RGD Reference Report - C-terminal deletions in the ALAS2 gene lead to gain of function and cause X-linked dominant protoporphyria without anemia or iron overload. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources
Advanced Search (OLGA)

C-terminal deletions in the ALAS2 gene lead to gain of function and cause X-linked dominant protoporphyria without anemia or iron overload.

Authors: Whatley, Sharon D  Ducamp, Sarah  Gouya, Laurent  Grandchamp, Bernard  Beaumont, Carole  Badminton, Michael N  Elder, George H  Holme, S Alexander  Anstey, Alexander V  Parker, Michelle  Corrigall, Anne V  Meissner, Peter N  Hift, Richard J  Marsden, Joanne T  Ma, Yun  Mieli-Vergani, Giorgina  Deybach, Jean-Charles  Puy, Hervé 
Citation: Whatley SD, etal., Am J Hum Genet. 2008 Sep;83(3):408-14. doi: 10.1016/j.ajhg.2008.08.003. Epub 2008 Sep 4.
RGD ID: 18337287
Pubmed: PMID:18760763   (View Abstract at PubMed)
PMCID: PMC2556430   (View Article at PubMed Central)
DOI: DOI:10.1016/j.ajhg.2008.08.003   (Journal Full-text)

All reported mutations in ALAS2, which encodes the rate-regulating enzyme of erythroid heme biosynthesis, cause X-linked sideroblastic anemia. We describe eight families with ALAS2 deletions, either c.1706-1709 delAGTG (p.E569GfsX24) or c.1699-1700 delAT (p.M567EfsX2), resulting in frameshifts that lead to replacement or deletion of the 19-20 C-terminal residues of the enzyme. Prokaryotic expression studies show that both mutations markedly increase ALAS2 activity. These gain-of-function mutations cause a previously unrecognized form of porphyria, X-linked dominant protoporphyria, characterized biochemically by a high proportion of zinc-protoporphyrin in erythrocytes, in which a mismatch between protoporphyrin production and the heme requirement of differentiating erythroid cells leads to overproduction of protoporphyrin in amounts sufficient to cause photosensitivity and liver disease.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ALAS2HumanErythropoietic Protoporphyria, X-Linked Dominant disease_progressionIAGP DNA:deletions:exon: c.1699-1700delAT and c.1706-1709delAGTG (human)RGD 
Alas2RatErythropoietic Protoporphyria, X-Linked Dominant disease_progressionISOALAS2 (Homo sapiens)DNA:deletions:exon: c.1699-1700delAT and c.1706-1709delAGTG (human)RGD 
Alas2MouseErythropoietic Protoporphyria, X-Linked Dominant disease_progressionISOALAS2 (Homo sapiens)DNA:deletions:exon: c.1699-1700delAT and c.1706-1709delAGTG (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Alas2  (5'-aminolevulinate synthase 2)

Genes (Mus musculus)
Alas2  (aminolevulinic acid synthase 2, erythroid)

Genes (Homo sapiens)
ALAS2  (5'-aminolevulinate synthase 2)


Additional Information