Defective SLC4A4 does not cotransport Na+ with 3HCO3-

Stable Identifier
R-HSA-5656219
Type
Reaction [transition]
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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. Mutations causing pRTA-OA include Q29*, R298S, S427L, T485S, R510H, W516*, A799V and a 65bp-del (Igarashi et al. 1999, Dinour et al. 2004, Horita et al. 2005, Lo et al. 2011, Suzuki et al. 2010).

Literature References
PubMed ID Title Journal Year
15471865 A novel missense mutation in the sodium bicarbonate cotransporter (NBCe1/SLC4A4) causes proximal tubular acidosis and glaucoma through ion transport defects

Dinour, D, Chang, MH, Satoh, J, Smith, BL, Angle, N, Knecht, A, Serban, I, Holtzman, EJ, Romero, MF

J. Biol. Chem. 2004
21228764 Severe metabolic acidosis causes early lethality in NBC1 W516X knock-in mice as a model of human isolated proximal renal tubular acidosis

Lo, YF, Yang, SS, Seki, G, Yamada, H, Horita, S, Yamazaki, O, Fujita, T, Usui, T, Tsai, JD, Yu, IS, Lin, SW, Lin, SH

Kidney Int. 2011
10545938 Mutations in SLC4A4 cause permanent isolated proximal renal tubular acidosis with ocular abnormalities

Igarashi, T, Inatomi, J, Sekine, T, Cha, SH, Kanai, Y, Kunimi, M, Tsukamoto, K, Satoh, H, Shimadzu, M, Tozawa, F, Mori, T, Shiobara, M, Seki, G, Endou, H

Nat Genet 1999
20798035 Defective membrane expression of the Na(+)-HCO(3)(-) cotransporter NBCe1 is associated with familial migraine

Suzuki, M, Van Paesschen, W, Stalmans, I, Horita, S, Yamada, H, Bergmans, BA, Legius, E, Riant, F, De Jonghe, P, Li, Y, Sekine, T, Igarashi, T, Fujimoto, I, Mikoshiba, K, Shimadzu, M, Shiohara, M, Braverman, N, Al-Gazali, L, Fujita, T, Seki, G

Proc. Natl. Acad. Sci. U.S.A. 2010
15930088 Functional analysis of NBC1 mutants associated with proximal renal tubular acidosis and ocular abnormalities

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

J. Am. Soc. Nephrol. 2005
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
sodium:bicarbonate symporter activity of SLC4A4 mutants [plasma membrane]
Physical Entity
Activity
Normal reaction
Disease
Name Identifier Synonyms
renal tubular acidosis 14219
Authored
Reviewed
Created
Cite Us!