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TMEM237 is mutated in individuals with a Joubert syndrome related disorder and expands the role of the TMEM family at the ciliary transition zone.

Publication ,  Journal Article
Huang, L; Szymanska, K; Jensen, VL; Janecke, AR; Innes, AM; Davis, EE; Frosk, P; Li, C; Willer, JR; Chodirker, BN; Greenberg, CR; McLeod, DR ...
Published in: Am J Hum Genet
December 9, 2011

Joubert syndrome related disorders (JSRDs) have broad but variable phenotypic overlap with other ciliopathies. The molecular etiology of this overlap is unclear but probably arises from disrupting common functional module components within primary cilia. To identify additional module elements associated with JSRDs, we performed homozygosity mapping followed by next-generation sequencing (NGS) and uncovered mutations in TMEM237 (previously known as ALS2CR4). We show that loss of the mammalian TMEM237, which localizes to the ciliary transition zone (TZ), results in defective ciliogenesis and deregulation of Wnt signaling. Furthermore, disruption of Danio rerio (zebrafish) tmem237 expression produces gastrulation defects consistent with ciliary dysfunction, and Caenorhabditis elegans jbts-14 genetically interacts with nphp-4, encoding another TZ protein, to control basal body-TZ anchoring to the membrane and ciliogenesis. Both mammalian and C. elegans TMEM237/JBTS-14 require RPGRIP1L/MKS5 for proper TZ localization, and we demonstrate additional functional interactions between C. elegans JBTS-14 and MKS-2/TMEM216, MKSR-1/B9D1, and MKSR-2/B9D2. Collectively, our findings integrate TMEM237/JBTS-14 in a complex interaction network of TZ-associated proteins and reveal a growing contribution of a TZ functional module to the spectrum of ciliopathy phenotypes.

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Published In

Am J Hum Genet

DOI

EISSN

1537-6605

Publication Date

December 9, 2011

Volume

89

Issue

6

Start / End Page

713 / 730

Location

United States

Related Subject Headings

  • Zebrafish
  • Wnt Signaling Pathway
  • Wnt Proteins
  • Sequence Analysis, DNA
  • Retina
  • Polymorphism, Single Nucleotide
  • Mutation
  • Multiprotein Complexes
  • Microscopy, Electron, Transmission
  • Mice
 

Citation

APA
Chicago
ICMJE
MLA
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Huang, L., Szymanska, K., Jensen, V. L., Janecke, A. R., Innes, A. M., Davis, E. E., … Boycott, K. M. (2011). TMEM237 is mutated in individuals with a Joubert syndrome related disorder and expands the role of the TMEM family at the ciliary transition zone. Am J Hum Genet, 89(6), 713–730. https://doi.org/10.1016/j.ajhg.2011.11.005
Huang, Lijia, Katarzyna Szymanska, Victor L. Jensen, Andreas R. Janecke, A Micheil Innes, Erica E. Davis, Patrick Frosk, et al. “TMEM237 is mutated in individuals with a Joubert syndrome related disorder and expands the role of the TMEM family at the ciliary transition zone.Am J Hum Genet 89, no. 6 (December 9, 2011): 713–30. https://doi.org/10.1016/j.ajhg.2011.11.005.
Huang L, Szymanska K, Jensen VL, Janecke AR, Innes AM, Davis EE, et al. TMEM237 is mutated in individuals with a Joubert syndrome related disorder and expands the role of the TMEM family at the ciliary transition zone. Am J Hum Genet. 2011 Dec 9;89(6):713–30.
Huang, Lijia, et al. “TMEM237 is mutated in individuals with a Joubert syndrome related disorder and expands the role of the TMEM family at the ciliary transition zone.Am J Hum Genet, vol. 89, no. 6, Dec. 2011, pp. 713–30. Pubmed, doi:10.1016/j.ajhg.2011.11.005.
Huang L, Szymanska K, Jensen VL, Janecke AR, Innes AM, Davis EE, Frosk P, Li C, Willer JR, Chodirker BN, Greenberg CR, McLeod DR, Bernier FP, Chudley AE, Müller T, Shboul M, Logan CV, Loucks CM, Beaulieu CL, Bowie RV, Bell SM, Adkins J, Zuniga FI, Ross KD, Wang J, Ban MR, Becker C, Nürnberg P, Douglas S, Craft CM, Akimenko M-A, Hegele RA, Ober C, Utermann G, Bolz HJ, Bulman DE, Katsanis N, Blacque OE, Doherty D, Parboosingh JS, Leroux MR, Johnson CA, Boycott KM. TMEM237 is mutated in individuals with a Joubert syndrome related disorder and expands the role of the TMEM family at the ciliary transition zone. Am J Hum Genet. 2011 Dec 9;89(6):713–730.
Journal cover image

Published In

Am J Hum Genet

DOI

EISSN

1537-6605

Publication Date

December 9, 2011

Volume

89

Issue

6

Start / End Page

713 / 730

Location

United States

Related Subject Headings

  • Zebrafish
  • Wnt Signaling Pathway
  • Wnt Proteins
  • Sequence Analysis, DNA
  • Retina
  • Polymorphism, Single Nucleotide
  • Mutation
  • Multiprotein Complexes
  • Microscopy, Electron, Transmission
  • Mice