| Variant ID | 271 |
|---|---|
| Entrez Gene ID | 2778 |
| Gene | GNAS (GeneCards) |
| Location | hg19 20:57484608-57484608
hg38 20:58909553-58909553 |
| Disease | Pseudohypoparathyroidism type1a (view all the variants in this disease) |
| Method | ABI3100 |
| Mutation(HGVS format) | NC_000020.10:g.57484608 C>T (Genome Assembly: hg19) |
| Exon or Intron | Exon |
|---|---|
| Exon number | 9 |
| Position in protein | 231 |
| Amino acid changes in protein | R > H |
| Position in cDNA | 692 |
| Changes in cDNA | G > A |
| mRNA accession | NM_000516.4 |
| mRNA length | 1185 |
| Reference length | 63025520 |
| MAF in gnomAD genome (version 2.0.1) | 0 |
|---|---|
| EIGEN score | 1.0041 |
| CADD Raw score (version 1.3) | 7.447451 (Deleterious) |
| FATHMM raw prediction score | 0.99658 (Tolerated) |
| SIFT score | 0 (Deleterious) |
| LRT score | 0 (Deleterious) |
| MutationTaster score | 1 (Deleterious) |
| MutatioinAssessor score | 4.695 (Deleterious) |
| PROVEAN score | -6.44 (Deleterious) |
| MetaSVM score | 1.082 (Deleterious) |
| MetaLR score | 0.927 (Deleterious) |
| MCAP score | 0.845 (Deleterious) |
| FitCons score | 0.722 (Highly Significant p < 0.003 ) |
| Genomic Evolutionary Rate Profiling (GERP) score | 5.51 |
| PhyloP score based on multiple alignment of 100 vertebrates | 9.467 |
| PhastCons score based on multiple alignment of 100 vertebrates | 1 |
| SiPhy log transformed odds ratio on multiple alignment of 29 mammals | 19.771 |
| Deleterious probability by DeFine | 0.9704 (Deleterious) |
| Entrez Gene ID | 2778 (NCBI Gene) |
|---|---|
| Official Gene Symbol | GNAS (GeneCards) |
| Number of variants in GNAS in this database | 13 (view all the variants) |
| Full name | GNAS complex locus |
| Band | 20q13.32 |
| Other IDs | Vega: OTTHUMG00000033069 OMIM: 139320 HGNC: HGNC:4392 Ensembl: ENSG00000087460 |
| Other names | AHO, GSA, GSP, POH, GPSA, NESP, SCG6, SgVI, GNAS1, PITA3, C20orf45 |
| Summary | This locus has a highly complex imprinted expression pattern. It gives rise to maternally, paternally, and biallelically expressed transcripts that are derived from four alternative promoters and 5' exons. Some transcripts contain a differentially methylated region (DMR) at their 5' exons, and this DMR is commonly found in imprinted genes and correlates with transcript expression. An antisense transcript is produced from an overlapping locus on the opposite strand. One of the transcripts produced from this locus, and the antisense transcript, are paternally expressed noncoding RNAs, and may regulate imprinting in this region. In addition, one of the transcripts contains a second overlapping ORF, which encodes a structurally unrelated protein - Alex. Alternative splicing of downstream exons is also observed, which results in different forms of the stimulatory G-protein alpha subunit, a key element of the classical signal transduction pathway linking receptor-ligand interactions with the activation of adenylyl cyclase and a variety of cellular reponses. Multiple transcript variants encoding different isoforms have been found for this gene. Mutations in this gene result in pseudohypoparathyroidism type 1a, pseudohypoparathyroidism type 1b, Albright hereditary osteodystrophy, pseudopseudohypoparathyroidism, McCune-Albright syndrome, progressive osseus heteroplasia, polyostotic fibrous dysplasia of bone, and some pituitary tumors. [provided by RefSeq, Aug 2012] |
| Individual ID | 20979189.01 (view all the variants in this individual) |
|---|---|
| Pubmed ID | 20979189 |
| Whose mosaic mutation | Mother |
| Phenotype | 2 |
| Number of affected children | 2 ( male: 2; ) |
| Disease | Pseudohypoparathyroidism type1a (view all the variants in this disease) |
| OMIM ID | 103580 |
| Pubmed ID | 20979189 |
|---|---|
| Title | Pseudohypoparathyroidism Type 1a and the GNAS p.R231H Mutation: Somatic Mosaicism in a Mother With Two Affected Sons |
| Journal | American Journal of Medical Genetics |
| Publication date | 2010.11 |
| Disease | Pseudohypoparathyroidism Type 1a |
| Number of cases | Female cases: 1; |