PRPF18

protein-coding

pre-mRNA processing factor 18, the group of Spliceosomal C complex

Gene summary

Pre-mRNA splicing occurs in 2 sequential transesterification steps. The protein encoded by this gene is found to be essential for the catalytic step II in pre-mRNA splicing process. It is found in the spliceosome, and contains seven WD repeats, which function in protein-protein interactions. This protein has a sequence similarity to the yeast splicing factor Prp18. [provided by RefSeq, Jul 2008]

MANE transcript

NM_003675.4

Inheritance

—

ClinVar variants

U:29

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.47

Max pathogenic AF

—

Genomic locus

chr10:13,586,939-13,668,445

External References & Databases

Ensembl (ENSG00000165630)

Transcript & Mutation Effects

hg38 • Region Span ~81.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PRPF18 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 24

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003675.4. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			27 clinvar			27
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	29	0	0	29

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 95 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003675.4	RefSeq	NP_003666.1	10	MANE Select
ENST00000378572.8	Ensembl	ENSP00000367835.3	10	MANE Select
NM_001395875.1	RefSeq	NP_001382804.1	11	Standard
NM_001395876.1	RefSeq	NP_001382805.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Spliceosome - Homo sapiens (human)
mRNA Processing

Biological Process

generation of catalytic spliceosome for second transesterification step
mRNA processing
RNA splicing
nuclear retention of unspliced pre-mRNA at the site of transcription

Molecular Function

second spliceosomal transesterification activity

Cellular Component

nucleus
spliceosomal complex
U5 snRNP
nuclear speck
U4/U6 x U5 tri-snRNP complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000378572
Coding exons: 10
Length: 43942
Individuals with no LoFs: 125729
Homozygous LoFs: 0
Heterozygous LoFs: 17
Defined: 125746
p: 0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.54	87	184	0.472	0.00000980	2247
Missense (PolyPhen)		15	64.782	0.23155		783
Synonymous	-0.272	71	68.1	1.04	0.00000376	603
Loss of Function	2.17	9	19.3	0.467	8.12e-7	265

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000063	0.000062	rare
South Asian	0.000033	0.000033	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Participates in the second step of pre-mRNA splicing. {ECO:0000269|PubMed:9000057}.;

Recessive Scores

pRec: 0.113

Intolerance Scores

LoFtool: 0.330
RVIS EVS: 0.08
RVIS percentile EVS: 60.09

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.847

Gene Damage Prediction

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