splicing - Major Pathway
- mRNA Splicing - Minor Pathway
- mRNA Splicing
Biological Process
- cis assembly of pre-catalytic spliceosome
- spliceosome conformational change to release U4 (or U4atac) and U1 (or U11)
- mRNA splicing, via spliceosome
- osteoblast differentiation
Molecular Function
- RNA binding
- ATP-dependent RNA helicase activity
- protein binding
- ATP binding
- ATP-dependent helicase activity
Cellular Component
- nucleus
- nucleoplasm
- spliceosomal complex
- U5 snRNP
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000323853
- Coding exons
- 45
- Length
- 31224
- Individuals with no LoFs
- 125741
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 7
- Defined
- 125748
- p
- 0.0000278
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 5.94 | 610 | 1.19e+3 | 0.515 | 0.0000774 | 14073 |
| Missense (PolyPhen) | 168 | 472.67 | 0.35543 | 5603 | ||
| Synonymous | 0.769 | 436 | 457 | 0.954 | 0.0000282 | 4148 |
| Loss of Function | 9.44 | 4 | 112 | 0.0358 | 0.00000703 | 1269 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000026 | 0.000026 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: RNA helicase that plays an essential role in pre-mRNA splicing as component of the U5 snRNP and U4/U6-U5 tri-snRNP complexes. Involved in spliceosome assembly, activation and disassembly. Mediates changes in the dynamic network of RNA-RNA interactions in the spliceosome. Catalyzes the ATP-dependent unwinding of U4/U6 RNA duplices, an essential step in the assembly of a catalytically active spliceosome. {ECO:0000269|PubMed:16723661, ECO:0000269|PubMed:23045696, ECO:0000269|PubMed:8670905, ECO:0000269|PubMed:9539711}.;
- Disease
- DISEASE: Retinitis pigmentosa 33 (RP33) [MIM:610359]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. {ECO:0000269|PubMed:16723661, ECO:0000269|PubMed:19710410, ECO:0000269|PubMed:19878916, ECO:0000269|PubMed:21618346, ECO:0000269|PubMed:23029027, ECO:0000269|PubMed:23045696, ECO:0000269|PubMed:23887765, ECO:0000269|PubMed:24319334}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.168
Intolerance Scores
- LoFtool
- 0.112
- RVIS EVS
- -2.34
- RVIS percentile EVS
- 1.17
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.913
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |