PRPF6

pre-mRNA processing factor 6, the group of U5 small nuclear ribonucleoprotein

Basic information

Region (hg38): 20:63981131-64033100

Previous symbols: [ "C20orf14" ]

Links

ENSG00000101161 ∙ NCBI:24148 ∙ OMIM:613979 ∙ HGNC:15860 ∙ Uniprot:O94906 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• retinitis pigmentosa 60 (Limited), mode of inheritance: AD
• retinitis pigmentosa (Supportive), mode of inheritance: AD
• retinitis pigmentosa 60 (Limited), mode of inheritance: AD
• retinitis pigmentosa 60 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Retinitis pigmentosa 60	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	21549338

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PRPF6 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PRPF6 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			6	158	14	178
missense			189	2		191
nonsense		1	4			5
start loss						0
frameshift			6			6
inframe indel			2	1		3
splice donor/acceptor (+/-2bp)			7		1	8
splice region			20	29	5	54
non coding			16	94	30	140
Total	0	1	230	255	45

Variants in PRPF6

This is a list of pathogenic ClinVar variants found in the PRPF6 region.

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

Position	Type	Phenotype	Significance	ClinVar
20-63981139-A-G		Retinitis pigmentosa	Uncertain significance (Jan 12, 2018)
20-63981147-C-G		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
20-63981157-C-T		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
20-63981160-C-T		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
20-63981163-A-G		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
20-63981164-C-T		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
20-63981167-C-T		Retinitis pigmentosa	Benign (Jan 13, 2018)
20-63981168-G-A		Retinitis pigmentosa	Likely benign (Jan 12, 2018)
20-63981171-G-A		Retinitis pigmentosa	Benign (Jan 13, 2018)
20-63981192-C-T		Retinitis pigmentosa	Uncertain significance (Jan 12, 2018)
20-63981193-C-T		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
20-63981221-C-T		Retinitis pigmentosa	Benign (Jan 13, 2018)
20-63981266-G-C			Likely benign (Jul 29, 2022)
20-63981269-C-T			Likely benign (Nov 13, 2023)
20-63981279-C-T			Uncertain significance (Oct 17, 2022)
20-63981287-C-T		Retinitis pigmentosa • Retinal dystrophy	Benign (Jan 19, 2024)
20-63981293-C-T			Likely benign (Oct 14, 2020)
20-63981296-C-T			Likely benign (Mar 10, 2022)
20-63981302-G-A		Retinitis pigmentosa	Conflicting classifications of pathogenicity (Jul 01, 2024)
20-63981305-G-C			Likely benign (Jul 06, 2022)
20-63981306-C-T		Retinitis pigmentosa	Conflicting classifications of pathogenicity (Aug 30, 2023)
20-63981311-C-T			Likely benign (Jun 16, 2023)
20-63981322-G-A		Retinitis pigmentosa	Benign (Jan 31, 2024)
20-63981322-GC-AA			Uncertain significance (Nov 27, 2023)
20-63981323-C-T			Uncertain significance (Nov 15, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PRPF6	protein_coding	protein_coding	ENST00000266079	21	51966

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00321	0.997	125712	0	36	125748	0.000143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.85	242	567	0.427	0.0000391	6160
Missense in Polyphen		28	145.19	0.19285		1559
Synonymous	-0.750	241	227	1.06	0.0000161	1833
Loss of Function	4.78	15	52.3	0.287	0.00000283	575

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000270	0.000268
Ashkenazi Jewish	0.000198	0.000198
East Asian	0.000219	0.000217
Finnish	0.000191	0.000185
European (Non-Finnish)	0.000123	0.000114
Middle Eastern	0.000219	0.000217
South Asian	0.000163	0.000163
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in pre-mRNA splicing as component of the U4/U6- U5 tri-snRNP complex, one of the building blocks of the spliceosome (PubMed:28781166, PubMed:21549338). Enhances dihydrotestosterone-induced transactivation activity of AR, as well as dexamethasone-induced transactivation activity of NR3C1, but does not affect estrogen-induced transactivation. {ECO:0000269|PubMed:12039962, ECO:0000269|PubMed:21549338, ECO:0000269|PubMed:28781166}.
• 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: 0.357

Intolerance Scores

• loftool: 0.461
• rvis_EVS: -1.38
• rvis_percentile_EVS: 4.39

Haploinsufficiency Scores

• pHI: 0.0951
• hipred: Y
• hipred_score: 0.706
• ghis: 0.639

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.982

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Prpf6
• Phenotype: hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype

Gene ontology

• Biological process: spliceosomal tri-snRNP complex assembly;spliceosomal complex assembly;RNA splicing, via transesterification reactions;mRNA splicing, via spliceosome;RNA localization;RNA splicing;positive regulation of transcription by RNA polymerase II
• Cellular component: nucleus;nucleoplasm;spliceosomal complex;U5 snRNP;membrane;nuclear speck;U4/U6 x U5 tri-snRNP complex;U2-type precatalytic spliceosome;catalytic step 2 spliceosome
• Molecular function: transcription coactivator activity;RNA binding;protein binding;ribonucleoprotein complex binding;androgen receptor binding