PRPF8

pre-mRNA processing factor 8, the group of Spliceosomal C complex|U5 small nuclear ribonucleoprotein|JAMM/MPN+ metallopeptidase family|Spliceosomal Bact complex|Spliceosomal P complex

Basic information

Region (hg38): 17:1650629-1684867

Previous symbols: [ "RP13" ]

Links

ENSG00000174231

∙ NCBI:10594 ∙ OMIM:607300 ∙ HGNC:17340 ∙ Uniprot:Q6P2Q9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

retinitis pigmentosa (Supportive), mode of inheritance: AD
neurodevelopmental disorder (Strong), mode of inheritance: AD
retinitis pigmentosa 13 (Definitive), mode of inheritance: AD
retinitis pigmentosa 13 (Strong), mode of inheritance: AD
inherited retinal dystrophy (Definitive), mode of inheritance: AD
neurodevelopmental disorder (Moderate), mode of inheritance: AD
glaucoma (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Retinitis pigmentosa 13	AD	General	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	Ophthalmologic	11468273; 20232351; 22039234

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PRPF8 gene.

not_provided (1379 variants)
Retinal_dystrophy (101 variants)
Retinitis_pigmentosa (90 variants)
Inborn_genetic_diseases (85 variants)
Retinitis_pigmentosa_13 (66 variants)
not_specified (14 variants)
PRPF8-related_disorder (13 variants)
Retinitis_Pigmentosa,_Dominant (3 variants)
Neurodevelopmental_disorder (2 variants)
Neurodevelopmental_abnormality (2 variants)
Developmental_disorder (2 variants)
Retinitis_pigmentosa_14 (1 variants)
Irido-corneo-trabecular_dysgenesis (1 variants)
Choroideremia (1 variants)
Autosomal_dominant_retinitis_pigmentosa (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PRPF8 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000006445.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			22 clinvar	518 clinvar	19 clinvar	559
missense	11 clinvar	37 clinvar	482 clinvar	7 clinvar		537
nonsense	6 clinvar	6 clinvar	5 clinvar			17
start loss						0
frameshift	13 clinvar	8 clinvar	6 clinvar			27
splice donor/acceptor (+/-2bp)	1 clinvar	3 clinvar	3 clinvar			7
Total	31	54	518	525	19

Highest pathogenic variant AF is 0.00007131924

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PRPF8	protein_coding	protein_coding	ENST00000572621	42	34254

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	2.13e-10	125719	0	29	125748	0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	8.28	458	1.30e+3	0.353	0.0000874	15433
Missense in Polyphen		106	537.48	0.19722		6315
Synonymous	-4.38	624	500	1.25	0.0000312	4463
Loss of Function	9.10	14	123	0.114	0.00000736	1397

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000304	0.000304
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000109	0.000109
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000132	0.000123
Middle Eastern	0.000109	0.000109
South Asian	0.0000653	0.0000653
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

Function: FUNCTION: Functions as a scaffold that mediates the ordered assembly of spliceosomal proteins and snRNAs. Required for the assembly of the U4/U6-U5 tri-snRNP complex. Functions as scaffold that positions spliceosomal U2, U5 and U6 snRNAs at splice sites on pre-mRNA substrates, so that splicing can occur. Interacts with both the 5' and the 3' splice site. {ECO:0000269|PubMed:20595234, ECO:0000303|PubMed:15840809}.;
Disease: DISEASE: Retinitis pigmentosa 13 (RP13) [MIM:600059]: 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:11468273, ECO:0000269|PubMed:11910553, ECO:0000269|PubMed:12714658, ECO:0000269|PubMed:17317632, ECO:0000269|Ref.36}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Spliceosome - Homo sapiens (human);mRNA Processing;Metabolism of RNA;mRNA Splicing - Major Pathway;mRNA Splicing - Minor Pathway;mRNA Splicing;Processing of Capped Intron-Containing Pre-mRNA (Consensus)

Recessive Scores

pRec: 0.210

Intolerance Scores

loftool: 0.184
rvis_EVS: -3.03
rvis_percentile_EVS: 0.5

Haploinsufficiency Scores

pHI: 0.824
hipred: Y
hipred_score: 0.765
ghis: 0.666

Essentials

essential_gene_CRISPR: E
essential_gene_CRISPR2: E
essential_gene_gene_trap: E
gene_indispensability_pred: E
gene_indispensability_score: 0.986

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Prpf8
Phenotype: vision/eye phenotype; pigmentation phenotype;

Zebrafish Information Network

Gene name: prpf8
Affected structure: myeloid leukocyte
Phenotype tag: abnormal
Phenotype quality: decreased amount

Gene ontology

Biological process: spliceosomal tri-snRNP complex assembly;RNA splicing, via transesterification reactions;mRNA splicing, via spliceosome;mRNA processing;RNA splicing;cellular response to lipopolysaccharide;cellular response to tumor necrosis factor
Cellular component: nucleus;nucleoplasm;U5 snRNP;membrane;nuclear speck;U4/U6 x U5 tri-snRNP complex;U2-type precatalytic spliceosome;U2-type catalytic step 2 spliceosome;catalytic step 2 spliceosome
Molecular function: second spliceosomal transesterification activity;RNA binding;protein binding;U6 snRNA binding;U1 snRNA binding;U2 snRNA binding;U5 snRNA binding;K63-linked polyubiquitin modification-dependent protein binding;pre-mRNA intronic binding