3k7i

Structural highlights

Disease

IHH_HUMAN Brachydactyly type A1;Acrocapitofemoral dysplasia. Defects in IHH are the cause of brachydactyly type A1 (BDA1) [MIM:112500. BDA1 is an autosomal dominant disorder characterized by middle phalanges of all the digits rudimentary or fused with the terminal phalanges. The proximal phalanges of the thumbs and big toes are short.^{[1] [2]} Defects in IHH are a cause of acrocapitofemoral dysplasia (ACFD) [MIM:607778. ACFD is a disorder characterized by short stature of variable severity with postnatal onset. The most constant radiographic abnormalities are observed in the tubular bones of the hands and in the proximal part of the femur. Cone-shaped epiphyses or a similar epiphyseal configuration with premature epimetaphyseal fusion result in shortening of the skeletal components involved. Cone-shaped epiphyses were also present to a variable extent at the shoulders, knees, and ankles.^[3]

Function

IHH_HUMAN Intercellular signal essential for a variety of patterning events during development. Binds to the patched (PTC) receptor, which functions in association with smoothened (SMO), to activate the transcription of target genes. Implicated in endochondral ossification: may regulate the balance between growth and ossification of the developing bones. Induces the expression of parathyroid hormone-related protein (PTHRP) (By similarity).

References

1. ↑ Gao B, Guo J, She C, Shu A, Yang M, Tan Z, Yang X, Guo S, Feng G, He L. Mutations in IHH, encoding Indian hedgehog, cause brachydactyly type A-1. Nat Genet. 2001 Aug;28(4):386-8. PMID:11455389 doi:http://dx.doi.org/10.1038/ng577
2. ↑ McCready ME, Sweeney E, Fryer AE, Donnai D, Baig A, Racacho L, Warman ML, Hunter AG, Bulman DE. A novel mutation in the IHH gene causes brachydactyly type A1: a 95-year-old mystery resolved. Hum Genet. 2002 Oct;111(4-5):368-75. Epub 2002 Sep 7. PMID:12384778 doi:http://dx.doi.org/10.1007/s00439-002-0815-2
3. ↑ Hellemans J, Coucke PJ, Giedion A, De Paepe A, Kramer P, Beemer F, Mortier GR. Homozygous mutations in IHH cause acrocapitofemoral dysplasia, an autosomal recessive disorder with cone-shaped epiphyses in hands and hips. Am J Hum Genet. 2003 Apr;72(4):1040-6. Epub 2003 Mar 11. PMID:12632327