PRPF19

Chr 11

pre-mRNA processing factor 19

Also known as: NMP200, PRP19, PSO4, SNEV, UBOX4, hPSO4

NCBI Gene: 27339ENSG00000110107UniProt: Q9UMS4

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. [provided by Alliance of Genome Resources, Jul 2025]

46
ClinVar variants
11
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— PRPF19
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
11 Pathogenic / Likely Pathogenic· 35 VUS of 46 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.11LOEUF
pLI 1.000
Z-score 4.91
OE 0.00 (0.00–0.11)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
3.74Z-score
OE missense 0.40 (0.34–0.46)
120 obs / 303.5 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.11)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.40 (0.34–0.46)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.87
0≤1.21.6
LoF obs/exp: 0 / 28.1Missense obs/exp: 120 / 303.5Syn Z: 1.13

ClinVar Variant Classifications

46 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic5
VUS35
6
Pathogenic
5
Likely Pathogenic
35
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
1
4
0
5
VUS
0
32
3
0
35
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total03313046

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PRPF19 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

PRPF19-related neurodevelopmental disorder

moderate
ADLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure, Decreased Gene Product Level
Dev. Disorders
G2P ↗
frameshift variantmissense variant

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Spliceosome malfunction causes neurodevelopmental disorders with overlapping features.
Li D et al.·J Clin Invest
2024
Comprehensive analysis of PRPF19 immune infiltrates, DNA methylation, senescence-associated secretory phenotype and ceRNA network in bladder cancer.
Wang Y et al.·Front Immunol
2023
Identification of DNA damage repair-related diagnostic markers for idiopathic pulmonary fibrosis via WGCNA.
Rao X et al.·Comput Biol Chem
2025
PRPF19 facilitates colorectal cancer liver metastasis through activation of the Src-YAP1 pathway via K63-linked ubiquitination of MYL9.
Zhou R et al.·Cell Death Dis
2023
Report of PRPF19 as a novel partner of RARG and the recurrence of interposition-type fusion in variant acute promyelocytic leukemia.
Wu H et al.·Hematol Oncol
2023
Molecular autopsy in maternal-fetal medicine.
Shamseldin HE et al.·Genet Med
2018
Methylome analyses of three glioblastoma cohorts reveal chemotherapy sensitivity markers within DDR genes.
Kessler T et al.·Cancer Med
2020Cohort
Identification of cell senescence molecular subtypes in prediction of the prognosis and immunotherapy of hepatitis B virus-related hepatocellular carcinoma.
Yu X et al.·Front Immunol
2022
Genome-wide DNA copy number analysis in clonally expanded human ovarian cancer cells with distinct invasive/migratory capacities.
Li L et al.·Oncotarget
2017
Evaluation of a partial genome screening of two asthma susceptibility regions using bayesian network based bayesian multilevel analysis of relevance.
Ungvári I et al.·PLoS One
2012
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
AI-aided identification of dual-purpose therapeutic targets PRPF19 and MAPK9 in hepatocellular carcinoma and cellular senescence.
Ren C et al.·NPJ Aging
2025🔓 Open Access
Hub Genes PRPF19 and PPIB: Molecular Pathways and Potential Biomarkers in COPD.
Zhao J et al.·Int J Chron Obstruct Pulmon Dis
2025🔓 Open Access
PRPF19 mediates the proteasomal degradation of VDR to exacerbate ferroptosis in diabetic nephropathy.
He Q et al.·Cell Commun Signal
2025🔓 Open Access
Hypoxia-induced PRPF19 modulates TPT1 alternative splicing to facilitate cisplatin resistance in high-grade serous ovarian cancer.
Wei W et al.·Biochim Biophys Acta Mol Basis Dis
2025
PRPF19 mRNA Encodes a Small Open Reading Frame That Is Important for Viability of Human Cells.
Shepelev NM et al.·Dokl Biochem Biophys
2024🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools