SET

Chr 9q34.11

SET nuclear proto-oncogene

Aliases:: PHAPII, 2PP2A, IPP2A2, TAF-IBETA, IGAAD
MANE:: ENST00000322030.13

OMIM: 600960 ↗NCBI: 6418 ↗Ensembl ↗

Annotations refreshed 9 hours ago.

Predicted protein structure

AlphaFold predicted structure

SET · Q01105

v62025-08-01

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

Mean pLDDT

77.6/ 100

Confident

290 residues

Confidence breakdown

Very high(≥ 90)55%
Confident(70–90)8%
Low(50–70)12%
Very low(< 50)25%

Open interactive 3D viewer

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

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

DDG2P
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Disease associations (Open Targets)

intellectual disability, autosomal dominant 58
0.77
Intellectual disability
0.50
neurodegenerative disease
0.49
hereditary disease
0.49
acute lymphoblastic leukemia
0.39
T-cell acute lymphoblastic leukemia
0.37
autosomal dominant non-syndromic intellectual disability
0.37
Global developmental delay
0.34
acute myeloid leukemia
0.30
B-cell acute lymphoblastic leukemia
0.28

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

Protein function (UniProt)

Protein SET

Multitasking protein, involved in apoptosis, transcription, nucleosome assembly and histone chaperoning. Isoform 2 anti-apoptotic activity is mediated by inhibition of the GZMA-activated DNase, NME1. In the course of cytotoxic T-lymphocyte (CTL)-induced apoptosis, GZMA cleaves SET, disrupting its binding to NME1 and releasing NME1 inhibition. Isoform 1 and isoform 2 are potent inhibitors of protein phosphatase 2A. Isoform 1 and isoform 2 inhibit EP300/CREBBP and PCAF-mediated acetylation of histones (HAT) and nucleosomes, most probably by masking the accessibility of lysines of histones to the acetylases. The predominant target for inhibition is histone H4. HAT inhibition leads to silencing of HAT-dependent transcription and prevents active demethylation of DNA. Both isoforms stimulate DNA replication of the adenovirus genome complexed with viral core proteins; however, isoform 2 specific activity is higher