Secreted_frizzled-related_protein_4

SFRP4

SFRP4

Protein-coding gene in the species Homo sapiens

Secreted frizzled-related protein 4 is a protein that in humans is encoded by the SFRP4 gene.[5][6]

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Function

Secreted frizzled-related protein 4 (SFRP4) is a member of the SFRP family that contains a cysteine-rich domain homologous to the putative Wnt-binding site of Frizzled proteins. SFRPs act as soluble modulators of Wnt signaling. The expression of SFRP4 in ventricular myocardium correlates with apoptosis related gene expression.[6]

Biallelic, recessive variants in the SFRP4 gene result in the genetic disorder of bone, Pyle disease,[7] that is characterized by a failure of long bone remodeling with increased fragility. The association between SFRP4 deficiency and Pyle disease has highlighted the importance of SFRP4 in the formation of the bone cortex, and of the importance of bone cortex for the mechanical stability of long bone elements.

SFRP4 is a hub gene in a Type 2 Diabetes-associated gene coexpression module in human islets, and reduces glucose-induced insulin secretion through decreased β-cell exocytosis. Expression and release of SFRP4 from islets is enhanced by interleukin-1β. SFRP4 is elevated in serum several years before clinical diagnosis of Type 2 Diabetes. Individuals who have above-average levels of SFRP4 in the blood are five times more likely to develop diabetes in the next few years than those with below-average levels.[8] SFRP4 concentration seems to correlate with obesity and systemic insulin resistance [9]

References

  1. [1]
    GRCh38: Ensembl release 89: ENSG00000106483 – Ensembl, May 2017
  2. [2]
    GRCm38: Ensembl release 89: ENSMUSG00000021319 – Ensembl, May 2017
  3. [3]
    "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. [4]
    "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. [5]
    Abu-Jawdeh G, Comella N, Tomita Y, Brown LF, Tognazzi K, Sokol SY, Kocher O (April 1999). "Differential expression of frpHE: a novel human stromal protein of the secreted frizzled gene family, during the endometrial cycle and malignancy". Laboratory Investigation; A Journal of Technical Methods and Pathology. 79 (4): 439–447. PMID 10211996.
  6. [6]
    "Entrez Gene: SFRP4 secreted frizzled-related protein 4".
  7. [7]
    Kiper PO, Saito H, Gori F, Unger S, Hesse E, Yamana K, et al. (June 2016). "Cortical-Bone Fragility--Insights from sFRP4 Deficiency in Pyle's Disease". The New England Journal of Medicine. 374 (26): 2553–2562. doi:10.1056/nejmoa1509342. PMC 5070790. PMID 27355534.
  8. [8]
    Mahdi T, Hänzelmann S, Salehi A, Muhammed SJ, Reinbothe TM, Tang Y, et al. (November 2012). "Secreted frizzled-related protein 4 reduces insulin secretion and is overexpressed in type 2 diabetes". Cell Metabolism. 16 (5): 625–633. doi:10.1016/j.cmet.2012.10.009. PMID 23140642.
  9. [9]
    Hörbelt T., Knebel B., Fahlbusch P., Barbosa D., de Wiza D.H., Van de Velde F., Van Nieuwenhove Y., Lapauw B., Thoresen G.H., Al-Hasani H. The adipokine sFRP4 induces insulin resistance and lipogenesis in the liver. Biochim. Biophys. Acta. Mol. Basis Dis. 2019;1865:2671–2684. doi: 10.1016/j.bbadis.2019.07.008

Further reading


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