PRPF4

pre-mRNA processing factor 4, the group of WD repeat domain containing|U4/U6 small nuclear ribonucleoprotein

Basic information

Region (hg38): 9:113275642-113294009

Links

ENSG00000136875 ∙ NCBI:9128 ∙ OMIM:607795 ∙ HGNC:17349 ∙ Uniprot:O43172 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• retinitis pigmentosa 70 (Strong), mode of inheritance: AD
• retinitis pigmentosa (Supportive), mode of inheritance: AD
• retinitis pigmentosa 70 (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Retinitis pigmentosa 70	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	24419317

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PRPF4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PRPF4 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			1	66	5	72
missense		1	119	2	1	123
nonsense						0
start loss						0
frameshift						0
inframe indel			2			2
splice donor/acceptor (+/-2bp)			1			1
splice region			15	20	1	36
non coding			11	47	7	65
Total	0	1	134	115	13

Variants in PRPF4

This is a list of pathogenic ClinVar variants found in the PRPF4 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-113275646-C-T			Uncertain significance (Dec 20, 2022)
9-113275652-A-G		PRPF4-related disorder	Likely benign (Jan 19, 2024)
9-113275654-T-C			Uncertain significance (Oct 17, 2022)
9-113275656-A-T			Uncertain significance (Jul 22, 2022)
9-113275657-C-T			Uncertain significance (Jul 03, 2022)
9-113275661-C-G			Uncertain significance (Oct 19, 2022)
9-113275672-C-T		PRPF4-related disorder	Likely benign (Apr 02, 2019)
9-113275747-G-A			Uncertain significance (Mar 03, 2020)
9-113275748-C-T		Retinal dystrophy	Uncertain significance (Jan 01, 2022)
9-113275751-C-T		not specified	Uncertain significance (Jul 23, 2024)
9-113275760-C-T			Uncertain significance (Mar 16, 2022)
9-113275761-C-G			Benign (Sep 20, 2023)
9-113275768-A-G			Uncertain significance (Nov 10, 2021)
9-113275778-G-T			Likely benign (Oct 11, 2020)
9-113275782-G-A			Likely benign (Oct 17, 2022)
9-113275787-C-T			Likely benign (Oct 19, 2023)
9-113276526-A-T			Likely benign (Jul 06, 2022)
9-113276527-T-A			Uncertain significance (Oct 13, 2022)
9-113276529-C-T			Likely benign (Jun 27, 2022)
9-113276537-T-G			Uncertain significance (Apr 10, 2022)
9-113276539-A-G			Uncertain significance (Nov 20, 2021)
9-113276544-G-C			Uncertain significance (Oct 14, 2022)
9-113276551-A-T			Uncertain significance (Jul 27, 2021)
9-113276569-G-A			Uncertain significance (Mar 10, 2022)
9-113276571-C-T			Likely benign (Jan 14, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PRPF4	protein_coding	protein_coding	ENST00000374198	14	17563

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000705	125742	0	3	125745	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.99	210	309	0.681	0.0000176	3405
Missense in Polyphen		45	91.508	0.49176		1040
Synonymous	0.333	108	112	0.960	0.00000638	1004
Loss of Function	4.94	3	34.2	0.0878	0.00000203	356

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)	0.0000176	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex). {ECO:0000269|PubMed:25383878, ECO:0000269|PubMed:28781166}.
• Disease: DISEASE: Retinitis pigmentosa 70 (RP70) [MIM:615922]: 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:24419317, ECO:0000269|PubMed:25383878}. 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;Processing of Capped Intron-Containing Pre-mRNA (Consensus)

Recessive Scores

• pRec: 0.127

Intolerance Scores

• loftool: 0.0736
• rvis_EVS: -0.38
• rvis_percentile_EVS: 27.69

Haploinsufficiency Scores

• pHI: 0.331
• hipred: Y
• hipred_score: 0.783
• ghis: 0.684

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.840

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Prpf4

Zebrafish Information Network

• Gene name: prpf4
• Affected structure: photoreceptor cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: RNA splicing, via transesterification reactions;mRNA splicing, via spliceosome;RNA processing;RNA splicing
• Cellular component: nucleus;nucleoplasm;spliceosomal complex;Cajal body;nuclear speck;U4/U6 x U5 tri-snRNP complex;U4/U6 snRNP;U2-type precatalytic spliceosome;spliceosomal snRNP complex
• Molecular function: protein binding;U6 snRNA binding;U4 snRNA binding