PRPF19
pre-mRNA processing factor 19, the group of NineTeen complex|Spliceosomal C complex|U-box domain containing|WD repeat domain containing
Basic information
Region (hg38): 11:60890547-60906585
Previous symbols: [ "PRP19" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PRPF19 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 14 | 14 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 14 | 0 | 0 |
Variants in PRPF19
This is a list of pathogenic ClinVar variants found in the PRPF19 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 11-60891186-G-A | Uncertain significance (Oct 16, 2020) | |||
| 11-60891197-A-G | Inborn genetic diseases | Uncertain significance (Mar 24, 2023) | ||
| 11-60891255-C-T | Inborn genetic diseases | Uncertain significance (Apr 08, 2024) | ||
| 11-60897882-T-A | Inborn genetic diseases | Uncertain significance (Jul 05, 2023) | ||
| 11-60898868-C-T | Inborn genetic diseases | Uncertain significance (Feb 27, 2024) | ||
| 11-60898913-T-C | Inborn genetic diseases | Uncertain significance (Jun 10, 2024) | ||
| 11-60899172-G-C | Inborn genetic diseases | Uncertain significance (Sep 25, 2023) | ||
| 11-60899214-T-C | Inborn genetic diseases | Uncertain significance (Nov 09, 2021) | ||
| 11-60899258-G-A | Inborn genetic diseases | Uncertain significance (Dec 21, 2023) | ||
| 11-60899301-G-C | Inborn genetic diseases | Uncertain significance (Apr 05, 2023) | ||
| 11-60900604-C-T | Inborn genetic diseases | Uncertain significance (Aug 19, 2024) | ||
| 11-60900616-T-C | Non-immune hydrops fetalis | Uncertain significance (Apr 29, 2021) | ||
| 11-60900865-T-C | Inborn genetic diseases | Uncertain significance (Nov 14, 2024) | ||
| 11-60901320-T-C | Inborn genetic diseases | Uncertain significance (Apr 13, 2023) | ||
| 11-60902635-T-G | Inborn genetic diseases | Uncertain significance (Jun 18, 2024) | ||
| 11-60902809-G-T | Inborn genetic diseases | Uncertain significance (Aug 14, 2023) | ||
| 11-60902830-G-C | Inborn genetic diseases | Uncertain significance (Oct 20, 2023) | ||
| 11-60903721-C-T | Inborn genetic diseases | Uncertain significance (Sep 21, 2023) | ||
| 11-60903724-T-C | Inborn genetic diseases | Uncertain significance (Jan 23, 2023) | ||
| 11-60903742-G-C | Inborn genetic diseases | Uncertain significance (May 08, 2024) | ||
| 11-60903835-A-G | Inborn genetic diseases | Uncertain significance (May 14, 2024) | ||
| 11-60903850-C-T | Inborn genetic diseases | Uncertain significance (Sep 04, 2024) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PRPF19 | protein_coding | protein_coding | ENST00000227524 | 16 | 15859 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.0000488 | 0 | 0 | 0 | 0 | 0.00 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.74 | 120 | 304 | 0.395 | 0.0000178 | 3276 |
| Missense in Polyphen | 14 | 90.34 | 0.15497 | 916 | ||
| Synonymous | 1.13 | 108 | 124 | 0.871 | 0.00000801 | 1009 |
| Loss of Function | 4.91 | 0 | 28.1 | 0.00 | 0.00000128 | 319 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Ubiquitin-protein ligase which is a core component of several complexes mainly involved pre-mRNA splicing and DNA repair. Core component of the PRP19C/Prp19 complex/NTC/Nineteen complex which is part of the spliceosome and participates in its assembly, its remodeling and is required for its activity. During assembly of the spliceosome, mediates 'Lys-63'-linked polyubiquitination of the U4 spliceosomal protein PRPF3. Ubiquitination of PRPF3 allows its recognition by the U5 component PRPF8 and stabilizes the U4/U5/U6 tri-snRNP spliceosomal complex (PubMed:20595234). Recruited to RNA polymerase II C-terminal domain (CTD) and the pre-mRNA, it may also couple the transcriptional and spliceosomal machineries (PubMed:21536736). The XAB2 complex, which contains PRPF19, is also involved in pre- mRNA splicing, transcription and transcription-coupled repair (PubMed:17981804). Beside its role in pre-mRNA splicing PRPF19, as part of the PRP19-CDC5L complex, plays a role in the DNA damage response/DDR. It is recruited to the sites of DNA damage by the RPA complex where PRPF19 directly ubiquitinates RPA1 and RPA2. 'Lys-63'-linked polyubiquitination of the RPA complex allows the recruitment of the ATR-ATRIP complex and the activation of ATR, a master regulator of the DNA damage response (PubMed:24332808). May also play a role in DNA double-strand break (DSB) repair by recruiting the repair factor SETMAR to altered DNA (PubMed:18263876). As part of the PSO4 complex may also be involved in the DNA interstrand cross-links/ICLs repair process (PubMed:16223718). In addition, may also mediate 'Lys-48'-linked polyubiquitination of substrates and play a role in proteasomal degradation (PubMed:11435423). May play a role in the biogenesis of lipid droplets (By similarity). May play a role in neural differentiation possibly through its function as part of the spliceosome (By similarity). {ECO:0000250|UniProtKB:Q99KP6, ECO:0000250|UniProtKB:Q9JMJ4, ECO:0000269|PubMed:11082287, ECO:0000269|PubMed:11435423, ECO:0000269|PubMed:12960389, ECO:0000269|PubMed:15660529, ECO:0000269|PubMed:16223718, ECO:0000269|PubMed:16332694, ECO:0000269|PubMed:16388800, ECO:0000269|PubMed:17349974, ECO:0000269|PubMed:18263876, ECO:0000269|PubMed:21536736, ECO:0000269|PubMed:24332808, ECO:0000303|PubMed:17981804, ECO:0000303|PubMed:20595234}.;
- Pathway
- Ubiquitin mediated proteolysis - Homo sapiens (human);Spliceosome - Homo sapiens (human);DNA Repair;Metabolism of RNA;mRNA Splicing - Major Pathway;Formation of TC-NER Pre-Incision Complex;mRNA Splicing;Processing of Capped Intron-Containing Pre-mRNA;Dual incision in TC-NER;Gap-filling DNA repair synthesis and ligation in TC-NER;Transcription-Coupled Nucleotide Excision Repair (TC-NER);Nucleotide Excision Repair
(Consensus)
Recessive Scores
- pRec
- 0.180
Intolerance Scores
- loftool
- rvis_EVS
- -0.56
- rvis_percentile_EVS
- 19.31
Haploinsufficiency Scores
- pHI
- 0.605
- hipred
- Y
- hipred_score
- 0.825
- ghis
- 0.632
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.818
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Prpf19
- Phenotype
- cellular phenotype; embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype;
Gene ontology
- Biological process
- protein polyubiquitination;spliceosomal tri-snRNP complex assembly;spliceosomal complex assembly;generation of catalytic spliceosome for first transesterification step;mRNA splicing, via spliceosome;inner cell mass cell proliferation;transcription-coupled nucleotide-excision repair;double-strand break repair via nonhomologous end joining;lipid biosynthetic process;proteasomal protein catabolic process;cellular protein localization;positive regulation of neuron differentiation;positive regulation of mRNA splicing, via spliceosome;positive regulation of astrocyte differentiation;protein K63-linked ubiquitination;signal transduction involved in DNA damage checkpoint
- Cellular component
- Prp19 complex;nucleus;nucleoplasm;DNA replication factor A complex;cytoplasm;lipid droplet;spindle;membrane;nuclear speck;site of double-strand break;U2-type catalytic step 1 spliceosome;U2-type catalytic step 2 spliceosome;catalytic step 2 spliceosome
- Molecular function
- ubiquitin-protein transferase activity;protein binding;ubiquitin-ubiquitin ligase activity;identical protein binding;ubiquitin protein ligase activity