SET

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

Basic information

Region (hg38): 9:128683423-128696400

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 (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

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 (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				9	1	10
missense		2	17	3		22
nonsense	2	1				3
start loss						0
frameshift	6	6	2			14
inframe indel			3	1		4
splice donor/acceptor (+/-2bp)	1		1			2
splice region	1		3	4	1	9
non coding			2		4	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)
9-128691221-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)
9-128691989-A-G			Likely pathogenic (Jun 10, 2022)

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

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