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

MKKS gene

MKKS centrosomal shuttling protein

Normal Function

The MKKS gene (also called the BBS6 gene) provides instructions for making a protein that plays an important role in early development, specifically in the formation of the limbs, heart, and reproductive system. This protein's structure suggests that it may belong to a family of proteins called chaperonins. Proteins must be folded into the correct shape to function properly, and chaperonins help them do that.

The MKKS protein combines with other proteins to form a structure known as the chaperonin complex. The chaperonin complex serves as a scaffold for the assembly of another molecule called the BBSome. The BBSome helps transport materials that support the function of cilia, the microscopic, finger-like projections on the surface of cells. Cilia help transmit information.

Researchers speculate that the MKKS protein may also be directly involved in transporting important molecules to different locations within the cell. Specifically, the MKKS protein may help transport SMARCC1 protein from the cytoplasm into the nucleus of the cell. SMARCC1 helps regulate the activity of certain genes.

Health Conditions Related to Genetic Changes

McKusick-Kaufman syndrome

A few variants (also called mutations) in the MKKS gene have been found to cause McKusick-Kaufman syndrome. McKusick-Kaufman syndrome is a condition that affects the development of the hands, feet, heart, and reproductive system. Two particular variants have been found to cause McKusick-Kaufman syndrome in the Old Order Amish population.  Each of these variants changes a single protein building block (amino acid) in the MKKS protein. One variant replaces the amino acid histidine with the amino acid tyrosine at protein position 84 (written as p.His84Tyr or p.H84Y). The other variant replaces the amino acid alanine with the amino acid serine at protein position 242 (written as p.Ala242Ser or p.A242S). Those with McKusick-Kaufman syndrome in the Old Order Amish population typically have both of these variants in each copy of the MKKS gene. This combination of variants is rarely found in individuals with McKusick-Kaufman syndrome outside of the Old Order Amish population. 

Some variants in the MKKS gene can also cause Bardet-Biedl syndrome, a condition that is related to McKusick-Kaufman syndrome.

Though it is not clear exactly how variants in the MKKS gene lead to the specific signs and symptoms of McKusick-Kaufman syndrome, the p.His84Tyr and p.Ala242Ser variants may impair the protein's ability to deliver SMARCC1 into the nucleus of the cell. This change likely affects the activity of certain genes that are critical during early development.


More About This Health Condition

Bardet-Biedl syndrome

MedlinePlus Genetics provides information about Bardet-Biedl syndrome

More About This Health Condition

Other Names for This Gene

  • BBS6
  • HMCS
  • KMS
  • MKS

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

  • Hirayama S, Yamazaki Y, Kitamura A, Oda Y, Morito D, Okawa K, Kimura H, Cyr DM, Kubota H, Nagata K. MKKS is a centrosome-shuttling protein degraded by disease-causing mutations via CHIP-mediated ubiquitination. Mol Biol Cell. 2008 Mar;19(3):899-911. doi: 10.1091/mbc.e07-07-0631. Epub 2007 Dec 19. Citation on PubMed or Free article on PubMed Central
  • Katsanis N, Beales PL, Woods MO, Lewis RA, Green JS, Parfrey PS, Ansley SJ, Davidson WS, Lupski JR. Mutations in MKKS cause obesity, retinal dystrophy and renal malformations associated with Bardet-Biedl syndrome. Nat Genet. 2000 Sep;26(1):67-70. doi: 10.1038/79201. Citation on PubMed
  • Kim JC, Ou YY, Badano JL, Esmail MA, Leitch CC, Fiedrich E, Beales PL, Archibald JM, Katsanis N, Rattner JB, Leroux MR. MKKS/BBS6, a divergent chaperonin-like protein linked to the obesity disorder Bardet-Biedl syndrome, is a novel centrosomal component required for cytokinesis. J Cell Sci. 2005 Mar 1;118(Pt 5):1007-20. doi: 10.1242/jcs.01676. Citation on PubMed
  • Scott CA, Marsden AN, Rebagliati MR, Zhang Q, Chamling X, Searby CC, Baye LM, Sheffield VC, Slusarski DC. Nuclear/cytoplasmic transport defects in BBS6 underlie congenital heart disease through perturbation of a chromatin remodeling protein. PLoS Genet. 2017 Jul 28;13(7):e1006936. doi: 10.1371/journal.pgen.1006936. eCollection 2017 Jul. Citation on PubMed
  • Seo S, Baye LM, Schulz NP, Beck JS, Zhang Q, Slusarski DC, Sheffield VC. BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family chaperonins and mediate BBSome assembly. Proc Natl Acad Sci U S A. 2010 Jan 26;107(4):1488-93. doi: 10.1073/pnas.0910268107. Epub 2010 Jan 4. Citation on PubMed or Free article on PubMed Central
  • Slavotinek AM, Biesecker LG. Unfolding the role of chaperones and chaperonins in human disease. Trends Genet. 2001 Sep;17(9):528-35. doi: 10.1016/s0168-9525(01)02413-1. Citation on PubMed
  • Slavotinek AM, Searby C, Al-Gazali L, Hennekam RC, Schrander-Stumpel C, Orcana-Losa M, Pardo-Reoyo S, Cantani A, Kumar D, Capellini Q, Neri G, Zackai E, Biesecker LG. Mutation analysis of the MKKS gene in McKusick-Kaufman syndrome and selected Bardet-Biedl syndrome patients. Hum Genet. 2002 Jun;110(6):561-7. doi: 10.1007/s00439-002-0733-3. Epub 2002 May 9. Citation on PubMed
  • Slavotinek AM, Stone EM, Mykytyn K, Heckenlively JR, Green JS, Heon E, Musarella MA, Parfrey PS, Sheffield VC, Biesecker LG. Mutations in MKKS cause Bardet-Biedl syndrome. Nat Genet. 2000 Sep;26(1):15-6. doi: 10.1038/79116. Erratum In: Nat Genet 2001 Jun;28(2):193. Citation on PubMed
  • Slavotinek AM. McKusick-Kaufman Syndrome. 2002 Sep 10 [updated 2020 Dec 3]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from http://www.ncbi.nlm.nih.gov/books/NBK1502/ Citation on PubMed
  • Stone DL, Slavotinek A, Bouffard GG, Banerjee-Basu S, Baxevanis AD, Barr M, Biesecker LG. Mutation of a gene encoding a putative chaperonin causes McKusick-Kaufman syndrome. Nat Genet. 2000 May;25(1):79-82. doi: 10.1038/75637. Citation on PubMed

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