SLC9A9
Solute Carrier Family 9 Member A9
Gene Information Card
| Symbol | SLC9A9 |
|---|---|
| Full Name | Solute Carrier Family 9 Member A9 |
| Gene Type | Protein coding |
| Chromosomal Location | 3q24 |
| NCBI Gene ID | 285195 ncbi.nlm.nih.gov/gene/285195 |
| Ensembl ID | ENSG00000181804 |
| UniProt ID | Q8IVB4 |
| OMIM ID | 608396 |
| HGNC ID | 20653 |
| Aliases | NHE9, MGC138237, MGC138239 |
Description
SLC9A9 encodes a member of the sodium/hydrogen exchanger (NHE) family, specifically NHE9. This protein localizes to recycling endosomes and regulates luminal pH by exchanging extracellular sodium for intracellular protons. Proper endosomal pH is critical for receptor recycling, neurotransmitter vesicle acidification, and synaptic function. Variants in SLC9A9 have been associated with autism spectrum disorder, attention deficit-hyperactivity disorder, and intellectual disability.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autism spectrum disorder | Missense variants impair endosomal pH regulation, altering synaptic protein recycling | PMID: 18342287, ClinVar |
| Attention deficit-hyperactivity disorder | Intronic and missense variants linked to altered dopamine receptor trafficking | PMID: 18342287, OMIM |
| Intellectual disability | Loss-of-function mutations disrupt neuronal pH homeostasis | ClinVar, PMID: 22931937 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 3.2 | Low |
| Testis | 1.8 | Low |
| Kidney | 1.5 | Low |
| Liver | 0.9 | Not detected |
| Heart | 0.6 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 2.1 | Moderate expression |
| HEK293 (embryonic kidney) | 1.0 | Low expression |
| U87MG (glioblastoma) | 0.8 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1192G>A (p.Gly398Arg) | Missense | Rare | Impaired pH regulation, associated with autism |
| c.1663C>T (p.Arg555Trp) | Missense | Rare | Reduced exchanger activity, linked to ADHD |
| c.1765G>A (p.Val589Ile) | Missense | Rare | Uncertain significance |
Mutation functional classification
Loss of Function (LOF)
Missense variants (e.g., p.Gly398Arg) reduce Na+/H+ exchange activity, leading to endosomal alkalinization.
Gain of Function (GOF)
Not reported for SLC9A9.
Dominant Negative (DN)
Not reported for SLC9A9.
View complete mutation data：
Gene Ontology (GO)
| • solute:proton antiporter activity (GO:0015299) | • regulation of pH (GO:0006885) |
| • endosome (GO:0005768) | • apical plasma membrane (GO:0016324) |
| • transmembrane transport (GO:0055085) |
Pathways
• Ion transport by P-type ATPases (Reactome: R-HSA-936837)
• Sodium/proton exchangers (Reactome: R-HSA-425986)
Protein Summary
NHE9 is a 645-amino acid transmembrane protein with 12 predicted membrane-spanning domains. It functions as an electroneutral Na+/H+ antiporter localized to recycling endosomes. By regulating endosomal pH, NHE9 influences the trafficking and recycling of receptors such as transferrin receptor and glutamate receptors. Altered NHE9 activity disrupts synaptic vesicle acidification and neurotransmitter release, contributing to neurodevelopmental phenotypes.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC9A9 Knockout HEK293 Cell Line | EDJ-KQ15289 | Human | 285195 | Details Get a Quote |
| SLC9A9 Knockout HeLa Cell Line | EDJ-KQ48177 | Human | 285195 | Details Get a Quote |
| SLC9A9 Knockout A-549 Cell Line | EDJ-KQ67973 | Human | 285195 | Details Get a Quote |
| SLC9A9 Knockout HCT 116 Cell Line | EDJ-KQ76349 | Human | 285195 | Details Get a Quote |
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