PRPF8

Chr 17

pre-mRNA processing factor 8

Also known as: HPRP8, PRP8, PRPC8, RP13, SNRNP220

NCBI Gene: 10594ENSG00000174231UniProt: Q6P2Q9

Pre-mRNA splicing occurs in 2 sequential transesterification steps. The protein encoded by this gene is a component of both U2- and U12-dependent spliceosomes, and found to be essential for the catalytic step II in pre-mRNA splicing process. It contains several WD repeats, which function in protein-protein interactions. This protein has a sequence similarity to yeast Prp8 protein. This gene is a candidate gene for autosomal dominant retinitis pigmentosa. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

UniProtRetinitis pigmentosa 13
509
ClinVar variants
39
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— PRPF8
🧬
Gene-Disease Validity (ClinGen)
PRPF8-related retinopathy · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
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
39 Pathogenic / Likely Pathogenic· 239 VUS of 509 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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.
0.18LOEUF
pLI 1.000
Z-score 9.10
OE 0.11 (0.07–0.18)
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.
8.28Z-score
OE missense 0.35 (0.33–0.38)
458 obs / 1297.8 exp
Constrained

Extremely missense-constrained (top ~0.01%)

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.0.11 (0.07–0.18)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.35 (0.33–0.38)
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.1.25
0≤1.21.6
LoF obs/exp: 14 / 122.8Missense obs/exp: 458 / 1297.8Syn Z: -4.38

ClinVar Variant Classifications

509 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic28
Likely Pathogenic11
VUS239
Likely Benign212
Benign14
Conflicting5
28
Pathogenic
11
Likely Pathogenic
239
VUS
212
Likely Benign
14
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
8
12
0
28
Likely Pathogenic
1
9
1
0
11
VUS
3
201
29
6
239
Likely Benign
0
3
71
138
212
Benign
0
0
8
6
14
Conflicting
—5
Total12221121150509

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

View in ClinVar →

Protein Context — Lollipop Plot

PRPF8 · protein map & ClinVar variants

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

Gene2Phenotype Curations

PRPF8-related developmental disorder

moderate
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

PRPF8-related glaucoma

limited
ADUndeterminedAltered Gene Product Structure
Eye
G2P ↗
missense variantinframe deletioninframe insertion

PRPF8-related retinitis pigmentosa

definitive
ADUndeterminedAltered Gene Product Structure
Eye
G2P ↗
missense variantinframe deletioninframe insertion

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — PRPF8
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Heterozygous variants in PRPF8 are associated with neurodevelopmental disorders.
O'Grady L et al.·Am J Med Genet A
2022Case report
Altered splicing machinery in lung carcinoids unveils NOVA1, PRPF8 and SRSF10 as novel candidates to understand tumor biology and expand biomarker discovery.
Blázquez-Encinas R et al.·J Transl Med
2023
Variability in clinical phenotypes of PRPF8-linked autosomal dominant retinitis pigmentosa correlates with differential PRPF8/SNRNP200 interactions.
Escher P et al.·Ophthalmic Genet
2018
Reporting a Homozygous Case of Neurodevelopmental Disorder Associated With a Novel PRPF8 Variant.
Mirinezhad MR et al.·Mol Genet Genomic Med
2025Case report
Extending the phenotypic spectrum of PRPF8, PRPH2, RP1 and RPGR, and the genotypic spectrum of early-onset severe retinal dystrophy.
Georgiou M et al.·Orphanet J Rare Dis
2021
PRPF8 defects cause missplicing in myeloid malignancies.
Kurtovic-Kozaric A et al.·Leukemia
2015
The splicing machinery is dysregulated and represents a therapeutic vulnerability in breast cancer.
Hermán-Sánchez N et al.·Cell Mol Life Sci
2024
Deep clinical and genetic analysis of 17p13.3 region: 38 pediatric patients diagnosed using next-generation sequencing and literature review.
Ji X et al.·BMC Med Genomics
2025Review
Variants in the PRPF8 Gene are Associated with Glaucoma.
Micheal S et al.·Mol Neurobiol
2018
Mutations in spliceosomal proteins and retina degeneration.
Růžičková Š et al.·RNA Biol
2017Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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