ABCMdb

ABCD4 p.Ala304Thr

Predicted by SNAP2:	C: D (91%), D: D (91%), E: D (91%), F: D (95%), G: D (80%), H: D (95%), I: D (91%), K: D (95%), L: D (95%), M: D (95%), N: D (91%), P: D (95%), Q: D (91%), R: D (95%), S: D (71%), T: D (75%), V: D (91%), W: D (95%), Y: D (95%),
Predicted by PROVEAN:	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, T: N, V: N, W: D, Y: D,

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Publications
[hide] Identification of novel SNPs of ABCD1, ABCD2, ABCD... Neurogenetics. 2011 Feb;12(1):41-50. Epub 2010 Jul 27. Matsukawa T, Asheuer M, Takahashi Y, Goto J, Suzuki Y, Shimozawa N, Takano H, Onodera O, Nishizawa M, Aubourg P, Tsuji S
Identification of novel SNPs of ABCD1, ABCD2, ABCD3, and ABCD4 genes in patients with X-linked adrenoleukodystrophy (ALD) based on comprehensive resequencing and association studies with ALD phenotypes.
Neurogenetics. 2011 Feb;12(1):41-50. Epub 2010 Jul 27., [PMID:20661612]

Abstract [show]
Adrenoleukodystrophy (ALD) is an X-linked disorder affecting primarily the white matter of the central nervous system occasionally accompanied by adrenal insufficiency. Despite the discovery of the causative gene, ABCD1, no clear genotype-phenotype correlations have been established. Association studies based on single nucleotide polymorphisms (SNPs) identified by comprehensive resequencing of genes related to ABCD1 may reveal genes modifying ALD phenotypes. We analyzed 40 Japanese patients with ALD. ABCD1 and ABCD2 were analyzed using a newly developed microarray-based resequencing system. ABCD3 and ABCD4 were analyzed by direct nucleotide sequence analysis. Replication studies were conducted on an independent French ALD cohort with extreme phenotypes. All the mutations of ABCD1 were identified, and there was no correlation between the genotypes and phenotypes of ALD. SNPs identified by the comprehensive resequencing of ABCD2, ABCD3, and ABCD4 were used for association studies. There were no significant associations between these SNPs and ALD phenotypes, except for the five SNPs of ABCD4, which are in complete disequilibrium in the Japanese population. These five SNPs were significantly less frequently represented in patients with adrenomyeloneuropathy (AMN) than in controls in the Japanese population (p=0.0468), whereas there were no significant differences in patients with childhood cerebral ALD (CCALD). The replication study employing these five SNPs on an independent French ALD cohort, however, showed no significant associations with CCALD or pure AMN. This study showed that ABCD2, ABCD3, and ABCD4 are less likely the disease-modifying genes, necessitating further studies to identify genes modifying ALD phenotypes.

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No. Sentence Comment
101 Gene Fragment SNP ID Category Amino acid change ABCD3 Exon1 rs4148058 5' untranslated region Exon2 rs2147794 Intron Exon3 rs16946 Coding synonymous Exon7 rs681187 Intron Exon23 rs662813 3' untranslated region Exon23 rs337592 3' untranslated region ABCD4 5'UTR rs17782508a Upstream at the transcription start site Intron1 rs17182959 Intron Intron1 rs17158118 Intron Exon3 rs2301345a Coding synonymous L62L Exon9 rs4148077a Coding nonsynonymous A304T Exon10 rs4148078a Coding synonymous L320L Exon11 rs3742801a Coding nonsynonymous E368K Table 4 Summary of identified single nucleotide polymorphism (SNPs) of ABCD2, ABCD3, and ABCD4 in 40 adrenoleukodystrophy patients: known SNPs A total of 24 SNPs of ABCD2, ABCD3, and ABCD4 were identified in 40 ALD patients. Among them, 11 SNPs (45.8%) were novel SNPs. Login to comment
108 Among the SNPs with suggestive association in the Japanese patients (rs17782508, rs2301345, rs4148077, rs4148078, and rs3742801), rs4148077 (A304T) substitutes a hydrophilic amino acid for a hydrophobic amino acid, and rs3742801 (E368K) substitutes a basic amino acid for an acidic amino acid. Login to comment