SETD1B

SET domain containing 1B, histone lysine methyltransferase, the group of Lysine methyltransferases|RNA binding motif containing|SET domain containing

Basic information

Region (hg38): 12:121804009-121832656

Links

ENSG00000139718 ∙ NCBI:23067 ∙ OMIM:611055 ∙ HGNC:29187 ∙ Uniprot:Q9UPS6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual developmental disorder with seizures and language delay (Moderate), mode of inheritance: AD
• intellectual developmental disorder with seizures and language delay (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder with seizures and language delay	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	29322246; 31110234; 32546566

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SETD1B gene.

• Intellectual developmental disorder with seizures and language delay (14 variants)
• not provided (10 variants)
• Inborn genetic diseases (3 variants)
• SETD1B-related disorder (1 variants)
• Neurodevelopmental disorder (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 SETD1B 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	68	11	80
missense	4	9	218	59	5	295
nonsense	6					6
start loss						0
frameshift	16	15	2			33
inframe indel		1	6	4		11
splice donor/acceptor (+/-2bp)		3	1			4
splice region			2		1	3
non coding				1	2	3
Total	26	28	228	132	18

Highest pathogenic variant AF is 0.00000713

Variants in SETD1B

This is a list of pathogenic ClinVar variants found in the SETD1B region.

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

Position	Type	Phenotype	Significance	ClinVar
12-121804732-A-G		SETD1B-related disorder	Likely benign (Sep 05, 2019)
12-121804749-TCACCCCCCC-T		Intellectual developmental disorder with seizures and language delay	Uncertain significance (-)
12-121804751-A-AC		Neurodevelopmental disorder • Inborn genetic diseases • Intellectual developmental disorder with seizures and language delay • Neoplasm	Pathogenic (Oct 08, 2024)
12-121804754-C-G		Intellectual developmental disorder with seizures and language delay • Inborn genetic diseases	Uncertain significance (Oct 29, 2024)
12-121804757-C-T		Intellectual developmental disorder with seizures and language delay	Uncertain significance (May 06, 2021)
12-121804760-A-C		not specified	Benign/Likely benign (Mar 28, 2024)
12-121804761-C-G		SETD1B-related disorder	Uncertain significance (Oct 18, 2022)
12-121804770-C-G		Inborn genetic diseases	Benign (Mar 15, 2022)
12-121804799-C-A		Intellectual developmental disorder with seizures and language delay	Pathogenic (May 12, 2022)
12-121804826-G-A		Intellectual developmental disorder with seizures and language delay	Uncertain significance (Nov 05, 2022)
12-121804842-G-A		Inborn genetic diseases	Likely benign (Jan 27, 2022)
12-121804867-C-T		Inborn genetic diseases	Uncertain significance (Mar 20, 2024)
12-121804876-CTG-C			Likely pathogenic (Jul 01, 2022)
12-121804881-C-T			Likely benign (Jul 01, 2022)
12-121804898-A-G			Uncertain significance (Jun 24, 2024)
12-121805112-C-T			Benign (Mar 01, 2022)
12-121805128-A-G		Intellectual developmental disorder with seizures and language delay	Uncertain significance (Apr 26, 2022)
12-121805153-TC-T		Intellectual developmental disorder with seizures and language delay	Pathogenic (Dec 31, 2022)
12-121805168-G-A		SETD1B-related disorder	Benign (Aug 01, 2022)
12-121805199-TC-AA			Uncertain significance (Jun 24, 2020)
12-121805218-T-C		Intellectual developmental disorder with seizures and language delay	Uncertain significance (Nov 01, 2021)
12-121805845-TCT-A		Intellectual developmental disorder with seizures and language delay	Pathogenic (Apr 14, 2023)
12-121805847-T-TACGTGGGA		Intellectual developmental disorder with seizures and language delay	Pathogenic (Oct 18, 2022)
12-121805867-G-A			Likely benign (May 01, 2022)
12-121805869-A-C		Inborn genetic diseases	Uncertain significance (May 23, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SETD1B	protein_coding	protein_coding	ENST00000267197	17	28477

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	1.86e-7	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.67	706	1.15e+3	0.613	0.0000769	12303
Missense in Polyphen		91	187.96	0.48414		1927
Synonymous	-1.06	551	520	1.06	0.0000389	4098
Loss of Function	6.74	4	60.6	0.0660	0.00000343	714

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: Histone methyltransferase that specifically methylates 'Lys-4' of histone H3, when part of the SET1 histone methyltransferase (HMT) complex, but not if the neighboring 'Lys- 9' residue is already methylated. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. The non-overlapping localization with SETD1A suggests that SETD1A and SETD1B make non-redundant contributions to the epigenetic control of chromatin structure and gene expression. Specifically tri-methylates 'Lys-4' of histone H3 in vitro.
• Pathway: Lysine degradation - Homo sapiens (human);Histone Modifications;Gene expression (Transcription);Generic Transcription Pathway;PKMTs methylate histone lysines;RNA Polymerase II Transcription;RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function;Chromatin modifying enzymes;Chromatin organization;Transcriptional regulation by RUNX1 (Consensus)

Recessive Scores

• pRec: 0.106

Intolerance Scores

• rvis_EVS: 0.2
• rvis_percentile_EVS: 67.43

Haploinsufficiency Scores

• pHI: 0.222
• hipred: Y
• hipred_score: 0.672
• ghis: 0.478

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.975

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Setd1b
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); embryo phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: histone H3-K4 methylation
• Cellular component: nucleoplasm;chromosome;cytosol;nuclear speck;histone methyltransferase complex;Set1C/COMPASS complex
• Molecular function: RNA binding;protein binding;histone-lysine N-methyltransferase activity;histone methyltransferase activity (H3-K4 specific)