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
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.

not_provided (272 variants)
Inborn_genetic_diseases (235 variants)
Intellectual_developmental_disorder_with_seizures_and_language_delay (134 variants)
SETD1B-related_disorder (97 variants)
not_specified (22 variants)
Neurodevelopmental_disorder (4 variants)
See_cases (3 variants)
SETD1B-related_neurodevelopmental_disorder (1 variants)
Epilepsy (1 variants)
Neurodevelopmental_delay (1 variants)
SETD1B-associated_disorder (1 variants)
Developmental_delay (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. These statistics are base on transcript: NM_001353345.2. 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			1 clinvar	81 clinvar	11 clinvar	93
missense	11 clinvar	14 clinvar	373 clinvar	77 clinvar	7 clinvar	482
nonsense	15 clinvar	2 clinvar	1 clinvar			18
start loss						0
frameshift	25 clinvar	19 clinvar	3 clinvar			47
splice donor/acceptor (+/-2bp)		3 clinvar	1 clinvar			4
Total	51	38	379	158	18

Highest pathogenic variant AF is 0.0005546786

Loading clinvar variants...

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

loftool
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
essential_gene_gene_trap
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)