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MKKS gene

Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

MKKS Gene

The MKKS gene encodes a chaperonin‑like protein essential for early limb, heart, and reproductive development and for ciliary function; pathogenic variants cause McKusick‑Kaufman syndrome and Bardet‑Biedl syndrome.

Overview

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. This condition affects the development of the hands, feet, heart, and reproductive system. Two particular variants have been found to cause the syndrome in the Old Order Amish population. Each of these variants changes a single protein building block (amino acid) in the MKKS protein:

  • p.His84Tyr (p.H84Y) – histidine is replaced by tyrosine at position 84.
  • p.Ala242Ser (p.A242S) – alanine is replaced by serine at position 242.

Individuals with McKusick‑Kaufman syndrome in this population typically have both variants in each copy of the MKKS gene. This combination is rarely found in affected individuals outside the Old Order Amish.

Some variants in the MKKS gene can also cause Bardet‑Biedl syndrome, a related condition.

Although the exact mechanism is unclear, the p.His84Tyr and p.Ala242Ser variants may impair the protein's ability to deliver SMARCC1 into the nucleus, affecting the activity of genes critical during early development.

Bardet‑Biedl syndrome

MedlinePlus Genetics provides information about Bardet‑Biedl syndrome.

Other Names for This Gene

  • BBS6
  • HMCS
  • KMS
  • MKS

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

  • Tests of MKKS

Scientific Articles on PubMed

  • PubMed

Catalog of Genes and Diseases from OMIM

  • MKKS CENTROSOMAL SHUTTLING PROTEIN; MKKS

Gene and Variant Databases

  • NCBI Gene
  • ClinVar

Genomic Location

The MKKS gene is found on chromosome 20.

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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Slavotinek AM. McKusick‑Kaufman Syndrome. 2002 Sep 10 [updated 2020 Dec 3]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993‑2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK1502/.
  • 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.

Frequently Asked Questions

The hallmark features include postaxial polydactyly, which is the presence of extra fingers or toes on the outer side of the hand or foot. This is frequently accompanied by congenital heart defects, such as atrial or ventricular septal defects, and genital abnormalities. In males, these reproductive issues often manifest as hypospadias or undescended testes, while in females, they may involve structural anomalies of the uterus or ovaries. The combination of these specific limb and organ findings is what clinically differentiates it from other ciliopathies.
The condition follows an autosomal recessive inheritance pattern, meaning an individual must inherit two mutated copies of the MKKS gene, one from each parent, to develop the syndrome. Parents who are carriers typically do not show any symptoms. If a couple has one child with McKusick-Kaufman syndrome, there is a 25 percent chance with each subsequent pregnancy that the child will also be affected, a 50 percent chance the child will be an unaffected carrier, and a 25 percent chance the child will be neither affected nor a carrier. Genetic counseling is recommended to discuss these risks and potential testing options.
Yes, ongoing surveillance is critical because the syndrome affects multiple organ systems. Patients require regular cardiology evaluations to monitor for heart defects and potential arrhythmias. Additionally, urological and gynecological follow-ups are necessary to manage reproductive health issues, such as infertility or structural abnormalities. Because the MKKS gene is also linked to Bardet-Biedl syndrome, clinicians may also monitor for ciliopathy-related complications like retinal dystrophy or renal anomalies, although these are more characteristic of BBS. Early intervention and consistent monitoring can significantly improve quality of life and manage associated health risks.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.