3n1f

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] [CDON_HUMAN] Defects in CDON are the cause of holoprosencephaly type 11 (HPE11) [MIM:614226]. HPE11 is a structural anomaly of the brain, in which the developing forebrain fails to correctly separate into right and left hemispheres. Holoprosencephaly is genetically heterogeneous and associated with several distinct facies and phenotypic variability.

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). [CDON_HUMAN] Component of a cell-surface receptor complex that mediates cell-cell interactions between muscle precursor cells. Promotes differentiation of myogenic cells (By similarity).

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

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
4. ↑ Kavran JM, Ward MD, Oladosu OO, Mulepati S, Leahy DJ. All mammalian Hedgehog proteins interact with cell adhesion molecule, down-regulated by oncogenes (CDO) and brother of CDO (BOC) in a conserved manner. J Biol Chem. 2010 Aug 6;285(32):24584-90. Epub 2010 Jun 1. PMID:20519495 doi:10.1074/jbc.M110.131680