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

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 (12 variants)
• Retinitis pigmentosa 13 (3 variants)
• Retinal dystrophy (3 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.

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			18	435	30	483
missense	7	23	356	2		388
nonsense	1	4	6			11
start loss						0
frameshift	2	4	12			18
inframe indel	1		3			4
splice donor/acceptor (+/-2bp)		2	4			6
splice region			51	59	7	117
non coding			25	191	24	240
Total	11	33	424	628	54

Variants in PRPF8

This is a list of pathogenic ClinVar variants found in the PRPF8 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-1650635-T-C		Retinitis pigmentosa	Uncertain significance (Mar 30, 2018)
17-1650677-C-T		Retinitis pigmentosa	Likely benign (Jan 12, 2018)
17-1650730-G-C		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
17-1650730-G-T		Retinitis pigmentosa	Uncertain significance (Jan 12, 2018)
17-1650766-G-A		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
17-1650766-G-C		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
17-1650774-GAGGCTGAAGCAGGAGGCAGGGAAACGGTCAGGC-G			Uncertain significance (Jul 03, 2022)
17-1650791-C-A		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
17-1650800-G-A		Retinitis pigmentosa	Likely benign (Jan 13, 2018)
17-1650803-C-G			Pathogenic (Aug 03, 2023)
17-1650805-G-A			Likely benign (Mar 23, 2022)
17-1650808-A-C		Retinal dystrophy	Uncertain significance (Oct 01, 2023)
17-1650810-A-T		Retinal dystrophy	Pathogenic (Oct 17, 2022)
17-1650811-C-T			Likely benign (Jan 03, 2020)
17-1650813-G-C			Uncertain significance (Jun 27, 2024)
17-1650814-G-T		Retinal dystrophy	Uncertain significance (Aug 12, 2018)
17-1650815-TCCTCCCGATCCGCAGAGTAAA-T			Pathogenic (Nov 01, 2022)
17-1650815-T-TC		Retinitis pigmentosa 13	Likely pathogenic (May 28, 2019)
17-1650816-C-A			Uncertain significance (May 27, 2022)
17-1650816-C-G		Retinal dystrophy	Likely pathogenic (Jan 01, 2022)
17-1650818-TC-T			Pathogenic/Likely pathogenic (Sep 23, 2024)
17-1650819-C-A			Likely pathogenic (Jan 21, 2021)
17-1650819-C-T		Retinitis pigmentosa 13 • Retinal dystrophy	Conflicting classifications of pathogenicity (Oct 01, 2023)
17-1650819-C-CCCGAT			Uncertain significance (Jun 13, 2023)
17-1650821-C-G			Uncertain significance (Jul 19, 2022)

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