ABCMdb

ABCC8 p.Glu501Lys

None has been submitted yet.

Publications

PMID: 17575084 [PubMed] Yan FF et al: "Congenital hyperinsulinism associated ABCC8 mutations that cause defective trafficking of ATP-sensitive K+ channels: identification and rescue."

No. Sentence Comment

47 TABLE 1 Genetic and clinical information on patients carrying the CHI mutations Mutation Disease Haplotype Diazoxide response References G7R Focal G7R No 44 N24K Diffuse N24K/R1215W No Not reported F27S Focal F27S No 39 R74W Focal R74W/R1215Q No 39,45,46 E128K Diffuse E128K No Not reported R495Q Diffuse R495Q/R1215Q No 39 E501K Focal E501K No 39 L503P Focal L503P No 44 F686S Focal F686S No 39 G716V* Diffuse G716V/G716V No 47,48 K1337N Not done g3992-9a/K1337N Yes 39 L1350Q Focal L1350Q No 44 S1387F Diffuse S1387F/NA No 9,24 L1390P NA L1390P/NA No Not reported D1472H Diffuse ⌬F1388/D1472H No 39 *Patient was from consanguineous mating and therefore was homozygous for the G716V mutation (48). Login to comment
94 The first group, including G7R, N24K, F27S, R74W, and E128K, is located in the first transmembrane domain TMD0; the second group, including R495Q, E501K, L503P, F686S, and G716V, is located in the second transmembrane domain TMD1 extending through the first nucleotide binding domain; the third group, including K1337N, L1350Q, S1387F, L1390P, and D1472H, is clustered in the second nucleotide binding domain and the COOH terminus of the protein. Login to comment
118 Results from this assay showed that F27S, R74W, E128K, R495Q, E501K, L503P, F686S, G716V, L1350Q, and D1472H mutant channels had greatly reduced surface expression (Ͻ20% of wild-type level)-whereas G7R and N24K mutant channels displayed modestly decreased surface expression level (Ͼ30% but Ͻ50% of wild-type level) and K1337N, S1378F, and L1390P exhibited normal or mildly reduced expression (Ͼ60% of wild-type level; Fig. 3A). Login to comment
48 TABLE 1 Genetic and clinical information on patients carrying the CHI mutations Mutation Disease Haplotype Diazoxide response References G7R Focal G7R No 44 N24K Diffuse N24K/R1215W No Not reported F27S Focal F27S No 39 R74W Focal R74W/R1215Q No 39,45,46 E128K Diffuse E128K No Not reported R495Q Diffuse R495Q/R1215Q No 39 E501K Focal E501K No 39 L503P Focal L503P No 44 F686S Focal F686S No 39 G716V* Diffuse G716V/G716V No 47,48 K1337N Not done g3992-9a/K1337N Yes 39 L1350Q Focal L1350Q No 44 S1387F Diffuse S1387F/NA No 9,24 L1390P NA L1390P/NA No Not reported D1472H Diffuse èc;F1388/D1472H No 39 *Patient was from consanguineous mating and therefore was homozygous for the G716V mutation (48). Login to comment
95 The first group, including G7R, N24K, F27S, R74W, and E128K, is located in the first transmembrane domain TMD0; the second group, including R495Q, E501K, L503P, F686S, and G716V, is located in the second transmembrane domain TMD1 extending through the first nucleotide binding domain; the third group, including K1337N, L1350Q, S1387F, L1390P, and D1472H, is clustered in the second nucleotide binding domain and the COOH terminus of the protein. Login to comment
119 Results from this assay showed that F27S, R74W, E128K, R495Q, E501K, L503P, F686S, G716V, L1350Q, and D1472H mutant channels had greatly reduced surface expression (b0d;20% of wild-type level)-whereas G7R and N24K mutant channels displayed modestly decreased surface expression level (b0e;30% but b0d;50% of wild-type level) and K1337N, S1378F, and L1390P exhibited normal or mildly reduced expression (b0e;60% of wild-type level; Fig. 3A). Login to comment

PMID: 15562009 [PubMed] Henwood MJ et al: "Genotype-phenotype correlations in children with congenital hyperinsulinism due to recessive mutations of the adenosine triphosphate-sensitive potassium channel genes."

No. Sentence Comment

54 Gene Haplotype Calcium (␮U/ml) Leucine (␮U/ml) Glucose (␮U/ml) Tolbutamide (␮U/ml) Diazoxide responsive Diffuse HI 1 SUR1 delF1388/D1472H 6 2 13 -2 No 2 Kir6.2 G134A/P266L 20 3 36 -2 No 3 SUR1 g3992-9a/g1630ϩ1a 11 16 -2 No 4 SUR1 N188S/D1472N 7 1 7 7 No 5 SUR1 R598X/R999X 32 1 72 27 No 6 SUR1 R495Q/R1215Q -2 15 44 30 No 7 SUR1 R74W/R1215Q 52 28 20 98 No 8 SUR1 g3992-9a/K1337N 2 18 39 33 Yes Focal HI 9 SUR1 F27S 17 -1 16 29 No 10 SUR1 F686S 12 2 27 12 No 11 SUR1 E501K 6 3 9 10 No 12 SUR1 3576delg 9 6 9 12 No 13 SUR1 g3992-9a 5 8 25 9 No 14 SUR1 g3992-9a 3 8 40 21 No 15 SUR1 c2924-10a 4 8 67 29 No 16 Kir6.2 A101D 1 8 177 88 No 17 SUR1 R1215W 7 9 15 6 No 18 Kir6.2 R136L 8 10 115 21 No 19 SUR1 g3992-9a 40 15 35 -0.3 No 20 SUR1 6aa insertion in exon 5 6 16 22 15 No 21 SUR1 R1215W 38 47 58 15 No 22 Kir6.2 R301H 16 55 75 14 No Controls (␮U/ml, mean Ϯ SD) KATP HI (n ϭ 7) 28 Ϯ 16 5 Ϯ 8 12 Ϯ 9 4 Ϯ 6 No GDH-HI (n ϭ 7) 2.3 Ϯ 5.4 42 Ϯ 27 120 Ϯ 52 94 Ϯ 56 Yes Normal (n ϭ 6) 3 Ϯ 4 1.4 Ϯ 2.8 56 Ϯ 26 48 Ϯ 32 Yes a To convert insulin (␮U/ml to pmol/liter), multiply by 6.0. identified in other patients. Login to comment
107 Degree of residual channel function in KATP mutations Null Indeterminate Partial SUR1 g3992-9a g1630ϩ1a R598X/R999X delF1388 N188S/D1472N R495Q/R1215Q F27S 3576delg R74W/R1215Q F686S K1337N E501K 6 aa insertion in exon 5 c2924-10a R1215W Kir6.2 G134A/P266L R301H A101D R136L FIG. 1. Login to comment

PMID: 16357843 [PubMed] Suchi M et al: "Molecular and immunohistochemical analyses of the focal form of congenital hyperinsulinism."

No. Sentence Comment

93 KATP mutationsa Nuclear labeling of p57kip2 Microsatellite marker analysis at 11p15 Remarks on histology Lesion Islets in normal area 1 g3992-9a/ + ND 2 R1494Q/ + ND 3 V21D/ + ND 4 g3992-9a/ + ND 5 3576 del g/ Small lesion + ND 6 R74W/ Small normal area and weak Loss of maternal allele 7 C717X/ + Loss of maternal allele 8 1874 del c/ + ND 9 Q954X/ + ND 10 g3992-9g/ + Loss of maternal allele 11 E501K/ + Loss of maternal allele 12 R136Lb / Weak Loss of maternal allele 13 c2924-9a/ + Loss of maternal allele Focal lesion occupies large area of pancreas 14 g3992-9a/ + ND 15 3084 del g/ + ND 16 R302Hb / + Loss of maternal allele 17 g3992-9a/ + ND 18 536-539 del atgg/ + ND 19 R1215W/ + Loss of maternal allele 20 R999X/ + ND 21 L1350Q/ + ND 22 G1401R/ Weak Loss of maternal allele 23 g2041-21a/ + Loss of maternal allele 24 G7R/ Weak Loss of maternal allele 25 g3992-9a/ + Loss of maternal allele Rare nonadjacent large islet cell nuclei 26 g3992-9a/ + ND 27 Q954X/ + ND 28 delF1388/ + ND 29 Q472X/ + ND 30 G40Db / + Loss of maternal allele 31 S116Pb / + ND 32 g3992-9a/ + ND 33 g2116+1t, nonmaternal + ND 34 A101Db , nonmaternal Small normal area Loss of maternal allele Focal lesion occupies large area of pancreas 35 F27S, nonmaternal Weak Loss of maternal allele 36 G1379R, nonmaternal + ND 37 1631 del t, nonmaternal + ND 38 R1215W, nonmaternal + Loss of maternal allele 39 L503P, nonmaternal + Loss of maternal allele 40 F686S, de novo + Loss of maternal allele 41 1332+4 del c, maternalc + Loss of maternal allele 42 / + Loss of maternal allele 43 / + ND 44 / Small lesion + Loss of maternal allele 45 / + Loss of maternal allele 46 / + Loss of maternal allele 47 / + ND 48 / + Loss of maternal allele 49 / + ND 50 ND + ND 51 ND + ND 52 ND + Loss of maternal allele Rare nonadjacent large islet cell nuclei 53 ND + Loss of maternal allele Focal lesion occupies large area of pancreas All 10 pancreatic specimens studied from patients with diffuse hyperinsulinism did not show loss of p57kip2 labeling of the islet cell nuclei (data not shown). Login to comment

PMID: 24399968 [PubMed] Martin GM et al: "Pharmacological rescue of trafficking-impaired ATP-sensitive potassium channels."

No. Sentence Comment

218 Mutation Domain Rescue Rescue Gating References by SU by CBZ property SUR1 G7R TMD0 Yes Yes Normal Yan et al., 2007 N24K TMD0 Yes Yes Normal Yan et al., 2007 F27S TMD0 Yes Yes Normal Yan et al., 2007 R74W TMD0 Yes Yes ATP-insensitive Yan et al., 2007 A116P TMD0 Yes Yes Normal Yan et al., 2004 E128K TMD0 Yes Yes ATP-insensitive Yan et al., 2007 V187D TMD0 Yes Yes Normal Yan et al., 2004 R495Q TMD1 Yes Yes Unknown Yan et al., 2007 E501K TMD1 Yes Yes Unknown Yan et al., 2007 L503P TMD1 No No Unknown Yan et al., 2007 F686S NBD1 No No Unknown Yan et al., 2007 G716V NBD1 No No Unknown Yan et al., 2007 E1324K TMD2 N.D.3 N.D. Login to comment