SETD5: A Key Regulator of Chromatin and Neurodevelopment
Comprehensive gene card for SETD5, including genomic context, expression, mutations, and associated disorders.
Gene Information Card
| Symbol | SETD5 |
|---|---|
| Full Name | SET domain containing 5 |
| Gene Type | Protein coding |
| Chromosomal Location | 3p25.3 |
| NCBI Gene ID | 55209 ncbi.nlm.nih.gov/gene/55209 |
| Ensembl ID | ENSG00000163879 |
| UniProt ID | Q9C0A6 |
| OMIM ID | 615743 |
| HGNC ID | 25509 |
| Aliases | KIAA1753, MRD23 |
Description
SETD5 encodes a SET domain-containing protein that functions as a chromatin regulator, likely involved in transcriptional repression through histone modification. The protein is essential for normal neurodevelopment, and heterozygous loss-of-function mutations cause autosomal dominant intellectual disability syndrome (MRD23). SETD5 is also implicated in autism spectrum disorder and other neurodevelopmental phenotypes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Intellectual developmental disorder 23 (MRD23) | Haploinsufficiency of SETD5 leads to reduced chromatin regulation and altered gene expression during brain development. | OMIM #615743; multiple case reports in ClinVar and literature. |
| Autism spectrum disorder | De novo loss-of-function variants in SETD5 are recurrently found in ASD cohorts, suggesting a causal role. | ClinVar; Iossifov et al., Nature 2014; De Rubeis et al., Nature 2014. |
| Global developmental delay / intellectual disability | Disruption of SETD5 impairs neuronal differentiation and synaptic function. | ClinVar; Grozeva et al., J Med Genet 2014. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 8.5 | Medium |
| Testis | 6.2 | Medium |
| Heart | 4.1 | Low |
| Liver | 2.3 | Low |
| Kidney | 3.0 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 7.8 | Neuronal model; relevant for neurodevelopment studies. |
| HEK293 (embryonic kidney) | 5.4 | Common overexpression system. |
| K562 (leukemia) | 3.2 | Low expression; hematopoietic lineage. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1681C>T (p.Arg561*) | Nonsense | Rare (de novo) | Loss-of-function; premature stop, likely nonsense-mediated decay. |
| c.1090_1091del (p.Leu364Valfs*3) | Frameshift | Rare (de novo) | Loss-of-function; truncated protein. |
| c.1A>G (p.Met1?) | Start loss | Rare (de novo) | Loss-of-function; no translation initiation. |
Mutation functional classification
Loss of Function (LOF)
Primary mechanism: heterozygous loss-of-function (nonsense, frameshift, splice-site, start-loss) leads to haploinsufficiency and neurodevelopmental disorder.
Gain of Function (GOF)
No evidence of gain-of-function mutations in SETD5.
Dominant Negative (DN)
Not reported; current evidence supports haploinsufficiency rather than dominant-negative effect.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Chromatin modifying enzymes
• Transcriptional regulation by SET domain proteins
Protein Summary
SETD5 is a 1442-amino-acid nuclear protein containing a SET domain (residues ~1000-1100) and a coiled-coil region. It is thought to act as a histone methyltransferase or chromatin adaptor, though its exact catalytic activity remains under investigation. The protein is highly expressed in brain and testis, and its disruption leads to altered gene expression profiles critical for neuronal development.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SETD5 Knockout HEK293 Cell Line | EDJ-KQ15235 | Human | 55209 | Details Get a Quote |
| SETD5 Knockout A-549 Cell Line | EDJ-KQ45904 | Human | 55209 | Details Get a Quote |
| SETD5 Knockout HCT 116 Cell Line | EDJ-KQ45905 | Human | 55209 | Details Get a Quote |
| SETD5 Knockout HeLa Cell Line | EDJ-KQ45906 | Human | 55209 | Details Get a Quote |
