SETDB2

SET domain bifurcated histone lysine methyltransferase 2, the group of Lysine methyltransferases|Methyl-CpG binding domain containing|SET domain containing

Basic information

Region (hg38): 13:49444273-49495003

Previous symbols: [ "C13orf4" ]

Links

ENSG00000136169 ∙ NCBI:83852 ∙ OMIM:607865 ∙ HGNC:20263 ∙ Uniprot:Q96T68 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SETDB2 gene.

• Inborn genetic diseases (15 variants)
• not provided (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SETDB2 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				1	1	2
missense			14	1	2	17
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	14	2	3

Variants in SETDB2

This is a list of pathogenic ClinVar variants found in the SETDB2 region.

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

Position	Type	Phenotype	Significance	ClinVar
13-49461138-A-T		not specified	Uncertain significance (Sep 17, 2021)
13-49467915-C-T		not specified	Uncertain significance (Oct 05, 2023)
13-49467916-C-T			Benign (Jun 13, 2018)
13-49476502-C-T		not specified	Uncertain significance (May 18, 2023)
13-49476542-A-C			Likely benign (Apr 01, 2023)
13-49476624-C-A		not specified	Uncertain significance (Aug 10, 2021)
13-49476738-G-A		not specified	Likely benign (Feb 02, 2022)
13-49476778-A-G		not specified	Uncertain significance (May 30, 2023)
13-49476864-G-T		not specified	Uncertain significance (Feb 15, 2023)
13-49476887-A-T		not specified	Uncertain significance (Apr 17, 2023)
13-49477001-T-G		not specified	Uncertain significance (Oct 05, 2023)
13-49480319-A-G		not specified	Uncertain significance (Aug 02, 2021)
13-49480967-T-C		not specified	Uncertain significance (Jan 27, 2022)
13-49481012-A-G		not specified	Uncertain significance (Nov 07, 2023)
13-49482767-A-T			Benign (Dec 31, 2019)
13-49482790-G-A			Benign (Jun 20, 2018)
13-49482939-T-G		not specified	Uncertain significance (Jan 05, 2022)
13-49483555-A-G		not specified	Uncertain significance (Mar 14, 2023)
13-49485648-T-A		not specified	Uncertain significance (Sep 07, 2022)
13-49485649-C-G		not specified	Uncertain significance (Oct 27, 2022)
13-49485711-A-G		not specified	Uncertain significance (Apr 04, 2023)
13-49488541-A-G		not specified	Uncertain significance (Aug 15, 2023)
13-49490879-A-G		not specified	Uncertain significance (Sep 17, 2021)
13-49490916-A-C			Benign (Jun 06, 2017)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SETDB2	protein_coding	protein_coding	ENST00000317257	14	50710

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000232	1.00	125724	0	22	125746	0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.75	265	358	0.740	0.0000170	4751
Missense in Polyphen		73	140.18	0.52075		1864
Synonymous	-0.258	133	129	1.03	0.00000623	1295
Loss of Function	3.58	15	39.2	0.383	0.00000225	478

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000331	0.000326
Finnish	0.00	0.00
European (Non-Finnish)	0.000106	0.000105
Middle Eastern	0.000331	0.000326
South Asian	0.0000660	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Histone methyltransferase involved in left-right axis specification in early development and mitosis. Specifically trimethylates 'Lys-9' of histone H3 (H3K9me3). H3K9me3 is a specific tag for epigenetic transcriptional repression that recruits HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones. Contributes to H3K9me3 in both the interspersed repetitive elements and centromere-associated repeats. Plays a role in chromosome condensation and segregation during mitosis. {ECO:0000269|PubMed:20404330}.
• Pathway: Lysine degradation - Homo sapiens (human);Histone Modifications;PKMTs methylate histone lysines;Chromatin modifying enzymes;Lysine metabolism;Chromatin organization (Consensus)

Recessive Scores

• pRec: 0.0923

Intolerance Scores

• loftool: 0.0881
• rvis_EVS: -0.07
• rvis_percentile_EVS: 48.69

Haploinsufficiency Scores

• pHI: 0.0767
• hipred: N
• hipred_score: 0.273
• ghis: 0.547

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.523

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Setdb2
• Phenotype: immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system phenotype

Zebrafish Information Network

• Gene name: setdb2
• Affected structure: hindbrain neural keel
• Phenotype tag: abnormal
• Phenotype quality: increased width

Gene ontology

• Biological process: mitotic cell cycle;heart looping;chromosome segregation;negative regulation of transcription, DNA-templated;cell division;histone H3-K9 methylation;left/right axis specification
• Cellular component: nucleus;nucleoplasm;chromosome;cytosol
• Molecular function: DNA binding;protein binding;zinc ion binding;histone-lysine N-methyltransferase activity;histone methyltransferase activity (H3-K9 specific)