SLC9B2
protein-codingsolute carrier family 9 member B2, the group of Solute carrier family 9
Gene summary
Sodium hydrogen antiporters, such as NHEDC2, convert the proton motive force established by the respiratory chain or the F1F0 mitochondrial ATPase into sodium gradients that drive other energy-requiring processes, transduce environmental signals into cell responses, or function in drug efflux (Xiang et al., 2007 [PubMed 18000046]).[supplied by OMIM, Mar 2008]
- NHEDC2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~66.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SLC9B2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_178833.7. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 2 | 3 | |||
| missense | 82 | 1 | 83 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 85 | 0 | 3 | 88 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_849155.2 | 11 | MANE Select | |
| Ensembl | ENSP00000378265.3 | 11 | MANE Select | |
| RefSeq | NP_001287683.1 | 10 | Standard | |
| RefSeq | NP_001287685.1 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Stimuli-sensing channels
- Ion channel transport
- Transport of small molecules
Biological Process
- sodium ion transport
- flagellated sperm motility
- ion transmembrane transport
- sodium ion transmembrane transport
- regulation of insulin secretion involved in cellular response to glucose stimulus
Molecular Function
- monovalent cation:proton antiporter activity
- lithium:proton antiporter activity
- sodium:proton antiporter activity
- identical protein binding
Cellular Component
- mitochondrial inner membrane
- plasma membrane
- endosome membrane
- integral component of membrane
- basolateral plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000394785
- Coding exons
- 11
- Length
- 65962
- Individuals with no LoFs
- 125688
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 60
- Defined
- 125748
- p
- 0.000239
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0531 | 284 | 281 | 1.01 | 0.0000131 | 3446 |
| Missense (PolyPhen) | 109 | 94.316 | 1.1557 | 1191 | ||
| Synonymous | 0.876 | 91 | 102 | 0.890 | 0.00000518 | 1124 |
| Loss of Function | 2.12 | 12 | 23.0 | 0.522 | 0.00000107 | 293 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.00070 | 0.00061 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00039 | 0.00038 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00020 | 0.00019 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Na(+)/H(+) antiporter that extrudes Na(+) or Li(+) in exchange for external protons across the membrane (PubMed:18000046, PubMed:28154142, PubMed:22948142, PubMed:18508966). Contributes to the regulation of intracellular pH, sodium homeostasis, and cell volume. Plays an important role for insulin secretion and clathrin-mediated endocytosis in beta- cells (By similarity). Involved in sperm motility and fertility (By similarity). It is controversial whether SLC9B2 plays a role in osteoclast differentiation or not (By similarity). {ECO:0000250|UniProtKB:Q5BKR2, ECO:0000269|PubMed:18000046, ECO:0000269|PubMed:18508966, ECO:0000269|PubMed:22948142, ECO:0000269|PubMed:28154142}.;
Recessive Scores
- pRec
- 0.106
Intolerance Scores
- RVIS EVS
- 0.58
- RVIS percentile EVS
- 82.25
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |