GeneBe

PRPF31

protein-coding

pre-mRNA processing factor 31, the group of U4/U6 small nuclear ribonucleoprotein

Gene summary

This gene encodes a component of the spliceosome complex and is one of several retinitis pigmentosa-causing genes. When the gene product is added to the spliceosome complex, activation occurs.[provided by RefSeq, Jan 2009]

Previous symbols:
  • RP11

MANE transcript

NM_015629.4

Inheritance

AD

ClinVar variants

P:308U:223B:153

Top phenotype

Retinitis pigmentosa 11

gnomAD constraint

pLI —, LoF o/e 0.12

Max pathogenic AF

—

Genomic locus

chr19:54,115,410-54,131,719

External References & Databases

Ensembl (ENSG00000105618)NCBI Gene (26121)OMIM (606419)HGNC:15446GenCCUniProt (Q8WWY3)AlphaFoldClinVar (PRPF31)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~16.3 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

retinitis pigmentosaSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0019200

Submitter: Orphanet

PRPF31-related retinopathyDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0800395

Submitter: ClinGen

*PRPF31* was first reported in relation to an inherited retinal dystrophy, described as autosomal dominant retinitis pigmentosa (adRP), in 2001 (Vithana et al., PMID: 11545739). To account for a spectrum of retinal phenotypes that may be caused by variants in this gene, and in accordance with the ClinGen Lumping and Splitting guidelines, the disease entity used for this curation is PRPF31-related retinopathy. This condition is characterized by night blindness (onset in teens), progressive visual loss, and blindness (onset in 30s). Ten variants (missense, in-frame indel, nonsense, frameshift, complex rearrangement) that have been reported in 10 probands in 06 publications (PMIDs: 11545739, 12714658, 12923864, 23288994, 29375987, 20939871) are included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. Interestingly, incomplete penetrance has been frequently observed in families with *PRPF31* pathogenic variants. There are over 200 *PRPF31* pathogenic and likely pathogenic variants listed on ClinVar (07/05/2022). The mechanism of pathogenicity is reported to be LOF. This gene-disease relationship is also supported by functional studies in patient derived organoids and retinal pigment epithelium, and *Prpf31+/-* mouse (PMIDs: 30315276, 20811066). In summary, *PRPF31* is definitively associated with PRPF31-releated retinopathy. This has been repeatedly demonstrated in both the research and clinical diagnostic settings and has been upheld over time. This clinical validity classification was approved by the ClinGen Retina GCEP on July 7, 2022 (SOP v9).

retinitis pigmentosa 11STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0010828

Submitter: Labcorp Genetics (formerly Invitae)

retinitis pigmentosa 11DEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0010828

Submitter: G2P

retinitis pigmentosa 11STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0010828

Submitter: PanelApp Australia

retinitis pigmentosa 11DEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0010828

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Retinitis pigmentosa 11AD

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

Refs: 5764686; 9345108; 11545739; 12923864; 17325180; 19506198; 19618371; 20939871; 23041261Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PRPF31 variants in ClinVar

12 Conditions Cataloged
not providedTotal: 638
PRPF31-related disorderTotal: 188
not specifiedTotal: 138
Retinal dystrophyTotal: 95
Retinitis pigmentosaTotal: 94
Retinitis pigmentosa 11Total: 86
Inborn genetic diseasesTotal: 41
Retinal disorderTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015629.4. 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.

EffectPLPVUSLBBSum
synonymous
12
clinvar
134
clinvar
6
clinvar
 152
missense
4
clinvar
18
clinvar
203
clinvar
13
clinvar
 238
nonsense
38
clinvar
23
clinvar
 61
start loss
3
clinvar
2
clinvar
 5
frameshift
81
clinvar
64
clinvar
2
clinvar
 147
splice donor/acceptor (+/-2bp)
35
clinvar
40
clinvar
6
clinvar
 81
Total1611472231476684

Highest pathogenic variant AF is 0.00002479055

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 41 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_015629.4RefSeqNP_056444.313MANE Select
ENST00000321030.9EnsemblENSP00000324122.413MANE Select
ENST00000391755.1EnsemblENSP00000375635.113Standard
ENST00000391755.2EnsemblENSP00000375635.113Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
prpf31Danio rerio

Structure: photoreceptor cell

Quality: decreased amount

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
  • Processing of Capped Intron-Containing Pre-mRNA

Biological Process

  • spliceosomal tri-snRNP complex assembly
  • mRNA splicing, via spliceosome
  • snoRNA localization
  • ribonucleoprotein complex localization

Molecular Function

  • RNA binding
  • protein binding
  • U4 snRNA binding
  • U4atac snRNA binding
  • ribonucleoprotein complex binding

Cellular Component

  • nucleus
  • nucleoplasm
  • U2-type spliceosomal complex
  • U4 snRNP
  • U4atac snRNP

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000321030
Coding exons
13
Length
16304
Individuals with no LoFs
125703
Homozygous LoFs
0
Heterozygous LoFs
1
Defined
125704
p
0.00000398
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense3.051643170.5180.00002313227
Missense (PolyPhen)58133.090.435781221
Synonymous-0.4021431371.040.0000112971
Loss of Function4.14325.60.1170.00000121312

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.00000880.0000088rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11867543, PubMed:28781166). Required for the assembly of the U4/U5/U6 tri-snRNP complex, one of the building blocks of the spliceosome (PubMed:11867543). {ECO:0000269|PubMed:11867543, ECO:0000269|PubMed:28781166}.;
Disease
DISEASE: Retinitis pigmentosa 11 (RP11) [MIM:600138]: 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:11545739, ECO:0000269|PubMed:12444105, ECO:0000269|PubMed:12923864, ECO:0000269|PubMed:17412961, ECO:0000269|PubMed:8808602}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.315

Intolerance Scores

LoFtool
0.170
RVIS EVS
-1.09
RVIS percentile EVS
7.05

Essentials

Essential (CRISPR)
E
Essential (CRISPR2)
E
Essential (gene trap)
E
Indispensability pred.
E
Indispensability score
0.993

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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