3hhr

Structural highlights

Disease

[SOMA_HUMAN] Defects in GH1 are a cause of growth hormone deficiency isolated type 1A (IGHD1A) [MIM:262400]; also known as pituitary dwarfism I. IGHD1A is an autosomal recessive deficiency of GH which causes short stature. IGHD1A patients have an absence of GH with severe dwarfism and often develop anti-GH antibodies when given exogenous GH.^[1] Defects in GH1 are a cause of growth hormone deficiency isolated type 1B (IGHD1B) [MIM:612781]; also known as dwarfism of Sindh. IGHD1B is an autosomal recessive deficiency of GH which causes short stature. IGHD1B patients have low but detectable levels of GH. Dwarfism is less severe than in IGHD1A and patients usually respond well to exogenous GH. Defects in GH1 are the cause of Kowarski syndrome (KWKS) [MIM:262650]; also known as pituitary dwarfism VI.^{[2] [3] [4]} Defects in GH1 are a cause of growth hormone deficiency isolated type 2 (IGHD2) [MIM:173100]. IGHD2 is an autosomal dominant deficiency of GH which causes short stature. Clinical severity is variable. Patients have a positive response and immunologic tolerance to growth hormone therapy. [GHR_HUMAN] Defects in GHR are a cause of Laron syndrome (LARS) [MIM:262500]. A severe form of growth hormone insensitivity characterized by growth impairment, short stature, dysfunctional growth hormone receptor, and failure to generate insulin-like growth factor I in response to growth hormone.^{[5] [6] [7] [8] [9] [10] [11] [12] [13] [14]} Defects in GHR may be a cause of idiopathic short stature autosomal (ISSA) [MIM:604271]. Short stature is defined by a subnormal rate of growth.^[15]

Function

[SOMA_HUMAN] Plays an important role in growth control. Its major role in stimulating body growth is to stimulate the liver and other tissues to secrete IGF-1. It stimulates both the differentiation and proliferation of myoblasts. It also stimulates amino acid uptake and protein synthesis in muscle and other tissues. [GHR_HUMAN] Receptor for pituitary gland growth hormone involved in regulating postnatal body growth. On ligand binding, couples to the JAK2/STAT5 pathway (By similarity). The soluble form (GHBP) acts as a reservoir of growth hormone in plasma and may be a modulator/inhibitor of GH signaling. Isoform 2 up-regulates the production of GHBP and acts as a negative inhibitor of GH signaling.

Evolutionary Conservation

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

See Also

• Human growth hormone

References

1. ↑ Igarashi Y, Ogawa M, Kamijo T, Iwatani N, Nishi Y, Kohno H, Masumura T, Koga J. A new mutation causing inherited growth hormone deficiency: a compound heterozygote of a 6.7 kb deletion and a two base deletion in the third exon of the GH-1 gene. Hum Mol Genet. 1993 Jul;2(7):1073-4. PMID:8364549
2. ↑ Takahashi Y, Kaji H, Okimura Y, Goji K, Abe H, Chihara K. Brief report: short stature caused by a mutant growth hormone. N Engl J Med. 1996 Feb 15;334(7):432-6. PMID:8552145 doi:http://dx.doi.org/10.1056/NEJM199602153340704
3. ↑ Takahashi Y, Shirono H, Arisaka O, Takahashi K, Yagi T, Koga J, Kaji H, Okimura Y, Abe H, Tanaka T, Chihara K. Biologically inactive growth hormone caused by an amino acid substitution. J Clin Invest. 1997 Sep 1;100(5):1159-65. PMID:9276733 doi:10.1172/JCI119627
4. ↑ Petkovic V, Besson A, Thevis M, Lochmatter D, Eble A, Fluck CE, Mullis PE. Evaluation of the biological activity of a growth hormone (GH) mutant (R77C) and its impact on GH responsiveness and stature. J Clin Endocrinol Metab. 2007 Aug;92(8):2893-901. Epub 2007 May 22. PMID:17519310 doi:10.1210/jc.2006-2238
5. ↑ Amselem S, Duquesnoy P, Attree O, Novelli G, Bousnina S, Postel-Vinay MC, Goossens M. Laron dwarfism and mutations of the growth hormone-receptor gene. N Engl J Med. 1989 Oct 12;321(15):989-95. PMID:2779634
6. ↑ Kou K, Lajara R, Rotwein P. Amino acid substitutions in the intracellular part of the growth hormone receptor in a patient with the Laron syndrome. J Clin Endocrinol Metab. 1993 Jan;76(1):54-9. PMID:8421103
7. ↑ Amselem S, Duquesnoy P, Duriez B, Dastot F, Sobrier ML, Valleix S, Goossens M. Spectrum of growth hormone receptor mutations and associated haplotypes in Laron syndrome. Hum Mol Genet. 1993 Apr;2(4):355-9. PMID:8504296
8. ↑ Edery M, Rozakis-Adcock M, Goujon L, Finidori J, Levi-Meyrueis C, Paly J, Djiane J, Postel-Vinay MC, Kelly PA. Lack of hormone binding in COS-7 cells expressing a mutated growth hormone receptor found in Laron dwarfism. J Clin Invest. 1993 Mar;91(3):838-44. PMID:8450064 doi:http://dx.doi.org/10.1172/JCI116304
9. ↑ Duquesnoy P, Sobrier ML, Duriez B, Dastot F, Buchanan CR, Savage MO, Preece MA, Craescu CT, Blouquit Y, Goossens M, et al.. A single amino acid substitution in the exoplasmic domain of the human growth hormone (GH) receptor confers familial GH resistance (Laron syndrome) with positive GH-binding activity by abolishing receptor homodimerization. EMBO J. 1994 Mar 15;13(6):1386-95. PMID:8137822
10. ↑ Sobrier ML, Dastot F, Duquesnoy P, Kandemir N, Yordam N, Goossens M, Amselem S. Nine novel growth hormone receptor gene mutations in patients with Laron syndrome. J Clin Endocrinol Metab. 1997 Feb;82(2):435-7. PMID:9024232
11. ↑ Walker JL, Crock PA, Behncken SN, Rowlinson SW, Nicholson LM, Boulton TJ, Waters MJ. A novel mutation affecting the interdomain link region of the growth hormone receptor in a Vietnamese girl, and response to long-term treatment with recombinant human insulin-like growth factor-I and luteinizing hormone-releasing hormone analogue. J Clin Endocrinol Metab. 1998 Jul;83(7):2554-61. PMID:9661642
12. ↑ Wojcik J, Berg MA, Esposito N, Geffner ME, Sakati N, Reiter EO, Dower S, Francke U, Postel-Vinay MC, Finidori J. Four contiguous amino acid substitutions, identified in patients with Laron syndrome, differently affect the binding affinity and intracellular trafficking of the growth hormone receptor. J Clin Endocrinol Metab. 1998 Dec;83(12):4481-9. PMID:9851797
13. ↑ Enberg B, Luthman H, Segnestam K, Ritzen EM, Sundstrom M, Norstedt G. Characterisation of novel missense mutations in the GH receptor gene causing severe growth retardation. Eur J Endocrinol. 2000 Jul;143(1):71-6. PMID:10870033
14. ↑ Jorge AA, Souza SC, Arnhold IJ, Mendonca BB. The first homozygous mutation (S226I) in the highly-conserved WSXWS-like motif of the GH receptor causing Laron syndrome: supression of GH secretion by GnRH analogue therapy not restored by dihydrotestosterone administration. Clin Endocrinol (Oxf). 2004 Jan;60(1):36-40. PMID:14678285
15. ↑ Goddard AD, Covello R, Luoh SM, Clackson T, Attie KM, Gesundheit N, Rundle AC, Wells JA, Carlsson LM. Mutations of the growth hormone receptor in children with idiopathic short stature. The Growth Hormone Insensitivity Study Group. N Engl J Med. 1995 Oct 26;333(17):1093-8. PMID:7565946
16. ↑ de Vos AM, Ultsch M, Kossiakoff AA. Human growth hormone and extracellular domain of its receptor: crystal structure of the complex. Science. 1992 Jan 17;255(5042):306-12. PMID:1549776