BTBD9 Gene
BTB Domain Containing 9: Genetic Links to Restless Legs Syndrome and Iron Metabolism
Gene Information Card
| Symbol | BTBD9 |
|---|---|
| Full Name | BTB Domain Containing 9 |
| Gene Type | protein-coding |
| Chromosomal Location | 6p21.2 |
| NCBI Gene ID | 114781 ncbi.nlm.nih.gov/gene/114781 |
| Ensembl ID | ENSG00000124588 |
| UniProt ID | Q96Q07 |
| OMIM ID | 611237 |
| HGNC ID | 21228 |
| Aliases | BTB/POZ domain-containing protein 9, FLJ20032 |
Description
BTBD9 encodes a protein containing a BTB (Broad-Complex, Tramtrack, and Bric à brac) domain, which is involved in protein-protein interactions and transcriptional regulation. The gene is located on chromosome 6p21.2 and is widely expressed, with notable levels in the brain and testis. BTBD9 has been strongly associated with Restless Legs Syndrome (RLS) and periodic limb movements in sleep (PLMS), likely through mechanisms involving iron homeostasis and dopaminergic signaling.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Restless Legs Syndrome (RLS) | BTBD9 variants (e.g., rs9357271, rs9296249) are associated with altered iron metabolism in the brain, potentially affecting dopamine synthesis and signaling. | Genome-wide association studies (GWAS) in European populations (PMID: 17637759, 18252227). |
| Periodic Limb Movements in Sleep (PLMS) | Same variants as RLS; BTBD9 risk alleles correlate with increased PLMS index. | GWAS replication studies (PMID: 18252227). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebellum) | 12.5 | Medium |
| Testis | 10.2 | Medium |
| Adrenal gland | 8.1 | Low |
| Skeletal muscle | 6.3 | Low |
| Liver | 4.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 8.9 | Embryonic kidney cells |
| SH-SY5Y | 11.2 | Neuroblastoma cell line |
| K562 | 6.5 | Leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs9357271 | SNP (intronic) | 0.20 (European) | Associated with increased RLS risk; functional effect unknown. |
| rs9296249 | SNP (intronic) | 0.15 (European) | Associated with RLS; may affect BTBD9 expression. |
| rs3923809 | SNP (intronic) | 0.25 (European) | Strongest RLS association; linked to reduced BTBD9 expression in brain. |
Mutation functional classification
Loss of Function (LOF)
Not established; intronic SNPs may reduce BTBD9 expression in brain tissues.
Gain of Function (GOF)
Not reported.
Dominant Negative (DN)
Not reported.
View complete mutation data：
Gene Ontology (GO)
| • protein binding (GO:0005515) | • nucleus (GO:0005634) |
| • cytoplasm (GO:0005737) | • metal ion binding (GO:0046872) |
Pathways
• Iron metabolism and homeostasis (inferred from disease association)
• Dopaminergic signaling (indirect
• via RLS pathophysiology)
Protein Summary
BTBD9 is a 441-amino acid protein containing a BTB domain at the N-terminus. It localizes to both the nucleus and cytoplasm and is thought to participate in protein ubiquitination or transcriptional regulation. The exact biochemical function remains under investigation, but its strong genetic association with Restless Legs Syndrome suggests a role in iron homeostasis and neuronal excitability.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| BTBD9 Knockout HEK293 Cell Line | EDJ-KQ12577 | Human | 114781 | Details Get a Quote |
| BTBD9 Knockout A-549 Cell Line | EDJ-KQ41602 | Human | 114781 | Details Get a Quote |
| BTBD9 Knockout HCT 116 Cell Line | EDJ-KQ41603 | Human | 114781 | Details Get a Quote |
| BTBD9 Knockout HeLa Cell Line | EDJ-KQ41604 | Human | 114781 | Details Get a Quote |
| BTBD9 Knockout SH-SY5Y Cell Line | EDJ-KZ121 | Human | 114781 | Details Get a Quote |
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