GeneBe

PRPF19

protein-coding

pre-mRNA processing factor 19, the group of NineTeen complex|Spliceosomal C complex|U-box domain containing|WD repeat domain containing

Gene summary

Enables identical protein binding activity and ubiquitin-ubiquitin ligase activity. Involved in several processes, including DNA damage checkpoint signaling; mRNA splicing, via spliceosome; and protein K63-linked ubiquitination. Acts upstream of or within protein polyubiquitination. Located in cytoplasm; nuclear lumen; and site of double-strand break. Part of Prp19 complex and U2-type catalytic step 2 spliceosome. Implicated in syndromic intellectual disability. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:
  • PRP19

MANE transcript

NM_014502.5

Inheritance

AD

ClinVar variants

P:1U:60

Top phenotype

neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr11:60,890,547-60,906,585

External References & Databases

Ensembl (ENSG00000110107)NCBI Gene (27339)OMIM (608330)HGNC:17896GenCCUniProt (Q9UMS4)AlphaFoldClinVar (PRPF19)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~16.0 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

PRPF19-related neurodevelopmental disorderMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:1040005

Submitter: G2P

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PRPF19 variants in ClinVar

4 Conditions Cataloged
Inborn genetic diseasesTotal: 43
not providedTotal: 1
AutismTotal: 1
Non-immune hydrops fetalisTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014502.5. 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.

EffectPLPVUSLBBSum
synonymous
3
clinvar
 3
missense
1
clinvar
51
clinvar
 52
nonsense
1
clinvar
 1
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
5
clinvar
 5
Total01600061
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 12 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_014502.5RefSeqNP_055317.116MANE Select
ENST00000227524.9EnsemblENSP00000227524.416MANE Select
ENST00000535326.1EnsemblENSP00000445435.14Standard
ENST00000540473.5EnsemblENSP00000443031.14Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Ubiquitin mediated proteolysis - Homo sapiens (human)
  • Spliceosome - Homo sapiens (human)
  • DNA Repair
  • Metabolism of RNA
  • mRNA Splicing - Major Pathway

Biological Process

  • protein polyubiquitination
  • spliceosomal tri-snRNP complex assembly
  • spliceosomal complex assembly
  • generation of catalytic spliceosome for first transesterification step
  • mRNA splicing, via spliceosome

Molecular Function

  • ubiquitin-protein transferase activity
  • protein binding
  • ubiquitin-ubiquitin ligase activity
  • identical protein binding
  • ubiquitin protein ligase activity

Cellular Component

  • Prp19 complex
  • nucleus
  • nucleoplasm
  • DNA replication factor A complex
  • cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000227524
Coding exons
16
Length
15859
Individuals with no LoFs
0
Homozygous LoFs
0
Heterozygous LoFs
0
Defined
0
p
0.00
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense3.741203040.3950.00001783276
Missense (PolyPhen)1490.340.15497916
Synonymous1.131081240.8710.000008011009
Loss of Function4.91028.10.000.00000128319

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)00.0absent
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Ubiquitin-protein ligase which is a core component of several complexes mainly involved pre-mRNA splicing and DNA repair. Core component of the PRP19C/Prp19 complex/NTC/Nineteen complex which is part of the spliceosome and participates in its assembly, its remodeling and is required for its activity. During assembly of the spliceosome, mediates 'Lys-63'-linked polyubiquitination of the U4 spliceosomal protein PRPF3. Ubiquitination of PRPF3 allows its recognition by the U5 component PRPF8 and stabilizes the U4/U5/U6 tri-snRNP spliceosomal complex (PubMed:20595234). Recruited to RNA polymerase II C-terminal domain (CTD) and the pre-mRNA, it may also couple the transcriptional and spliceosomal machineries (PubMed:21536736). The XAB2 complex, which contains PRPF19, is also involved in pre- mRNA splicing, transcription and transcription-coupled repair (PubMed:17981804). Beside its role in pre-mRNA splicing PRPF19, as part of the PRP19-CDC5L complex, plays a role in the DNA damage response/DDR. It is recruited to the sites of DNA damage by the RPA complex where PRPF19 directly ubiquitinates RPA1 and RPA2. 'Lys-63'-linked polyubiquitination of the RPA complex allows the recruitment of the ATR-ATRIP complex and the activation of ATR, a master regulator of the DNA damage response (PubMed:24332808). May also play a role in DNA double-strand break (DSB) repair by recruiting the repair factor SETMAR to altered DNA (PubMed:18263876). As part of the PSO4 complex may also be involved in the DNA interstrand cross-links/ICLs repair process (PubMed:16223718). In addition, may also mediate 'Lys-48'-linked polyubiquitination of substrates and play a role in proteasomal degradation (PubMed:11435423). May play a role in the biogenesis of lipid droplets (By similarity). May play a role in neural differentiation possibly through its function as part of the spliceosome (By similarity). {ECO:0000250|UniProtKB:Q99KP6, ECO:0000250|UniProtKB:Q9JMJ4, ECO:0000269|PubMed:11082287, ECO:0000269|PubMed:11435423, ECO:0000269|PubMed:12960389, ECO:0000269|PubMed:15660529, ECO:0000269|PubMed:16223718, ECO:0000269|PubMed:16332694, ECO:0000269|PubMed:16388800, ECO:0000269|PubMed:17349974, ECO:0000269|PubMed:18263876, ECO:0000269|PubMed:21536736, ECO:0000269|PubMed:24332808, ECO:0000303|PubMed:17981804, ECO:0000303|PubMed:20595234}.;

Recessive Scores

pRec
0.180

Intolerance Scores

RVIS EVS
-0.56
RVIS percentile EVS
19.31

Essentials

Essential (CRISPR)
E
Essential (CRISPR2)
E
Essential (gene trap)
E
Indispensability pred.
E
Indispensability score
0.818

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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