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URL of this page: https://medlineplus.gov/genetics/gene/serping1/

SERPING1 gene

serpin family G member 1

Normal Function

The SERPING1 gene provides instructions for making a protein called C1 inhibitor (C1-INH), which is a type of serine protease inhibitor (serpin). Serpins help control several types of chemical reactions by blocking the activity of certain proteins. C1-INH is important for controlling a range of processes involved in maintaining blood vessels, including inflammation. Inflammation is a normal body response to infection, irritation, or injury.

C1-INH blocks the activity of several proteins in the blood, including plasma kallikrein and the activated form of factor XII (called factor XIIa). These two proteins are involved in the production of bradykinin. Bradykinin is a protein fragment (peptide) that promotes inflammation by allowing fluids to leak through blood vessel walls into body tissues (vascular permeability). C1-INH attaches (binds) to plasma kallikrein and factor XIIa, which prevents them from completing any further reactions. These proteins are cleared from the bloodstream once they are bound to C1-INH.

Health Conditions Related to Genetic Changes

Hereditary angioedema

Hundreds of variants (also called mutations) in the SERPING1 gene have been found to cause hereditary angioedema, which is a disorder characterized by recurrent episodes of severe swelling (angioedema). Variants in the SERPING1 gene cause a form of the condition known as hereditary angioedema due to C1-INH deficiency. Hereditary angioedema due to C1-INH deficiency is further divided into two types: type I occurs when the C1-INH protein levels are low, and type II occurs when C1-INH is not functioning correctly. 

The variants that cause hereditary angioedema due to C1-INH deficiency type I occur throughout the gene and lead to reduced levels of C1-INH in the blood. The variants that cause hereditary angioedema due to C1-INH deficiency type II usually occur in a specific region of the gene called exon 8. These variants lead to the production of a C1-INH that functions abnormally. 

Without the proper levels of functional C1-INH, the activity of plasma kallikrein and factor XIIa cannot be blocked, and excessive amounts of bradykinin are produced. Excess fluids leak through blood vessel walls and accumulate in body tissues, leading to the recurrent episodes of swelling seen in individuals with hereditary angioedema due to C1-INH deficiency.

More About This Health Condition

Other Names for This Gene

  • C1-INH
  • C1IN
  • C1INH
  • C1NH
  • complement component 1 inhibitor
  • IC1_HUMAN
  • plasma protease C1 inhibitor
  • serine/cysteine proteinase inhibitor clade G member 1
  • serpin peptidase inhibitor, clade G (C1 inhibitor), member 1

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases

References

  • Busse PJ, Christiansen SC, Riedl MA, Banerji A, Bernstein JA, Castaldo AJ, Craig T, Davis-Lorton M, Frank MM, Li HH, Lumry WR, Zuraw BL. US HAEA Medical Advisory Board 2020 Guidelines for the Management of Hereditary Angioedema. J Allergy Clin Immunol Pract. 2021 Jan;9(1):132-150.e3. doi: 10.1016/j.jaip.2020.08.046. Epub 2020 Sep 6. Citation on PubMed
  • Cugno M, Zanichelli A, Foieni F, Caccia S, Cicardi M. C1-inhibitor deficiency and angioedema: molecular mechanisms and clinical progress. Trends Mol Med. 2009 Feb;15(2):69-78. doi: 10.1016/j.molmed.2008.12.001. Epub 2009 Jan 21. Citation on PubMed
  • Gosswein T, Kocot A, Emmert G, Kreuz W, Martinez-Saguer I, Aygoren-Pursun E, Rusicke E, Bork K, Oldenburg J, Muller CR. Mutational spectrum of the C1INH (SERPING1) gene in patients with hereditary angioedema. Cytogenet Genome Res. 2008;121(3-4):181-8. doi: 10.1159/000138883. Epub 2008 Aug 28. Citation on PubMed
  • Pappalardo E, Caccia S, Suffritti C, Tordai A, Zingale LC, Cicardi M. Mutation screening of C1 inhibitor gene in 108 unrelated families with hereditary angioedema: functional and structural correlates. Mol Immunol. 2008 Aug;45(13):3536-44. doi: 10.1016/j.molimm.2008.05.007. Epub 2008 Jun 30. Citation on PubMed
  • Sinnathamby ES, Issa PP, Roberts L, Norwood H, Malone K, Vemulapalli H, Ahmadzadeh S, Cornett EM, Shekoohi S, Kaye AD. Hereditary Angioedema: Diagnosis, Clinical Implications, and Pathophysiology. Adv Ther. 2023 Mar;40(3):814-827. doi: 10.1007/s12325-022-02401-0. Epub 2023 Jan 7. Citation on PubMed
  • Veronez CL, Csuka D, Sheikh FR, Zuraw BL, Farkas H, Bork K. The Expanding Spectrum of Mutations in Hereditary Angioedema. J Allergy Clin Immunol Pract. 2021 Jun;9(6):2229-2234. doi: 10.1016/j.jaip.2021.03.008. Epub 2021 Mar 19. Citation on PubMed
  • Wouters D, Wagenaar-Bos I, van Ham M, Zeerleder S. C1 inhibitor: just a serine protease inhibitor? New and old considerations on therapeutic applications of C1 inhibitor. Expert Opin Biol Ther. 2008 Aug;8(8):1225-40. doi: 10.1517/14712598.8.8.1225. Citation on PubMed
  • Zuraw BL. Clinical practice. Hereditary angioedema. N Engl J Med. 2008 Sep 4;359(10):1027-36. doi: 10.1056/NEJMcp0803977. No abstract available. Citation on PubMed

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