PRPF8

Chr 17AD

pre-mRNA processing factor 8

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

NCBI Gene: 10594 ENSG00000174231 UniProt: Q6P2Q9 OMIM: 607300

The protein is a core component of both U2- and U12-type spliceosomes that functions as a scaffold positioning snRNAs at splice sites and mediating ordered assembly of spliceosomal proteins essential for pre-mRNA splicing. Mutations cause autosomal dominant retinitis pigmentosa 13, affecting retinal function and vision. The gene is highly constrained against loss-of-function variants (pLI ~1.0, LOEUF 0.178), indicating that complete loss of protein function is likely incompatible with normal development.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

LOFmechanismADLOEUF 0.181 OMIM phenotype

Clinical Summary— PRPF8

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Gene-Disease Validity (ClinGen)

PRPF8-related retinopathy · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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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.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint

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

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

LoF OE0.11 (0.07–0.18)

0≤0.351.4

Missense OE0.35 (0.33–0.38)

0≤0.61.4

Synonymous OE1.25

0≤1.21.6

LoF obs/exp: 14 / 122.8Missense obs/exp: 458 / 1297.8Syn Z: -4.38

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

moderatePRPF8-related developmental disorderLOFAD

limitedPRPF8-related glaucomaOTHERAD

definitivePRPF8-related retinitis pigmentosaOTHERAD

0.3395th %ile

GOF

0.1999th %ile

LOF

0.77top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · LOEUF 0.18

Literature Evidence

LOFTo explain the incomplete penetrance in several families linked to this RP11 locus, it has been suggested that a high expression of wild-type allele may be able to compensate for the presumable nonfunctioning mutant allele. 10 22 Thus, these mutations seem to induce a pathogenic mechanism by haploinPMID:34395430

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.