SET

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

Basic information

Region (hg38): 9:128683424-128696400

Links

ENSG00000119335

∙ NCBI:6418 ∙ OMIM:600960 ∙ HGNC:10760 ∙ Uniprot:Q01105 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

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

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the SET gene.

not_provided (50 variants)
Intellectual_disability,_autosomal_dominant_58 (29 variants)
Inborn_genetic_diseases (14 variants)
SET-related_disorder (8 variants)
not_specified (2 variants)
Dysgerminoma (1 variants)
Global_developmental_delay (1 variants)
Intellectual_disability (1 variants)
See_cases (1 variants)
Hepatocellular_carcinoma (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. These statistics are base on transcript: NM_000003011.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				10 clinvar		10
missense		4 clinvar	33 clinvar	3 clinvar		40
nonsense	2 clinvar	2 clinvar				4
start loss						0
frameshift	9 clinvar	9 clinvar	3 clinvar			21
splice donor/acceptor (+/-2bp)	1 clinvar		1 clinvar			2
Total	12	15	37	13	0

Loading clinvar variants...

GnomAD

Source: gnomAD

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: 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

	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