CPSF1

Chr 8AD

cleavage and polyadenylation specific factor 1

Also known as: CPSF160, HSU37012, MYP27, P/cl.18

The CPSF1 protein is the largest subunit of the cleavage and polyadenylation specificity factor complex, which recognizes AAUAAA signals in pre-mRNA and facilitates RNA cleavage and poly(A) tail addition during mRNA processing. Mutations cause autosomal dominant Myopia 27, affecting eye development and retinal ganglion cell projections. The gene is highly constrained against loss-of-function variants (LOEUF 0.54), indicating that such variants are likely pathogenic.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Myopia 27MIM #618827
AD
UniProtMyopia 27, autosomal dominant
0
Active trials
9
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.54
LOEUF
LOF
Mechanism· predicted
Clinical SummaryCPSF1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.54LOEUF
pLI 0.000
Z-score 4.84
OE 0.40 (0.300.54)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.80Z-score
OE missense 0.75 (0.700.79)
719 obs / 963.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.40 (0.300.54)
00.351.4
Missense OE0.75 (0.700.79)
00.61.4
Synonymous OE1.19
01.21.6
LoF obs/exp: 30 / 75.3Missense obs/exp: 719 / 963.5Syn Z: -3.05
DN
0.5082th %ile
GOF
0.4382th %ile
LOF
0.4529th %ile

The Badonyi & Marsh model scores dominant-negative highest, but genomic evidence most strongly supports loss-of-function (haploinsufficiency) as the primary mechanism.

LOF1 literature citation

Literature Evidence

LOFHere we report six rare heterozygous loss-of-function (LoF) variants in CPSF1 that were identified in six of 623 probands with eoHM but none of 2657 probands with other forms of genetic eye diseases; this difference was statistically significant (P = 4.60 × 10-5, Fisher's exact test).PMID:30689892

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CPSF1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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