SET
Basic information
Region (hg38): 9:128683423-128696400
Links
Phenotypes
GenCC
Source:
- 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:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Intellectual developmental disorder, autosomal dominant 58 | AD | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Craniofacial; Musculoskeletal; Neurologic | 28135719; 28135719; 29688601 |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (6 variants)
- Intellectual disability, autosomal dominant 58 (5 variants)
- Inborn genetic diseases (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 | 10 | |||||
missense | 17 | 22 | ||||
nonsense | 3 | |||||
start loss | 0 | |||||
frameshift | 14 | |||||
inframe indel | 4 | |||||
splice donor/acceptor (+/-2bp) | 2 | |||||
splice region | 1 | 3 | 4 | 1 | 9 | |
non coding | 6 | |||||
Total | 9 | 9 | 25 | 13 | 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) | |||
9-128683925-G-A | Likely benign (Apr 24, 2018) | |||
9-128683960-T-C | Likely benign (Feb 01, 2024) | |||
9-128683961-G-T | Benign (Dec 31, 2019) | |||
9-128689590-C-T | Uncertain significance (May 01, 2022) | |||
9-128689602-AAGTC-A | Uncertain significance (Sep 11, 2023) | |||
9-128689655-G-GAAAAAGAACAGCAAGAAGCGATTGAACACATTGAT | Intellectual disability, autosomal dominant 58 | Uncertain significance (Mar 26, 2020) | ||
9-128689997-G-C | See cases | Uncertain significance (May 10, 2021) | ||
9-128690006-A-T | Intellectual disability, autosomal dominant 58 | Uncertain significance (Dec 11, 2019) | ||
9-128690034-C-T | Benign (Apr 01, 2024) | |||
9-128691167-C-G | Intellectual disability, autosomal dominant 58 | Uncertain significance (Oct 14, 2019) | ||
9-128691171-AAAAG-A | Intellectual disability, autosomal dominant 58 | Pathogenic (Sep 18, 2023) | ||
9-128691198-CAT-C | Intellectual disability, autosomal dominant 58 | Likely pathogenic (Jul 17, 2023) | ||
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) | ||
9-128691235-T-G | Likely benign (Nov 18, 2017) | |||
9-128691841-C-T | Intellectual disability, autosomal dominant 58 | Benign (Jul 15, 2021) | ||
9-128691863-A-AT | Intellectual disability, autosomal dominant 58 | Likely pathogenic (Feb 01, 2023) | ||
9-128691868-C-G | Uncertain significance (Apr 01, 2023) | |||
9-128691909-CAA-C | Pathogenic (Oct 08, 2018) | |||
9-128691943-GA-G | Intellectual disability, autosomal dominant 58 | Likely pathogenic (Jun 07, 2022) | ||
9-128691951-C-T | SET-related disorder | Likely benign (Jan 01, 2024) | ||
9-128691959-TC-T | Likely pathogenic (Oct 23, 2020) | |||
9-128691964-A-T | Intellectual disability, autosomal dominant 58 | Uncertain significance (Nov 23, 2021) | ||
9-128691966-TT-A | Likely pathogenic (Feb 14, 2020) | |||
9-128691970-T-G | Intellectual disability, autosomal dominant 58 | Pathogenic (Apr 29, 2022) |
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
SET | protein_coding | protein_coding | ENST00000372692 | 8 | 12977 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
0.996 | 0.00403 | 0 | 0 | 0 | 0 | 0.00 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | 2.66 | 55 | 145 | 0.379 | 0.00000706 | 1935 |
Missense in Polyphen | 1 | 25.35 | 0.039448 | 446 | ||
Synonymous | -0.598 | 60 | 54.4 | 1.10 | 0.00000304 | 471 |
Loss of Function | 3.74 | 0 | 16.3 | 0.00 | 6.88e-7 | 220 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.00 | 0.00 |
Ashkenazi Jewish | 0.00 | 0.00 |
East Asian | 0.00 | 0.00 |
Finnish | 0.00 | 0.00 |
European (Non-Finnish) | 0.00 | 0.00 |
Middle Eastern | 0.00 | 0.00 |
South Asian | 0.00 | 0.00 |
Other | 0.00 | 0.00 |
dbNSFP
Source:
- 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
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
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