ABCMdb

ABCC9 p.Arg1154Gln

None has been submitted yet.

Publications

PMID: 22608503 [PubMed] van Bon BW et al: "Cantu syndrome is caused by mutations in ABCC9."

No. Sentence Comment

19 Phenotype of Individuals with Cantu &#b4; Syndrome Clinical Features Affected Individuals 1 2a 2b 2c 3 4 5 6 7 8a 8b 9a 9b 10 Gender M F F F M F M F M F M M F M Mutation (cDNA) 3460C>T 3461G>A 3461G>A 3461G>A 3461G>A 3460C>T 3460C>T 3128G>A 3461G>T 1433C>T 1433C>T - - - Alteration (protein) Arg1154Trp Arg1154Gln Arg1154Gln Arg1154Gln Arg1154Gln Arg1154Trp Arg1154Trp Cys1043Tyr Arg1154Gln Ala478Val Ala478Val - - - Inherited de novo inherited inherited de novo de novo de novo de novo de novo inherited Consanguinity &#fe; - - - - - &#fe; - - - &#fe; &#fe; &#fe; - Age at evaluation 4 m 16 yrs 10 yrs 39 yrs 8 yrs 21 yrs 3.5 m 4.5 yrs 9.8 yrs 4 m 32 yrs 6 yrs 4 yrs 3 m Alive - &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; - &#fe; Congenital hypertrichosis &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; Macrosomia at birth &#fe; - &#fe; &#fe; - &#fe; - &#fe; - &#fe; &#fe; - - &#fe; Macrocephaly &#fe; &#fe; &#fe; &#fe; &#fe; - &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; ID* and/or developmental delay - - - - &#fe; - &#fe; - - &#fe; - &#fe; &#fe; &#fe; Facial Features Coarse face &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; Epicanthal folds &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; - Abundant and/or curly eyelashes &#fe; &#fe; &#fe; - &#fe; - &#fe; &#fe; &#fe; &#fe; - &#fe; &#fe; &#fe; Broad and/or flat nasal bridge &#fe; &#fe; &#fe; &#fe; &#fe; - &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; Small nose and/or anteverted nostrils &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; - - - &#fe; Prominent mouth and/or thick lips &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; Long philtrum &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; &#fe; High and/or narrow palate &#fe; &#fe; &#fe; &#fe; - &#fe; &#fe; - - - &#fe; &#fe; &#fe; - Macroglossy &#fe; &#fe; &#fe; &#fe; - &#fe; &#fe; - - - &#fe; - - - Anterior open bite - &#fe; &#fe; - - &#fe; - - - - - - - Gingival hyperplasia &#fe; &#fe; &#fe; &#fe; - &#fe; &#fe; - - &#fe; - - - - Short neck - - - &#fe; &#fe; - &#fe; &#fe; &#fe; - - &#fe; &#fe; &#fe; (Continued on next page) Table 1. Login to comment

PMID: 22610116 [PubMed] Harakalova M et al: "Dominant missense mutations in ABCC9 cause Cantu syndrome."

No. Sentence Comment

31 The encoded p.Arg1154Gln variant is most likely damaging (predicted to be probably damaging, deleterious and deleterious by Polyphen-2, Condel and SIFT, respectively, using the Variant Effect Predictor tool (ENSEMBL version 67)) and highly conserved (Genomic Evolutionary Rate Profiling (GERP) scores of 4.33 (35 way)). Login to comment
59 The nucleotide-binding Table 1 Summary of detected heterozygous missense mutations in ABCC9 Subject Chr. Genomic alterationa cDNA alteration Protein alteration 9 12 g.22086822C>T c.178C>T p.His60Tyr 7 12 g.22068797C>A c.621C>A p.Asp207Glu 10 12 g.22063786G>T c.1138G>T p.Gly380Cys 5 12 g.22063116C>T c.1295C>T p.Pro432Leu 12 12 g.21998575T>C c.3058T>C p.Ser1020Pro 16 12 g.21997830T>C c.3116>C p.Phe1039Ser 15 12 g.21997785C>A c.3161>A p.Ser1054Tyr 2,3 (child and mother) 12 g.21995374G>A c.3347G>A p.Arg1116His 14 12 g.21995375C>T c.3346C>T p.Arg1116Cys 4 12 g.21995261C>T c.3460C>T p.Arg1154Trp 1,6,8 12 g.21995260G>A c.3461G>A p.Arg1154Gln Chr., chromosome. Login to comment
62 a b NBD2 NBD1 TMD2 TMD1 TMD0 p.His60Tyr p.Asp207Glu p.Gly380Cys p.Pro432Leu p.Ser1020Pro p.Phe1039Ser p.Ser1054Tyr p.Arg1116Cys p.Arg1116His p.Arg1116His* p.Arg1154Gln p.Arg1154Gln p.Arg1154Gln p.Arg1154Trp Figure 1 Clinical presentation of subjects with Cant&#fa; syndrome and mutations in ABCC9. Login to comment
81 In contrast, ABCC9 p.Arg1154Gln (0.88 &#b1; 0.19 and 0.76 &#b1; 0.12 mM for inward and outward components, respectively), ABCC9 p.Pro432Leu (1.18 &#b1; 0.18 and 1.25 &#b1; 0.16 mM) and ABCC9 p.Arg1116His(0.28&#b1;0.05and0.24&#b1;0.04mM)mutantchannelsshowed reduced ATP sensitivity. Login to comment
88 The similarities between the phenotypic characteristics of individuals with Cant&#fa; -2,000 -1,500 -1,000 -500 0 500 1,000 1,500 -2,000 -1,500 -1,000 -500 0 500 1,000 1,500 -2,000 -1,500 -1,000 -500 0 500 1,000 1,500 -2,000 -1,500 -1,000 -500 0 500 1,000 1,500 WT p.Pro432Leu p.Arg1116His p.Arg1154Gln C 0.1 1.0 10 C, 0.1 1.0 10 C 0.1 1.0 10 C 0.1 1.0 10 0.0 0.01 0.1 1 10 ATP (mM) 0 20 40 60 80 100 Remaining current (%) Inward 0.0 0.01 0.1 1 10 ATP (mM) Outward 0 20 40 60 80 100 Remaining current (%) WT p.Arg1154Gln IC 50 0.88 &#b1; 0.19* p.Pro432Leu IC 50 1.18 &#b1; 0.18** p.Arg1116His IC 50 0.28 &#b1; 0.05*** WT IC 50 0.07 &#b1; 0.01 p.Arg1154Gln IC 50 0.76 &#b1; 0.12* p.Pro432Leu IC 50 1.25 &#b1; 0.16** p.Arg1116His IC 50 0.24 &#b1; 0.04*** Asp207 Arg1154 Pro432 Ser1020 Phe1039 Arg1116 Ser1054 Gly380 Current (pA) Current (pA) Current (pA) Current (pA) -100 100 0 Membrane potential (mV) IC 50 0.07 &#b1; 0.01 a b c Figure 2 Topology and biophysical effect of ABCC9 mutations. Login to comment
98 Wild-type ABCC9, n = 8; ABCC9 p.Arg1154Gln, n = 7; ABCC9 p.Pro432Leu, n = 6; ABCC9 p.Arg1116His, n = 5. Login to comment
227 Nucleotide changes encoding the p.Arg1154Gln, p.Pro432Leu and p.Arg1116His alterations were engineered into the ABCC9 expression construct using the QuikChange II XL Site-Directed Mutagenesis Kit (Stratagene) and custom-designed mutagenesis primers. Login to comment