SGK1

Chr 6

serum/glucocorticoid regulated kinase 1

Also known as: SGK

NCBI Gene: 6446ENSG00000118515UniProt: O00141

This gene encodes a serine/threonine protein kinase that plays an important role in cellular stress response. This kinase activates certain potassium, sodium, and chloride channels, suggesting an involvement in the regulation of processes such as cell survival, neuronal excitability, and renal sodium excretion. High levels of expression of this gene may contribute to conditions such as hypertension and diabetic nephropathy. Several alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jan 2009]

51
ClinVar variants
15
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SGK1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.34) despite low pLI — interpret in context.
📋
ClinVar Variants
15 Pathogenic / Likely Pathogenic· 29 VUS of 51 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.58LOEUF
pLI 0.002
Z-score 3.32
OE 0.34 (0.21–0.58)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.25Z-score
OE missense 0.80 (0.71–0.89)
236 obs / 296.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.34 (0.21–0.58)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.80 (0.71–0.89)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.08
0≤1.21.6
LoF obs/exp: 10 / 29.4Missense obs/exp: 236 / 296.5Syn Z: -0.71

ClinVar Variant Classifications

51 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic1
VUS29
Likely Benign6
Benign1
14
Pathogenic
1
Likely Pathogenic
29
VUS
6
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
14
0
14
Likely Pathogenic
0
1
0
0
1
VUS
0
27
2
0
29
Likely Benign
0
3
2
1
6
Benign
0
0
0
1
1
Total03118251

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SGK1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
📖
GeneReview available — SGK1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Targeted sequencing in DLBCL, molecular subtypes, and outcomes: a Haematological Malignancy Research Network report.
Lacy SE et al.·Blood
2020
Simplified algorithm for genetic subtyping in diffuse large B-cell lymphoma.
Shen R et al.·Signal Transduct Target Ther
2023
Autophagy in the physiological endometrium and cancer.
Devis-Jauregui L et al.·Autophagy
2021Review
Loss of SGK1 supports metastatic colonization in hepatocellular carcinoma by promoting resistance to T cell-mediated immunity.
Zhang Z et al.·J Hepatol
2025
SGK1-Mediated Vascular Smooth Muscle Cell Phenotypic Transformation Promotes Thoracic Aortic Dissection Progression.
Leng S et al.·Arterioscler Thromb Vasc Biol
2025
Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells.
Kleinewietfeld M et al.·Nature
2013
SGK1, autophagy and cancer: an overview.
Ghani MJ·Mol Biol Rep
2022Review
Tumor exosomal circPTBP3 drives gastric cancer peritoneal metastasis via mesothelial-mesenchymal transition.
Dong C et al.·Cell Death Dis
2025
Targeting SGK1 in diabetes.
Lang F et al.·Expert Opin Ther Targets
2009Review
Prdm12 governs an epigenetic checkpoint linking neuroimmune cross-talk to CD8(+) T cell exhaustion-suppressed antitumor immunity.
Liu G et al.·Sci Adv
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools