PRPF19

Chr 11

pre-mRNA processing factor 19

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

NCBI Gene: 27339 ENSG00000110107 UniProt: Q9UMS4 OMIM: 608330

The PRPF19 protein functions as a ubiquitin ligase that is essential for pre-mRNA splicing as a core component of the spliceosome and also participates in DNA damage response pathways. Mutations cause neurodevelopmental disorders with intellectual disability and other systemic features, following an autosomal dominant inheritance pattern. This gene is highly intolerant to loss-of-function variants, indicating that maintaining proper protein levels is critical for normal cellular function.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.11

LOEUF· LoF intol.

LOF

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

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?

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?

LoF OE?0.00 (0.00–0.11)

0≤0.351.4

Missense OE?0.40 (0.34–0.46)

0≤0.61.4

Synonymous OE?0.87

0≤1.21.6

LoF obs/exp: 0 / 28.1Missense obs/exp: 120 / 303.5Syn Z: 1.13

Background carrier burden — how many people carry a rare variant somewhere in PRPF19?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 320

343 rare PASS variants

Rare truncating (LoF)

1 in 33,000

5 rare PASS variants

Rare synonymous (reference)

1 in 210

242 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PRPF19. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 400	≈ 1 in 280,000
South Asian	~43k	1 in 190	≈ 1 in 43,000
Remaining (unassigned)	~30k	1 in 220	none seen
European (Finnish)	~27k	1 in 2,000	none seen
Admixed American	~22k	1 in 220	none seen
African / African American	~21k	1 in 230	≈ 1 in 21,000
East Asian	~20k	1 in 170	none seen
Ashkenazi Jewish	~13k	≈ 1 in 13,000	1 in 1,700
Middle Eastern	~2,884	≈ 1 in 2,900	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 16 coding exons well covered in gnomAD exomes and genomes.? see exons ↓