CPSF3

Chr 2p25.1

cleavage and polyadenylation specific factor 3

Aliases:: CPSF-73, CPSF73, YSH1
MANE:: ENST00000238112.8

OMIM: 606029 ↗NCBI: 51692 ↗Ensembl ↗

Annotations refreshed 10 hours ago.

Predicted protein structure

AlphaFold predicted structure

CPSF3 · Q9UKF6

v62025-08-01

Predicted Aligned Error matrix for CPSF3 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

90.2/ 100

Very high

684 residues

Confidence breakdown

Very high(≥ 90)65%
Confident(70–90)30%
Low(50–70)4%
Very low(< 50)2%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

DDG2P
BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy
BIALLELIC, autosomal or pseudoautosomal
Intellectual disability
BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

neurodevelopmental disorder with microcephaly, hypotonia, nystagmus, and seizures
0.60
neurodegenerative disease
0.53
neurodevelopmental disorder with hypotonia, microcephaly, and seizures
0.42
complex neurodevelopmental disorder
0.37
dengue disease
0.37
hepatocellular carcinoma
0.10
breast cancer
0.09
diabetic ketoacidosis
0.08
breast carcinoma
0.08
colorectal carcinoma
0.07

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Cleavage and polyadenylation specificity factor subunit 3

Component of the cleavage and polyadenylation specificity factor (CPSF) complex that plays a key role in pre-mRNA 3'-end formation, recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition. Has endonuclease activity, and functions as an mRNA 3'-end-processing endonuclease (PubMed:30507380). Also involved in the histone 3'-end pre-mRNA processing (PubMed:30507380). U7 snRNP-dependent protein that induces both the 3'-endoribonucleolytic cleavage of histone pre-mRNAs and acts as a 5' to 3' exonuclease for degrading the subsequent downstream cleavage product (DCP) of mature histone mRNAs. Cleavage occurs after the 5'-ACCCA-3' sequence in the histone pre-mRNA leaving a 3'hydroxyl group on the upstream fragment containing the stem loop (SL) and 5' phosphate on the downstream cleavage product (DCP) starting with CU nucleotides. The U7-dependent 5' to 3' exonuclease activity is processive and degrades the DCP RNA substrate even after complete removal of the U7-binding site. Binds to the downstream cleavage product (DCP) of histone pre-mRNAs and the cleaved DCP RNA substrate in a U7 snRNP dependent manner. Required for entering/progressing through S-phase of the cell cycle (PubMed:30507380). Required for the selective processing of microRNAs (miRNAs) during embryonic stem cell differentiation via its interaction with ISY1 (By similarity). Required for the biogenesis of all miRNAs from the pri-miR-17-92 primary transcript except miR-92a (By similarity). Only required for the biogenesis of miR-290 and miR-96 from the pri-miR-290-295 and pri-miR-96-183 primary transcripts, respectively (By similarity)