Defective SLC4A4 causes renal tubular acidosis, proximal, with ocular abnormalities and mental retardation (pRTA-OA)

Stable Identifier
Homo sapiens
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this pathway in the Pathway Browser
Members 4, 5, 7 and 9 of the SLC4A family couple the transport of bicarbonate (HCO3-) with sodium ions (Na+). SLC4A4 (aka NBCe1) is an electrogenic Na+/HCO3- cotransporter with a stoichiometry of 1:3. SLC4A4 is expressed in the kidney and pancreas, with lesser expression in many other tissues. Mutations in SLC4A4 can cause permanent isolated proximal renal tubular acidosis with ocular abnormalities and mental retardation (pRTA-OA), a rare autosomal recessive syndrome characterised by short stature, proximal renal tubular acidosis, mental retardation, bilateral glaucoma, cataracts and bandkeratopathy. pRTA results from the failure of the proximal tubular cells to reabsorb filtered HCO3- from urine, leading to urinary HCO3- wasting and subsequent acidemia. HCO3- also needs to move out of cells in the eye, thus failure to do so can affect ocular pressure homeostasis (Horita et al. 2005, Kurtz & Zhu 2013, Kurtz & Zhu 2013b, Seki et al. 2013).
Literature References
PubMed ID Title Journal Year
24101904 Molecular mechanisms of renal and extrarenal manifestations caused by inactivation of the electrogenic Na(+)-HCO3 (-) cotransporter NBCe1

Horita, S, Yamazaki, O, Usui, T, Suzuki, M, Seki, G, Yamada, H, Nakamura, M

Front Physiol 2013
24391589 Proximal renal tubular acidosis mediated by mutations in NBCe1-A: unraveling the transporter's structure-functional properties

Zhu, Q, Kurtz, I

Front Physiol 2013
23917030 Structure, function, and regulation of the SLC4 NBCe1 transporter and its role in causing proximal renal tubular acidosis

Zhu, Q, Kurtz, I

Curr. Opin. Nephrol. Hypertens. 2013
15930088 Functional analysis of NBC1 mutants associated with proximal renal tubular acidosis and ocular abnormalities

Moriyama, N, Dasouki, M, Horita, S, Shimadzu, M, Fujita, T, Sekine, T, Al-Gazali, L, Endo, Y, Ekim, M, Inatomi, J, Seki, G, Igarashi, T, Yamada, H

J. Am. Soc. Nephrol. 2005
Name Identifier Synonyms
renal tubular acidosis DOID:14219
Cross References
BioModels Database
Cite Us!