SLC9A1
solute carrier family 9 member A1, the group of Protein phosphatase 1 regulatory subunits|Solute carrier family 9
Basic information
Region (hg38): 1:27098809-27166981
Previous symbols: [ "APNH", "NHE1", "NHE-1" ]
Links
Phenotypes
GenCC
Source:
- Lichtenstein-Knorr syndrome (Moderate), mode of inheritance: AR
- Lichtenstein-Knorr syndrome (Limited), mode of inheritance: AR
- Lichtenstein-Knorr syndrome (Supportive), mode of inheritance: AR
- Lichtenstein-Knorr syndrome (Strong), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Spinocerebellar ataxia, autosomal recessive 19 (Lichtenstein-Knorr syndrome) | AR | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Audiologic/Otolaryngologic; Neurologic | 25205112 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (172 variants)
- not_specified (49 variants)
- SLC9A1-related_disorder (12 variants)
- Lichtenstein-Knorr_syndrome (9 variants)
- Inborn_genetic_diseases (2 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC9A1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000003047.5. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 70 | 73 | ||||
| missense | 102 | 106 | ||||
| nonsense | 1 | |||||
| start loss | 0 | |||||
| frameshift | 4 | |||||
| splice donor/acceptor (+/-2bp) | 3 | |||||
| Total | 3 | 3 | 106 | 71 | 4 |
Highest pathogenic variant AF is 0.0000020524637
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| SLC9A1 | protein_coding | protein_coding | ENST00000263980 | 12 | 68167 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.790 | 0.210 | 125730 | 0 | 18 | 125748 | 0.0000716 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.55 | 292 | 520 | 0.562 | 0.0000342 | 5301 |
| Missense in Polyphen | 63 | 188.83 | 0.33363 | 2028 | ||
| Synonymous | 1.66 | 204 | 237 | 0.862 | 0.0000175 | 1724 |
| Loss of Function | 4.22 | 6 | 31.6 | 0.190 | 0.00000179 | 334 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000867 | 0.0000867 |
| Ashkenazi Jewish | 0.000202 | 0.000198 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.000106 | 0.000105 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.000170 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Involved in pH regulation to eliminate acids generated by active metabolism or to counter adverse environmental conditions. Major proton extruding system driven by the inward sodium ion chemical gradient. Plays an important role in signal transduction. {ECO:0000269|PubMed:11350981, ECO:0000269|PubMed:15035633, ECO:0000269|PubMed:8901634}.;
- Disease
- DISEASE: Lichtenstein-Knorr syndrome (LIKNS) [MIM:616291]: An autosomal recessive neurologic disorder characterized by progressive cerebellar ataxia and severe progressive sensorineural hearing loss. {ECO:0000269|PubMed:25205112}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Cardiac muscle contraction - Homo sapiens (human);Bile secretion - Homo sapiens (human);Gastric acid secretion - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Thyroid hormone signaling pathway - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Salivary secretion - Homo sapiens (human);Pancreatic secretion - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Beta-agonist/Beta-blocker Pathway, Pharmacodynamics;Osteoclast Signaling;G Protein Signaling Pathways;Regulation of Actin Cytoskeleton;Hyaluronan uptake and degradation;Hyaluronan metabolism;Metabolism of carbohydrates;Glycosaminoglycan metabolism;Sodium/Proton exchangers;Metabolism;Transport of inorganic cations/anions and amino acids/oligopeptides;SLC-mediated transmembrane transport;Transport of small molecules;ErbB1 downstream signaling;Signaling mediated by p38-alpha and p38-beta;Endothelins;RhoA signaling pathway
(Consensus)
Recessive Scores
- pRec
- 0.460
Intolerance Scores
- loftool
- 0.387
- rvis_EVS
- -1.62
- rvis_percentile_EVS
- 2.93
Haploinsufficiency Scores
- pHI
- 0.417
- hipred
- Y
- hipred_score
- 0.729
- ghis
- 0.540
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.904
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Slc9a1
- Phenotype
- endocrine/exocrine gland phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype;
Gene ontology
- Biological process
- ion transport;cellular sodium ion homeostasis;regulation of pH;response to acidic pH;positive regulation of cardiac muscle hypertrophy;regulation of cardiac muscle contraction by calcium ion signaling;cell migration;maintenance of cell polarity;hyaluronan catabolic process;positive regulation of cell growth;cellular response to insulin stimulus;positive regulation of mitochondrial membrane permeability;response to muscle stretch;sodium ion export across plasma membrane;positive regulation of apoptotic process;negative regulation of apoptotic process;positive regulation of action potential;positive regulation of transcription by RNA polymerase II;protein complex oligomerization;regulation of intracellular pH;regulation of stress fiber assembly;regulation of focal adhesion assembly;regulation of sensory perception of pain;cardiac muscle cell differentiation;cellular response to cold;positive regulation of calcineurin-NFAT signaling cascade;neuron death;cellular response to antibiotic;cellular response to electrical stimulus;cellular response to mechanical stimulus;cellular response to hypoxia;cellular response to acidic pH;potassium ion transmembrane transport;cellular response to epinephrine stimulus;cardiac muscle cell contraction;regulation of cardiac muscle cell membrane potential;regulation of the force of heart contraction by cardiac conduction;sodium ion import across plasma membrane;positive regulation of the force of heart contraction;proton transmembrane transport;positive regulation of calcium:sodium antiporter activity
- Cellular component
- nucleoplasm;cytoplasm;mitochondrion;endoplasmic reticulum;endoplasmic reticulum membrane;plasma membrane;integral component of plasma membrane;focal adhesion;cell surface;intercalated disc;integral component of membrane;basolateral plasma membrane;apical plasma membrane;lamellipodium;T-tubule;membrane raft;perinuclear region of cytoplasm;extracellular exosome;cation-transporting ATPase complex
- Molecular function
- protein binding;calmodulin binding;phosphatidylinositol-4,5-bisphosphate binding;solute:proton antiporter activity;sodium:proton antiporter activity;potassium:proton antiporter activity;protein phosphatase 2B binding;protein binding, bridging;protein-containing complex scaffold activity;calcium-dependent protein binding;sodium:proton antiporter activity involved in regulation of cardiac muscle cell membrane potential