ABCG8 p.Arg412*
| ClinVar: |
c.1234C>T
,
p.Arg412*
D
, Pathogenic
|
[switch to compact view]
Comments [show]
None has been submitted yet.
[hide] Mutations in the human ATP-binding cassette transp... Hum Mutat. 2002 Aug;20(2):151. Heimerl S, Langmann T, Moehle C, Mauerer R, Dean M, Beil FU, von Bergmann K, Schmitz G
Mutations in the human ATP-binding cassette transporters ABCG5 and ABCG8 in sitosterolemia.
Hum Mutat. 2002 Aug;20(2):151., [PMID:12124998]
Abstract [show]
Phytosterolemia or Sitosterolemia is a rare autosomal recessive disorder characterized by highly elevated plasma levels of plant sterols and cholesterol as a consequence of hyperabsorption and impaired biliary secretion of sterols. The disease is caused by mutations in two half size ATP-binding cassette transporters, ABCG5 and ABCG8. We have analyzed the genomic sequence of ABCG5 and ABCG8 in five well-characterized patients with Sitosterolemia. In the first patient we found a heterozygous mutation in exon 8 of the ABCG5 gene leading to a premature termination of the protein (Arg408Ter). This German patient is the first European showing a mutation of the ABCG5 gene. In a second patient we found a novel heterozygous mutation in exon 5 of ABCG8 (c.584T>A; Leu195Gln). Both patients were heterozygous for the identified mutation, but no mutation could be identified on the other chromosome. In three further analyzed patients we found mutations in exons 7, 9 and 11 of the ABCG8 gene, respectively, of which two result in a premature termination signal for translation products. One of these patients was compound heterozygous (Trp361Ter and Arg412Ter), the other was homozygous for Trp361Ter. The third patient was homozygous for an amino acid exchange (Gly574Arg). In conclusion this report describes one novel mutation affecting a highly conserved amino acid and two previously identified mutations in the ABCG8 gene. In addition, we identified for the first time a mutation in the ABCG5 gene of a European Sitosterolemia patient.
Comments [show]
None has been submitted yet.
No. Sentence Comment
77 C Y658stop R121stop R164stop Q172stop R184H L195Q P231T G574R G574E L572P L596R N ABC B S AA R263Q E146Q R405H R543S W536stop R412stop W361stop C R419P R419H R408stop R398H N437K R550S R243stop N ABCG5 ABCG8 S B A IVS1 -2A>G Del547C>191stop L501P L596R 1568_1572delTCTTT 1798_1800delTTC Del Exon 3 C336-337insA 201 * Signature 250 ABCG1 Q..EKDEG.R REMVKEILTA L GLLSCANTR TGS.... .LS GGQR KRLAIA ABCG2 ATTMTNHE.K NERINRVIEE L GLDKVADSK VGTQFIR GVS GGER KRTSIG ABCG4 S..EKQEV.K KELVTEILTA L GLMSCSHTR TAL.... .LS GGQR KRLAIA ABCG5 R..RGNPGSF QKKVEAVMAE L SLSHVADRL IGNYSLG GIS TGER RRVSIA ABCG8 PRTFSQAQ.R DKRVEDVIAE L RLRQCADTR VGNMYVR GLS GGER RRVSIG Figure 2: Alignment of the human ABC transporters G1, G2, G4, G5 and G8. The amino acid change Leu195Gln in ABCG8 found in patient 2 is located intracellularly between the Walker A and the Signature C-motif.
X
ABCG8 p.Arg412* 12124998:77:126
status: VERIFIED[hide] Genetic disorders associated with ATP binding cass... Mol Genet Metab. 2002 Sep-Oct;77(1-2):13-20. Burris TP, Eacho PI, Cao G
Genetic disorders associated with ATP binding cassette cholesterol transporters.
Mol Genet Metab. 2002 Sep-Oct;77(1-2):13-20., [PMID:12359125]
Abstract [show]
Coronary artery disease is the most prevalent form of mortality and morbidity in Western countries. Studies in the last several decades have identified high LDL cholesterol and low HDL cholesterol as major risk factors leading to the disease. Human genetic studies have provided significant insight into the regulation of lipoprotein metabolism. In the last several years, the genes associated with several rare genetic diseases of lipid metabolism have been revealed. These landmark discoveries that identified mutant ABC cholesterol transporters as the underlying causes of these genetic disorders have paved the way for better understanding of the cellular cholesterol transport process and HDL biogenesis. This summary provides an overview and discussion of the most recent progress that includes molecular mechanism and regulation of cholesterol transport mediated by these ABC transporters.
Comments [show]
None has been submitted yet.
No. Sentence Comment
112 Regulation of ABC cholesterol transporters by LXR/ RXR heterodimer One feature of ABC transporters is that they are usually feed back/forward regulated by their own sub-Table 2 Summary of mutations described in sitosterolemia Nucleotide sequence change Protein sequence change ABC transporters References 402Del Truncated protein ABCG5 [12] C867T R243X ABCG5 [12] G1306A R389H ABCG5 [12] C1362T R408X ABCG5 [11,12] G1396A R419H ABCG5 [12] G1396C R419P ABCG5 [12] 547Del P231T ABCG8 [11] A691C 191Stop ABCG8 [11] G788A R263Q ABCG8 [11] G1083A W361Stop ABCG8 [11] C1234T R412stop ABCG8 [11] G1720A G574R ABCG8 [11] T1787G L596R ABCG8 [11] C1974G Y658Stop ABCG8 [11] strates at the level of transcription.
X
ABCG8 p.Arg412* 12359125:112:569
status: NEW