Defective ABCD4:LMBRD1 does not transport Cbl from lysosomal lumen to cytosol

Stable Identifier
R-HSA-5683325
Type
Reaction [transition]
Species
Homo sapiens
Compartment
cytosol, lysosomal lumen, lysosomal membrane
ReviewStatus
5/5
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Defective ABCD4:LMBRD1 does not transport Cbl from lysosomal lumen to cytosol
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ATP-binding cassette sub-family D member 4 (ABCD4) is thought to mediate the lysosomal export of cobalamin (Cbl aka vitamin B12) into the cytosol, making it available for the production of Cbl cofactors. Cbl is an important cofactor for correct haematological and neurological functions. Defects in ABCD4 can cause methylmalonic aciduria and homocystinuria, cblJ type (MAHCJ; MIM:614857), a genetically heterogeneous metabolic disorder of Cbl metabolism characterised by decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl). Clinically, symptoms include feeding difficulties, poor growth, hypotonia, lethargy, anaemia and delayed development. Mutations causing MAHCJ include Y319C and E583Lfs*9 (Coelho et al. 2012).
Literature References
PubMed ID Title Journal Year
22922874 Mutations in ABCD4 cause a new inborn error of vitamin B12 metabolism

Pasquali, M, Rosenblatt, DS, Mengel, E, Frapolli, M, Burda, P, du Moulin, M, Miousse, IR, Shoubridge, EA, Watkins, D, Stucki, M, Fung, S, Fowler, B, Nürnberg, P, Thiele, H, Kim, JC, Coelho, D, Baumgartner, MR, Höhne, W, Suormala, T, Rutsch, F, Buers, I, Majewski, J, Longo, N, Robenek, H

Nat. Genet. 2012
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Catalyst Activity

ABC-type vitamin B12 transporter activity of ABCD4 mutant:LBRD1 complexes [lysosomal membrane]

Physical Entity
ABCD4 mutant:LBRD1 complexes [lysosomal membrane] (Homo sapiens)
Activity
ABC-type vitamin B12 transporter activity (GO:0015420)
Normal reaction
ABCD4:LMBRD1 transports RCbl from lysosomal lumen to cytosol (gut mucosal cells) (Homo sapiens)
Functional status

Loss of function of ABCD4 mutant:LBRD1 complexes [lysosomal membrane]

Normal Entity
Disease Entity
Status
Disease
Name Identifier Synonyms
methylmalonic acidemia DOID:14749 METHYLMALONICACIDURIA DUE TO METHYLMALONIC CoA MUTASE deficiency, METHYLMALONIC ACIDURIA, mut TYPE, METHYLMALONIC ACIDEMIA, cblB TYPE, methylmalonic aciduria mut type, METHYLMALONICACIDURIA, vitamin B12-RESPONSIVE, DUE TO DEFECT IN SYNTHESIS OF ADENOSYLCOBALAMIN--cbl B, methylmalonic aciduria cblB type, METHYLMALONIC ACIDURIA DUE TO METHYLMALONYL-CoA MUTASE DEFICIENCY, METHYLMALONIC ACIDURIA, VITAMIN B12-RESPONSIVE, DUE TO DEFECT IN SYNTHESIS OF ADENOSYLCOBALAMIN, cblA TYPE, methylmalonic aciduria, METHYLMALONIC ACIDURIA, VITAMIN B12-RESPONSIVE, DUE TO DEFECT IN SYNTHESIS OF ADENOSYLCOBALAMIN, cblB TYPE, METHYLMALONIC ACIDEMIA, cblA TYPE, METHYLMALONICACIDURIA, vitamin B12-RESPONSIVE, DUE TO DEFECT IN SYNTHESIS OF ADENOSYLCOBALAMIN--cbl A
homocystinuria DOID:9263 cystathionine beta synthase deficiency, cystathionine synthase deficiency, Homocystinuria (disorder), CBS deficiency
Authored
Jassal, B  (2015-03-13)
Reviewed
Shukla, S  (2015-09-15)
Created
Jassal, B  (2015-03-13)
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