Targeting and intracellular trafficking of clinically relevant hTHTR1 mutations in human cell lines

Veedamali S. Subramanian, Jonathan S. Marchant, Hamid M. Said

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


The micronutrient thiamine is required for normal growth and development of human tissues, and is accumulated into cells through the activity of plasma membrane thiamine transporters, e.g. hTHTR1 (human thiamine transporter 1). Recent genetic evidence has linked mutations in hTHTR1 with the manifestation of TRMA (thiamine-responsive megaloblastic anaemia), a condition also associated with diabetes mellitus, sensorineural deafness and retinal disorders. To examine how mutations in hTHTR1 impair thiamine accumulation, we have investigated the targeting and functional properties of several different hTHTR1 mutants in human cell lines derived from epithelia relevant to thiamine absorption or tissues implicated in TRMA pathology. These constructs encompassed two newly identified point mutations (P51L and T158R) and two truncations of hTHTR1 identical with those found in TRMA kindreds (W358X and Δ383fs). Our results reveal a spectrum of mutant phenotypes, underlining that TRMA can result from decreased thiamine transport activity underpinned by changes in hTHTR1 expression levels, cellular targeting and/or protein transport activity.

Original languageEnglish (US)
Pages (from-to)93-102
Number of pages10
JournalClinical science
Issue number1-2
StatePublished - Jul 2007


  • Cellular targeting
  • Human thiamine transporter (hTHTR)
  • Micronutrient
  • Thiamine
  • Thiamine-responsive megaloblastic anaemia (TRMA)
  • Transporter
  • Vitamin


Dive into the research topics of 'Targeting and intracellular trafficking of clinically relevant hTHTR1 mutations in human cell lines'. Together they form a unique fingerprint.

Cite this