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

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

Submit Data | Help | Video Tutorials | News | Publications | Download | REST API | Citing RGD | Contact

Advanced Search (OLGA)

General

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.

Only show annotations with direct experimental evidence (0 objects hidden)

Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
ALAS2	Human	Erythropoietic Protoporphyria, X-Linked Dominant	disease_progression	IAGP		DNA:deletions:exon: c.1699-1700delAT, c.1706-1709delAGTG (human)	RGD
Alas2	Rat	Erythropoietic Protoporphyria, X-Linked Dominant	disease_progression	ISO	RGD:736755	DNA:deletions:exon: c.1699-1700delAT, c.1706-1709delAGTG (human)	RGD
Alas2	Mouse	Erythropoietic Protoporphyria, X-Linked Dominant	disease_progression	ISO	RGD:736755	DNA:deletions:exon: c.1699-1700delAT, c.1706-1709delAGTG (human)	RGD

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)