ABCD1 p.Thr693Met
| Predicted by SNAP2: | A: D (59%), C: D (75%), D: D (63%), E: D (63%), F: D (75%), G: D (63%), H: D (59%), I: D (71%), K: N (57%), L: D (75%), M: D (71%), N: N (72%), P: D (63%), Q: N (57%), R: D (59%), S: N (66%), V: D (66%), W: D (85%), Y: D (85%), |
| Predicted by PROVEAN: | A: N, C: N, D: N, E: N, F: N, G: N, H: N, I: N, K: N, L: N, M: N, N: N, P: N, Q: N, R: N, S: N, V: N, W: N, Y: N, |
[switch to compact view]
Comments [show]
None has been submitted yet.
[hide] ABCD1 mutations and the X-linked adrenoleukodystro... Hum Mutat. 2001 Dec;18(6):499-515. Kemp S, Pujol A, Waterham HR, van Geel BM, Boehm CD, Raymond GV, Cutting GR, Wanders RJ, Moser HW
ABCD1 mutations and the X-linked adrenoleukodystrophy mutation database: role in diagnosis and clinical correlations.
Hum Mutat. 2001 Dec;18(6):499-515., [PMID:11748843]
Abstract [show]
X-linked adrenoleukodystrophy (X-ALD) is caused by mutations in the ABCD1 gene, which encodes a peroxisomal ABC half-transporter (ALDP) involved in the import of very long-chain fatty acids (VLCFA) into the peroxisome. The disease is characterized by a striking and unpredictable variation in phenotypic expression. Phenotypes include the rapidly progressive childhood cerebral form (CCALD), the milder adult form, adrenomyeloneuropathy (AMN), and variants without neurologic involvement. There is no apparent correlation between genotype and phenotype. In males, unambiguous diagnosis can be achieved by demonstration of elevated levels of VLCFA in plasma. In 15 to 20% of obligate heterozygotes, however, test results are false-negative. Therefore, mutation analysis is the only reliable method for the identification of heterozygotes. Since most X-ALD kindreds have a unique mutation, a great number of mutations have been identified in the ABCD1 gene in the last seven years. In order to catalog and facilitate the analysis of these mutations, we have established a mutation database for X-ALD ( http://www.x-ald.nl). In this review we report a detailed analysis of all 406 X-ALD mutations currently included in the database. Also, we present 47 novel mutations. In addition, we review the various X-ALD phenotypes, the different diagnostic tools, and the need for extended family screening for the identification of new patients.
Comments [show]
None has been submitted yet.
No. Sentence Comment
174 P560S 7 1678C>T n.d. # P560L 7 1679C>T Reduced P560L 7 1679C>T Reduced fs I588 7 1765delC n.d. # R591P 7 1772G>C Absent S606L 8 1817C>T Present E609K 8 1825G>A Absent E609K 8 1825G>A Absent R617C 8 1849C>T Absent R617H 8 1850G>A Absent R617H 8 1850G>A Absent A626T 9 1876G>A Absent A626T 9 1876G>A Absent A626D 9 1877C>A n.d. # E630G 9 1889A>G n.d. # C631Y 9 1892G>A n.d. # T632I 9 1895C>T n.d. # V635M 9 1903G>A n.d. # L654P 9 1961T>C Absent # R660W 9 1978C>T Absent fs L663 9 1988insT n.d. # fs L663 IVS 9 IVS9+1g>a n.d. # fs L663 IVS 9 IVS9-1g>a n.d. # H667D 10 1999C>G Absent # T668I 10 2003C>T Absent # T693M 10 2078C>T Present # exon1-5del 1-5 n.d. # The 47 mutations marked with a # are novel unique mutations reported for the first time in this paper.
X
ABCD1 p.Thr693Met 11748843:174:608
status: NEW[hide] Identification of a new fatty acid synthesis-trans... J Biol Chem. 2012 Jan 2;287(1):210-21. Epub 2011 Nov 1. Hillebrand M, Gersting SW, Lotz-Havla AS, Schafer A, Rosewich H, Valerius O, Muntau AC, Gartner J
Identification of a new fatty acid synthesis-transport machinery at the peroxisomal membrane.
J Biol Chem. 2012 Jan 2;287(1):210-21. Epub 2011 Nov 1., [PMID:22045812]
Abstract [show]
The neurodegenerative disease X-linked adrenoleukodystrophy (X-ALD) is characterized by the abnormal accumulation of very long chain fatty acids. Mutations in the gene encoding the peroxisomal ATP-binding cassette half-transporter, adrenoleukodystrophy protein (ALDP), are the primary cause of X-ALD. To gain a better understanding of ALDP dysfunction, we searched for interaction partners of ALDP and identified binary interactions to proteins with functions in fatty acid synthesis (ACLY, FASN, and ACC) and activation (FATP4), constituting a thus far unknown fatty acid synthesis-transport machinery at the cytoplasmic side of the peroxisomal membrane. This machinery adds to the knowledge of the complex mechanisms of peroxisomal fatty acid metabolism at a molecular level and elucidates potential epigenetic mechanisms as regulatory processes in the pathogenesis and thus the clinical course of X-ALD.
Comments [show]
None has been submitted yet.
No. Sentence Comment
231 We analyzed, whether five missense mutations in the ABCD1 gene known to be associated with near normal ALDP protein amounts (G116R, S514N, G607D, G629H, and T693M) would induce edgetic perturbations by altering ALDP homo-oligomerization or the interaction of ALDP with FASN, ACLY, or FATP4 (Fig. 5).
X
ABCD1 p.Thr693Met 22045812:231:157
status: NEW273 WT ALDP was compared with ALDP constructs representing disease-causing missense mutations (G116R, S514N, G607D, G629H, and T693M); homomeric interactions as well as interactions with FASN, ACLY, and FATP4 were determined.
X
ABCD1 p.Thr693Met 22045812:273:123
status: NEW227 We analyzed, whether five missense mutations in the ABCD1 gene known to be associated with near normal ALDP protein amounts (G116R, S514N, G607D, G629H, and T693M) would induce edgetic perturbations by altering ALDP homo-oligomerization or the interaction of ALDP with FASN, ACLY, or FATP4 (Fig. 5).
X
ABCD1 p.Thr693Met 22045812:227:157
status: NEW229 Conversely, S514N and G607D increased the BRET ratio for the interaction of ALDP with FASN, whereas G116R had the same effect on the interaction between ALDP and ACLY.
X
ABCD1 p.Thr693Met 22045812:229:157
status: NEW269 WT ALDP was compared with ALDP constructs representing disease-causing missense mutations (G116R, S514N, G607D, G629H, and T693M); homomeric interactions as well as interactions with FASN, ACLY, and FATP4 were determined.
X
ABCD1 p.Thr693Met 22045812:269:123
status: NEW271 WT ALDP was compared with ALDP constructs representing disease-causing missense mutations (G116R, S514N, G607D, G629H, and T693M); homomeric interactions as well as interactions with FASN, ACLY, and FATP4 were determined.
X
ABCD1 p.Thr693Met 22045812:271:123
status: NEW