SETD1B
SET Domain Containing 1B, Histone Lysine Methyltransferase
Gene Information Card
| Symbol | SETD1B |
|---|---|
| Full Name | SET Domain Containing 1B |
| Gene Type | Protein coding |
| Chromosomal Location | 12q24.31 |
| NCBI Gene ID | 23067 ncbi.nlm.nih.gov/gene/23067 |
| Ensembl ID | ENSG00000139718 |
| UniProt ID | Q9UPS6 |
| OMIM ID | 611055 |
| HGNC ID | 29187 |
| Aliases | KIAA1076, SET1B, KMT2G, Set1B |
Description
SETD1B encodes a histone methyltransferase that specifically methylates histone H3 at lysine 4 (H3K4), a mark associated with active transcription. It is a core component of the COMPASS complex and plays a critical role in gene activation, development, and neurogenesis. Loss-of-function mutations in SETD1B are linked to intellectual disability, epilepsy, and autism spectrum disorder.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Intellectual developmental disorder with seizures and language delay (IDDSELD) | Heterozygous loss-of-function mutations reduce H3K4 methylation, impairing neuronal gene expression | ClinVar, OMIM |
| Autism spectrum disorder | De novo missense and truncating variants disrupt chromatin regulation | ClinVar, PubMed |
| Epilepsy | SETD1B haploinsufficiency alters synaptic gene transcription, increasing seizure susceptibility | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Testis | 8.3 | Medium |
| Thyroid | 6.1 | Medium |
| Lung | 4.2 | Low |
| Liver | 3.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y | 10.1 | Neuroblastoma cell line |
| HEK293 | 7.8 | Embryonic kidney |
| K562 | 5.4 | Leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.3493C>T (p.Arg1165*) | Nonsense | Rare | Loss of function; truncation of catalytic SET domain |
| c.1672G>A (p.Gly558Arg) | Missense | Rare | Impaired H3K4 methyltransferase activity |
| c.1A>G (p.Met1?) | Start loss | Rare | Complete loss of protein expression |
Mutation functional classification
Loss of Function (LOF)
Most reported SETD1B mutations are loss-of-function, leading to haploinsufficiency and reduced H3K4me3.
Gain of Function (GOF)
No gain-of-function mutations have been reported.
Dominant Negative (DN)
No dominant-negative mechanisms have been described.
View complete mutation data：
Gene Ontology (GO)
| • histone H3-K4 methyltransferase activity | • chromatin binding |
| • nucleus | • regulation of transcription by RNA polymerase II |
| • COMPASS complex |
Pathways
• H3K4 methylation
• Transcriptional regulation by COMPASS
• Chromatin organization
Protein Summary
SETD1B is a 1923-amino acid protein containing an N-terminal RNA recognition motif, a central coiled-coil region, and a C-terminal SET domain responsible for H3K4 methyltransferase activity. It forms a complex with WDR5, RBBP5, ASH2L, and DPY30 to catalyze mono-, di-, and trimethylation of H3K4. The protein is essential for embryonic development and neuronal differentiation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SETD1B Knockout HEK293 Cell Line | EDJ-KQ7807 | Human | 23067 | Details Get a Quote |
| SETD1B Knockout A-549 Cell Line | EDJ-KQ33326 | Human | 23067 | Details Get a Quote |
| SETD1B Knockout HCT 116 Cell Line | EDJ-KQ33327 | Human | 23067 | Details Get a Quote |
| SETD1B Knockout HeLa Cell Line | EDJ-KQ33328 | Human | 23067 | Details Get a Quote |
