SGK1
serum/glucocorticoid regulated kinase 1
Basic information
Region (hg38): 6:134169248-134318112
Previous symbols: [ "SGK" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the SGK1 gene is commonly pathogenic or not.
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.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | |||||
| missense | 10 | 13 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 10 | 4 | 1 |
Variants in SGK1
This is a list of pathogenic ClinVar variants found in the SGK1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 6-134170293-G-A | not specified | Uncertain significance (Dec 16, 2023) | ||
| 6-134170319-G-A | Benign (Apr 04, 2018) | |||
| 6-134170333-C-T | not specified | Uncertain significance (Oct 06, 2021) | ||
| 6-134170351-C-T | not specified | Likely benign (Jul 07, 2022) | ||
| 6-134170390-C-G | not specified | Uncertain significance (Mar 01, 2023) | ||
| 6-134170393-C-T | not specified | Uncertain significance (Jan 19, 2024) | ||
| 6-134170402-C-T | not specified | Uncertain significance (Dec 07, 2021) | ||
| 6-134170860-T-C | Multiple myeloma | Likely pathogenic (Aug 31, 2019) | ||
| 6-134171040-C-T | not specified | Uncertain significance (Jan 23, 2023) | ||
| 6-134172286-A-C | not specified | Uncertain significance (Oct 04, 2022) | ||
| 6-134172719-T-C | not specified | Uncertain significance (Aug 12, 2021) | ||
| 6-134173085-G-A | not specified | Uncertain significance (Jun 02, 2023) | ||
| 6-134173523-G-A | not specified | Uncertain significance (Feb 17, 2023) | ||
| 6-134173535-G-A | not specified | Uncertain significance (Jun 10, 2024) | ||
| 6-134174596-A-G | Likely benign (Jul 16, 2018) | |||
| 6-134175584-C-T | Likely benign (Feb 01, 2024) | |||
| 6-134261969-G-C | not specified | Likely benign (Sep 01, 2021) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| SGK1 | protein_coding | protein_coding | ENST00000367858 | 14 | 148867 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.00230 | 0.998 | 125724 | 0 | 24 | 125748 | 0.0000954 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.25 | 236 | 296 | 0.796 | 0.0000159 | 3490 |
| Missense in Polyphen | 38 | 94.264 | 0.40312 | 1135 | ||
| Synonymous | -0.706 | 127 | 117 | 1.08 | 0.00000709 | 965 |
| Loss of Function | 3.32 | 10 | 29.4 | 0.340 | 0.00000153 | 345 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000477 | 0.000379 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000164 | 0.000163 |
| Finnish | 0.0000496 | 0.0000462 |
| European (Non-Finnish) | 0.000115 | 0.0000879 |
| Middle Eastern | 0.000164 | 0.000163 |
| South Asian | 0.0000748 | 0.0000653 |
| Other | 0.000204 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Serine/threonine-protein kinase which is involved in the regulation of a wide variety of ion channels, membrane transporters, cellular enzymes, transcription factors, neuronal excitability, cell growth, proliferation, survival, migration and apoptosis. Plays an important role in cellular stress response. Contributes to regulation of renal Na(+) retention, renal K(+) elimination, salt appetite, gastric acid secretion, intestinal Na(+)/H(+) exchange and nutrient transport, insulin-dependent salt sensitivity of blood pressure, salt sensitivity of peripheral glucose uptake, cardiac repolarization and memory consolidation. Up-regulates Na(+) channels: SCNN1A/ENAC, SCN5A and ASIC1/ACCN2, K(+) channels: KCNJ1/ROMK1, KCNA1-5, KCNQ1-5 and KCNE1, epithelial Ca(2+) channels: TRPV5 and TRPV6, chloride channels: BSND, CLCN2 and CFTR, glutamate transporters: SLC1A3/EAAT1, SLC1A2 /EAAT2, SLC1A1/EAAT3, SLC1A6/EAAT4 and SLC1A7/EAAT5, amino acid transporters: SLC1A5/ASCT2, SLC38A1/SN1 and SLC6A19, creatine transporter: SLC6A8, Na(+)/dicarboxylate cotransporter: SLC13A2/NADC1, Na(+)-dependent phosphate cotransporter: SLC34A2/NAPI-2B, glutamate receptor: GRIK2/GLUR6. Up-regulates carriers: SLC9A3/NHE3, SLC12A1/NKCC2, SLC12A3/NCC, SLC5A3/SMIT, SLC2A1/GLUT1, SLC5A1/SGLT1 and SLC15A2/PEPT2. Regulates enzymes: GSK3A/B, PMM2 and Na(+)/K(+) ATPase, and transcription factors: CTNNB1 and nuclear factor NF-kappa-B. Stimulates sodium transport into epithelial cells by enhancing the stability and expression of SCNN1A/ENAC. This is achieved by phosphorylating the NEDD4L ubiquitin E3 ligase, promoting its interaction with 14-3-3 proteins, thereby preventing it from binding to SCNN1A/ENAC and targeting it for degradation. Regulates store-operated Ca(+2) entry (SOCE) by stimulating ORAI1 and STIM1. Regulates KCNJ1/ROMK1 directly via its phosphorylation or indirectly via increased interaction with SLC9A3R2/NHERF2. Phosphorylates MDM2 and activates MDM2-dependent ubiquitination of p53/TP53. Phosphorylates MAPT/TAU and mediates microtubule depolymerization and neurite formation in hippocampal neurons. Phosphorylates SLC2A4/GLUT4 and up-regulates its activity. Phosphorylates APBB1/FE65 and promotes its localization to the nucleus. Phosphorylates MAPK1/ERK2 and activates it by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2. Phosphorylates FBXW7 and plays an inhibitory role in the NOTCH1 signaling. Phosphorylates FOXO1 resulting in its relocalization from the nucleus to the cytoplasm. Phosphorylates FOXO3, promoting its exit from the nucleus and interference with FOXO3-dependent transcription. Phosphorylates BRAF and MAP3K3/MEKK3 and inhibits their activity. Phosphorylates SLC9A3/NHE3 in response to dexamethasone, resulting in its activation and increased localization at the cell membrane. Phosphorylates CREB1. Necessary for vascular remodeling during angiogenesis. Sustained high levels and activity may contribute to conditions such as hypertension and diabetic nephropathy. Isoform 2 exhibited a greater effect on cell plasma membrane expression of SCNN1A/ENAC and Na(+) transport than isoform 1. {ECO:0000269|PubMed:11154281, ECO:0000269|PubMed:11410590, ECO:0000269|PubMed:11696533, ECO:0000269|PubMed:12397388, ECO:0000269|PubMed:12590200, ECO:0000269|PubMed:12634932, ECO:0000269|PubMed:12650886, ECO:0000269|PubMed:12761204, ECO:0000269|PubMed:12911626, ECO:0000269|PubMed:14623317, ECO:0000269|PubMed:14706641, ECO:0000269|PubMed:15040001, ECO:0000269|PubMed:15044175, ECO:0000269|PubMed:15234985, ECO:0000269|PubMed:15319523, ECO:0000269|PubMed:15496163, ECO:0000269|PubMed:15733869, ECO:0000269|PubMed:15737648, ECO:0000269|PubMed:15845389, ECO:0000269|PubMed:15888551, ECO:0000269|PubMed:16036218, ECO:0000269|PubMed:16443776, ECO:0000269|PubMed:16982696, ECO:0000269|PubMed:17382906, ECO:0000269|PubMed:18005662, ECO:0000269|PubMed:18304449, ECO:0000269|PubMed:18753299, ECO:0000269|PubMed:19447520, ECO:0000269|PubMed:19756449, ECO:0000269|PubMed:20511718, ECO:0000269|PubMed:20730100, ECO:0000269|PubMed:21865597}.;
- Pathway
- PI3K-Akt signaling pathway - Homo sapiens (human);mTOR signaling pathway - Homo sapiens (human);FoxO signaling pathway - Homo sapiens (human);Aldosterone-regulated sodium reabsorption - Homo sapiens (human);Diuretics Pathway, Pharmacodynamics;IGF-Ncore;Follicle Stimulating Hormone (FSH) signaling pathway;MECP2 and Associated Rett Syndrome;PI3K-Akt Signaling Pathway;Insulin Signaling;Gene expression (Transcription);Generic Transcription Pathway;Stimuli-sensing channels;Ion channel transport;RNA Polymerase II Transcription;Transport of small molecules;Glucocorticoid receptor regulatory network;Regulation of TP53 Degradation;Regulation of TP53 Expression and Degradation;IL2;Regulation of TP53 Activity;Class I PI3K signaling events;Transcriptional Regulation by TP53;IL6;mTOR signaling pathway;Insulin Pathway;FoxO family signaling
(Consensus)
Recessive Scores
- pRec
- 0.577
Intolerance Scores
- loftool
- 0.430
- rvis_EVS
- -0.29
- rvis_percentile_EVS
- 33.42
Haploinsufficiency Scores
- pHI
- 0.680
- hipred
- Y
- hipred_score
- 0.825
- ghis
- 0.430
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.999
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Sgk1
- Phenotype
- renal/urinary system phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype;
Gene ontology
- Biological process
- regulation of cell growth;protein phosphorylation;sodium ion transport;apoptotic process;cellular response to DNA damage stimulus;long-term memory;regulation of blood pressure;peptidyl-serine phosphorylation;regulation of cell migration;positive regulation of transporter activity;ion transmembrane transport;intracellular signal transduction;regulation of cell population proliferation;regulation of apoptotic process;neuron projection morphogenesis;regulation of catalytic activity;regulation of DNA-binding transcription factor activity;regulation of gastric acid secretion;renal sodium ion absorption
- Cellular component
- nucleus;cytoplasm;mitochondrion;endoplasmic reticulum membrane;cytosol;plasma membrane;nuclear speck
- Molecular function
- protein serine/threonine kinase activity;protein serine/threonine/tyrosine kinase activity;calcium channel regulator activity;protein binding;ATP binding;potassium channel regulator activity;sodium channel regulator activity;chloride channel regulator activity