TTLL5 gene


Gene (OMIM No.)
Function of gene/protein
  • Protein: tubulin tyrosine ligase-like family, member 5
  • Polyglutamylation of the primary cilia
  • Normal functioning of sperm flagella
  • Stabilising the microtubules of the photoreceptor cilia
Clinical phenotype
(OMIM phenotype no.)
  • Autosomal recessive
Ocular features
  • Consistent fundal phenotype best appreciated on fundus autofluorescence (FAF) imaging
  • Hyper-autofluorescent perifoveal ring surrounding an area of irregular foveal autofluorescence
  • Outer retinal and RPE degeneration mainly confined to the foveal region observed on OCT
  • Normal AF signal peripheral to the perifoveal ring
Visual function
  • Patients usually present during 30s to 40s with central visual disturbance but earlier onset disease (childhood) have been reported in minority
  • Progressive central vision deterioration and mild peripheral visual field constriction
Systemic features
  • Infertility due to significant reduction in sperm motility reported in two unrelated male patients harbouring two truncating TTLL5 variants
  • Not a consistent finding as other affected males with two truncating alleles have children
Key investigations
  • Electrophysiology
  • Fundus autofluorescence (FAF)
  • Optical coherence tomography (OCT)
  • Kinetic perimetry
Molecular diagnosisNext generation sequencing
  • Targeted gene panels (retinal)
  • Whole exome sequencing
  • Whole genome sequencing
Therapies under research
  • None at present
Further information

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  1.  Backer CB, Gutzman JH, Pearson CG, Cheeseman IM. CSAP localizes to polyglutamylated microtubules and promotes proper cilia function and zebrafish development. Mol Biol Cell. 2012;23(11):2122-2130
  2.  Lee GS, He Y, Dougherty EJ, et al. Disruption of Ttll5/stamp gene (tubulin tyrosine ligase-like protein 5/SRC-1 and TIF2-associated modulatory protein gene) in male mice causes sperm malformation and infertility. J Biol Chem. 2013;288(21):15167-15180
  3.  Sergouniotis PI, Chakarova C, Murphy C, et al. Biallelic variants in TTLL5, encoding a tubulin glutamylase, cause retinal dystrophy. Am J Hum Genet. 2014;94(5):760-769
  4.  Bedoni N, Haer-Wigman L, Vaclavik V, et al. Mutations in the polyglutamylase gene TTLL5, expressed in photoreceptor cells and spermatozoa, are associated with cone-rod degeneration and reduced male fertility. Hum Mol Genet. 2016;25(20):4546-4555

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Updated on January 24, 2021
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