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GeneBe

SET

SET nuclear proto-oncogene, the group of SET complex|INHAT complex

Basic information

Region (hg38): 9:128683423-128696400

Links

ENSG00000119335NCBI:6418OMIM:600960HGNC:10760Uniprot:Q01105AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • autosomal dominant non-syndromic intellectual disability (Supportive), mode of inheritance: AD
  • intellectual disability, autosomal dominant 58 (Strong), mode of inheritance: AD
  • intellectual disability, autosomal dominant 58 (Strong), mode of inheritance: AD
  • intellectual disability (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Intellectual developmental disorder, autosomal dominant 58ADGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingCraniofacial; Musculoskeletal; Neurologic28135719; 28135719; 29688601

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SET gene.

  • not provided (35 variants)
  • Intellectual disability, autosomal dominant 58 (20 variants)
  • Inborn genetic diseases (7 variants)
  • not specified (1 variants)
  • Intellectual disability (1 variants)
  • Global developmental delay (1 variants)
  • SET-Related Disorder (1 variants)
  • SET-related condition (1 variants)
  • See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SET gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
6
clinvar
1
clinvar
7
missense
2
clinvar
14
clinvar
1
clinvar
17
nonsense
2
clinvar
1
clinvar
3
start loss
0
frameshift
5
clinvar
6
clinvar
2
clinvar
13
inframe indel
3
clinvar
1
clinvar
4
splice donor/acceptor (+/-2bp)
1
clinvar
1
clinvar
2
splice region
1
3
2
1
7
non coding
2
clinvar
4
clinvar
6
Total 8 9 22 8 5

Variants in SET

This is a list of pathogenic ClinVar variants found in the SET region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
9-128683905-A-G Uncertain significance (Oct 04, 2019)1309020
9-128683925-G-A Likely benign (Apr 24, 2018)741914
9-128683960-T-C Likely benign (Feb 01, 2024)3025809
9-128683961-G-T Benign (Dec 31, 2019)774204
9-128689590-C-T Uncertain significance (May 01, 2022)1695268
9-128689602-AAGTC-A Uncertain significance (Sep 11, 2023)1806633
9-128689655-G-GAAAAAGAACAGCAAGAAGCGATTGAACACATTGAT Intellectual disability, autosomal dominant 58 Uncertain significance (Mar 26, 2020)930935
9-128689997-G-C See cases Uncertain significance (May 10, 2021)1690635
9-128690006-A-T Intellectual disability, autosomal dominant 58 Uncertain significance (Dec 11, 2019)1031254
9-128690034-C-T Benign (Oct 01, 2023)1711695
9-128691167-C-G Intellectual disability, autosomal dominant 58 Uncertain significance (Oct 14, 2019)873445
9-128691171-AAAAG-A Intellectual disability, autosomal dominant 58 Pathogenic (Sep 18, 2023)817338
9-128691221-TAGAC-T Inborn genetic diseases • Intellectual disability, autosomal dominant 58 • Global developmental delay • Intellectual disability • SET-Related Disorder Pathogenic/Likely pathogenic (Jan 13, 2023)521454
9-128691235-T-G Likely benign (Nov 18, 2017)711398
9-128691841-C-T Intellectual disability, autosomal dominant 58 Benign (Jul 15, 2021)1332943
9-128691863-A-AT Intellectual disability, autosomal dominant 58 Likely pathogenic (Feb 01, 2023)2505260
9-128691868-C-G Uncertain significance (Apr 01, 2023)2571340
9-128691909-CAA-C Pathogenic (Oct 08, 2018)817064
9-128691943-GA-G Intellectual disability, autosomal dominant 58 Likely pathogenic (Jun 07, 2022)2500283
9-128691951-C-T SET-related condition Likely benign (Jan 01, 2024)3026167
9-128691959-TC-T Likely pathogenic (Oct 23, 2020)987492
9-128691964-A-T Intellectual disability, autosomal dominant 58 Uncertain significance (Nov 23, 2021)1712279
9-128691966-TT-A Likely pathogenic (Feb 14, 2020)916066
9-128691970-T-G Intellectual disability, autosomal dominant 58 Pathogenic (Aug 31, 2018)560206
9-128691989-A-G Likely pathogenic (Jun 10, 2022)1691608

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
SETprotein_codingprotein_codingENST00000372692 812977
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.9960.0040300000.00
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense2.66551450.3790.000007061935
Missense in Polyphen125.350.039448446
Synonymous-0.5986054.41.100.00000304471
Loss of Function3.74016.30.006.88e-7220

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.000.00
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.000.00
Middle Eastern0.000.00
South Asian0.000.00
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: 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. {ECO:0000269|PubMed:11555662, ECO:0000269|PubMed:12628186}.;
Disease
DISEASE: Note=A chromosomal aberration involving SET is found in some cases of acute undifferentiated leukemia (AUL). Translocation t(6;9)(q21;q34.1) with NUP214/CAN.;
Pathway
NOTCH-Ncore;Histone Modifications;granzyme a mediated apoptosis pathway;Metabolism of RNA;HuR (ELAVL1) binds and stabilizes mRNA;Condensation of Prophase Chromosomes;Mitotic Prophase;M Phase;Cell Cycle;Regulation of mRNA stability by proteins that bind AU-rich elements;Cell Cycle, Mitotic;Validated nuclear estrogen receptor alpha network (Consensus)

Recessive Scores

pRec
0.296

Intolerance Scores

loftool
0.435
rvis_EVS
0.3
rvis_percentile_EVS
72.01

Haploinsufficiency Scores

pHI
0.610
hipred
Y
hipred_score
0.825
ghis
0.638

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.993

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Set
Phenotype

Zebrafish Information Network

Gene name
setb
Affected structure
post-vent region
Phenotype tag
abnormal
Phenotype quality
curved

Gene ontology

Biological process
DNA replication;nucleosome assembly;nucleosome disassembly;viral process;negative regulation of phosphoprotein phosphatase activity;negative regulation of histone acetylation;regulation of mRNA stability;negative regulation of neuron apoptotic process;negative regulation of transcription, DNA-templated
Cellular component
nucleus;nucleoplasm;cytoplasm;endoplasmic reticulum;lipid droplet;cytosol;protein-containing complex;perinuclear region of cytoplasm
Molecular function
DNA binding;protein phosphatase inhibitor activity;protein binding;protein phosphatase regulator activity;histone binding