Defective SRD5A3 does not reduce pPNOL to DCHOL

Stable Identifier
R-HSA-4755572
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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Polyprenol reductase (SRD5A3), resident on the endoplasmic reticulum membrane, normally mediates the reduction of the alpha-isoprene unit of polyprenol (pPNOL) to form dolichol (DCHOL) in a NADPH-dependent manner (Cantagrel et al. 2010). DCHOLs are substrates required for the synthesis of the lipid-linked oligosaccharide (LLO) precursor used for N-glycosylation. Defects in SRD5A3 cause congenital disorder of glycosylation 1q (SRD5A3-CDG, CDG1q; MIM:612379), a neurodevelopmental disorder characterised by under-glycosylated serum glycoproteins resulting in nervous system development, psychomotor retardation, hypotonia, coagulation disorders and immunodeficiency (Cantagrel et al. 2010, Kasapkara et al. 2012). Defects in SRD5A3 can also cause Kahrizi syndrome (KHRZ; MIM:612713), a neurodevelopmental disorder characterised by mental retardation, cataracts, holes in eye structures, pathological curvature of the spine, and coarse facial features (Kahrizi et al. 2011). Mutations that can cause SRD5A3-CDG are Q96*, Q107*, R142*, Y163* and S10* (Al-Gazali et al. 2008, Cantagrel et al. 2010). A mutation that can cause KHRZ is F69Lfs*2 (Kahrizi et al. 2009, Kahrizi et al. 2011).

Literature References
PubMed ID Title Journal Year
20700148 Next generation sequencing in a family with autosomal recessive Kahrizi syndrome (OMIM 612713) reveals a homozygous frameshift mutation in SRD5A3

Kahrizi, K, Hu, CH, Garshasbi, M, Abedini, SS, Ghadami, S, Kariminejad, R, Ullmann, R, Chen, W, Ropers, HH, Kuss, AW, Najmabadi, H, Tzschach, A

Eur. J. Hum. Genet. 2011
18781183 An autosomal recessive syndrome of severe mental retardation, cataract, coloboma and kyphosis maps to the pericentromeric region of chromosome 4

Kahrizi, K, Najmabadi, H, Kariminejad, R, Jamali, P, Malekpour, M, Garshasbi, M, Ropers, HH, Kuss, AW, Tzschach, A

Eur. J. Hum. Genet. 2009
20637498 SRD5A3 is required for converting polyprenol to dolichol and is mutated in a congenital glycosylation disorder

Cantagrel, V, Lefeber, DJ, Ng, BG, Guan, Z, Silhavy, JL, Bielas, SL, Lehle, L, Hombauer, H, Adamowicz, M, Swiezewska, E, De Brouwer, AP, Blümel, P, Sykut-Cegielska, J, Houliston, S, Swistun, D, Ali, BR, Dobyns, WB, Babovic-Vuksanovic, D, van Bokhoven, H, Wevers, RA, Raetz, CR, Freeze, HH, Morava, E, Al-Gazali, L, Gleeson, JG

Cell 2010
18271001 A new autosomal recessive syndrome of ocular colobomas, ichthyosis, brain malformations and endocrine abnormalities in an inbred Emirati family

Al-Gazali, L, Hertecant, J, Algawi, K, El Teraifi, H, Dattani, M

Am. J. Med. Genet. A 2008
22240719 SRD5A3-CDG: a patient with a novel mutation

Kasapkara, CS, Tümer, L, Ezgü, FS, Hasanoğlu, A, Race, V, Matthijs, G, Jaeken, J

Eur. J. Paediatr. Neurol. 2012
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor of SRD5A3 mutants [endoplasmic reticulum membrane]
Physical Entity
Activity
Normal reaction
Disease
Name Identifier Synonyms
congenital disorder of glycosylation type I 0050570
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