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PRPF4

Chr 9AD

pre-mRNA splicing tri-snRNP complex factor PRPF4

Also known as: HPRP4, HPRP4P, PRP4, Prp4p, RP70, SNRNP60

NCBI Gene: 9128 ENSG00000136875 UniProt: O43172

The protein encoded by this gene is part of a heteromeric complex that binds U4, U5, and U6 small nuclear RNAs and is involved in pre-mRNA splicing. The encoded protein also is a mitotic checkpoint protein and a regulator of chemoresistance in human ovarian cancer. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2016]

Primary Disease Associations & Inheritance

Retinitis pigmentosa 70MIM #615922

AD

426

ClinVar variants

28

Pathogenic / LP

1.00

pLI score· haploinsufficient

0

Active trials

Clinical Summary— PRPF4

⚡

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

28 Pathogenic / Likely Pathogenic· 162 VUS of 426 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient

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.

0.23LOEUF

pLI 0.999

Z-score 4.94

OE 0.09 (0.04–0.23)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

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.

1.99Z-score

OE missense 0.68 (0.61–0.76)

210 obs / 308.5 exp

Tolerant

Mild missense constraint

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.0.09 (0.04–0.23)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.68 (0.61–0.76)

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.0.96

0≤1.21.6

LoF obs/exp: 3 / 34.2Missense obs/exp: 210 / 308.5Syn Z: 0.33

ClinVar Variant Classifications

426 submitted variants in ClinVar

Classification Summary

Pathogenic24

Likely Pathogenic4

VUS162

Likely Benign114

Benign7

24

Pathogenic

4

Likely Pathogenic

162

VUS

114

Likely Benign

7

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	24	0	24
Likely Pathogenic	0	1	3	0	4
VUS	3	122	35	2	162
Likely Benign	0	2	61	51	114
Benign	0	0	6	1	7
Total	3	125	129	54	311

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

View in ClinVar →

Protein Context — Lollipop Plot

PRPF4 · protein map & ClinVar variants

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

Gene2Phenotype Curations

PRPF4-related retinitis pigmentosa

definitive

ADLoss Of FunctionAbsent Gene Product

Eye

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

PRE-mRNA-PROCESSING FACTOR 4; PRPF4

MIM #607795 · *

Retinitis pigmentosa 70

Molecular basis of disorder known

Autosomal dominant

External Resources

Links to major genomics databases and tools

Variant Interpretation

Variant interpretation & classification platform

Franklin by Genoox

AI-powered variant curation and clinical analysis

Genomic literature search for variants and genes

ACMG/AMP variant classification tool

Population Databases

Population allele frequencies & constraint metrics

Genomic variants and phenotypes in rare disease patients

Clinical variant interpretations from submitters worldwide

Short genetic variation database

Gene Resources

Gene annotation, transcripts & comparative genomics

Comprehensive gene information and references

Protein sequence, structure and function

Online Mendelian Inheritance in Man

Human gene compendium

Gene expression across human tissues

Expert Curation

Expert-curated gene-disease validity

Gene Curation Coalition — multi-curator classifications

Rare disease encyclopedia and gene-disease associations

Autism-gene association scoring (SFARI)

Gene panels for rare disease diagnostics (Genomics England)

Leiden Open Variation Database — variant listings

Expert-authored summaries of heritable conditions (NCBI)

Clinical Literature

Landmark / reviewRecent case evidence

Key Publications

Landmark & review papers · by relevance

PubMed

Identification of a PRPF4 loss-of-function variant that abrogates U4/U6.U5 tri-snRNP integration and is associated with retinitis pigmentosa.

Linder B et al.·PLoS One

2014

Combining a prioritization strategy and functional studies nominates 5'UTR variants underlying inherited retinal disease.

Dueñas Rey A et al.·Genome Med

2024Functional

PRPF4 mutations cause autosomal dominant retinitis pigmentosa.

Chen X et al.·Hum Mol Genet

2014

NHP2 and PRPF4 are hub genes associated with the prognosis of colorectal cancer.

Li N et al.·BMC Cancer

2025

Estimating genetic load from 5000 Chinese exomes.

Du X et al.·J Genet Genomics

2026

Mutational screening of splicing factor genes in cases with autosomal dominant retinitis pigmentosa.

Benaglio P et al.·Mol Vis

2014Cohort

Mutations in spliceosomal proteins and retina degeneration.

Růžičková Š et al.·RNA Biol

2017Review

Pathogenic genes related to the progression of actinic keratoses to cutaneous squamous cell carcinoma.

Zhang L et al.·Int J Dermatol

2018

Clinical and whole exome sequencing findings in children from Yunnan Yi minority ethnic group with retinitis pigmentosa: two case reports.

Xiao YS et al.·J Med Case Rep

2023Case report

PTBP3 Associated With 9q32 Locus Is a Candidate Gene for Nager Syndrome.

Gonzalez JA et al.·Birth Defects Res

2025

Top 10 resultsSearch PubMed ↗

Recent Gene-Specific Literature

Gene in title · MEDLINE · newest first

Europe PMC

Prpf4 sequentially regulates the expansion and maturation of erythrocyte through distinct mechanisms.

Deng Z et al.·Cell Death Discov

2025🔓 Open AccessFunctional

PRPF4 Knockdown Suppresses Glioblastoma Progression via the p38 MAPK and ERK Signaling Pathways.

Kim W et al.·Anticancer Res

2025

Suppression of PRPF4 regulates pluripotency, proliferation, and differentiation in mouse embryonic stem cells.

Park S et al.·Cell Biochem Funct

2019Functional

PRPF4 is a novel therapeutic target for the treatment of breast cancer by influencing growth, migration, invasion, and apoptosis of breast cancer cells via p38 MAPK signaling pathway.

Park S et al.·Mol Cell Probes

2019

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

Variant Interpretation

Variant interpretation & classification platform

Franklin by Genoox

AI-powered variant curation and clinical analysis

Genomic literature search for variants and genes

ACMG/AMP variant classification tool

Population Databases

Population allele frequencies & constraint metrics

Genomic variants and phenotypes in rare disease patients

Clinical variant interpretations from submitters worldwide

Short genetic variation database

Gene Resources

Gene annotation, transcripts & comparative genomics

Comprehensive gene information and references

Protein sequence, structure and function

Online Mendelian Inheritance in Man

Human gene compendium

Gene expression across human tissues

Expert Curation

Expert-curated gene-disease validity

Gene Curation Coalition — multi-curator classifications

Rare disease encyclopedia and gene-disease associations

Autism-gene association scoring (SFARI)

Gene panels for rare disease diagnostics (Genomics England)

Leiden Open Variation Database — variant listings

Expert-authored summaries of heritable conditions (NCBI)