Functional impact of titin (TTN) mutations in ocular surface squamous neoplasia

Mak B. Djulbegovic, Vladimir N. Uversky, Carol L. Karp, J. William Harbour

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Mutations in the titin (TTN) gene are among the most common genomic aberrations in ocular surface squamous neoplasia (OSSN), the most common cancer of the external eye. Further, TTN mutations are associated with resistance to standard therapy with topical interferon alpha-2b (IFN-α2b). However, it remains unclear how TTN mutations drive OSSN pathogenesis and treatment resistance. TTN encodes the largest protein in the human body and its best understood function is as a myofibril scaffold in striated muscle. However, recent evidence indicates that TTN has additional functions in non-muscle cells and in cancer. Here, we performed a disorder-based bioinformatics analysis which revealed that intrinsically disordered protein regions are abundant in TTN and provide mechanistic insights into its function as a nuclear protein in epithelial cells. Specific mutations found in OSSN are predicted to affect its intrinsically disordered protein regions (IDPRs), promoting chromosomal instability, oncogenesis, and altered response to IFN-α2b treatment.

Original languageEnglish (US)
Pages (from-to)93-101
Number of pages9
JournalInternational Journal of Biological Macromolecules
StatePublished - Jan 15 2022
Externally publishedYes


  • Interferon alpha-2b
  • Intrinsic disorder
  • Ocular surface squamous neoplasia
  • Titin

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Economics and Econometrics
  • Energy(all)


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