Variant Synonymizer: Platform to identify mutations defined in different ways is available now!

VarSy

Over 2,000 gene–disease validation summaries are now available—no login required!

Browse Summaries

SGK2 and Shwachman-Diamond Syndrome

In Shwachman-Diamond syndrome (MONDO_0009833), recent multi-patient studies have reported clonal deletion events in the long arm of chromosome 20 that encompass SGK2 (PMID:27553422) and other imprinted genes. In one study, six SDS cases were identified with del(20q) in bone marrow samples, and a second study confirmed a similar deletion in an additional six SDS patients (PMID:30585299). While no family segregation data is available, these recurrent findings suggest that loss of SGK2 may act as a modifier of the hematological phenotype in SDS, even though mutations in SBDS remain the primary etiologic factor.

Functional assays further support a role for SGK2 in cellular physiology. In heterologous systems, overexpression of SGK2 increased voltage-gated potassium channel activity (PMID:12397388) and stimulated the epithelial sodium channel (PMID:12632189). Although these studies were conducted in non‑disease contexts, the modulation of ion channel activity is consistent with a potential impact on bone marrow function in SDS. Additional evidence, which exceeds the current ClinGen scoring maximum, underscores experimental concordance with the observed clinical phenotype.

Key take‑home: Despite limited genetic evidence, the recurrent loss of SGK2 in SDS patients and its defined role in ion channel regulation provide a basis for its further exploration in diagnostic decision‑making and potential commercial applications.

References

  • Genes, chromosomes & cancer • 2017 • Parental origin of the deletion del(20q) in Shwachman-Diamond patients and loss of the paternally derived allele of the imprinted L3MBTL1 gene PMID:27553422
  • British journal of haematology • 2019 • Shwachman-Diamond syndrome with clonal interstitial deletion of the long arm of chromosome 20 in bone marrow: haematological features, prognosis and genomic instability PMID:30585299
  • Pflugers Archiv : European journal of physiology • 2002 • K+ channel activation by all three isoforms of serum- and glucocorticoid-dependent protein kinase SGK PMID:12397388
  • Pflugers Archiv : European journal of physiology • 2003 • The serine/threonine kinases SGK2 and SGK3 are potent stimulators of the epithelial Na+ channel alpha, beta, gamma-ENaC PMID:12632189

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

Association based on two independent studies documenting del(20q) including SGK2 in 6 SDS cases (PMID:27553422) and 6 additional cases (PMID:30585299) with no segregation data.

Genetic Evidence

Limited

Genetic evidence is confined to clonal deletion events in bone marrow samples from SDS patients without direct segregation or independent mutational events in SGK2.

Functional Evidence

Moderate

Multiple experimental studies demonstrate SGK2’s role in modulating ion channel activity (PMID:12397388; PMID:12632189), supporting its functional relevance even though the data were generated in heterologous systems.