HPS1 gene: MedlinePlus Genetics (original) (raw)
HPS1 biogenesis of lysosomal organelles complex 3 subunit 1
Normal Function
The HPS1 gene provides instructions for making a protein that forms part of a complex called biogenesis of lysosome-related organelles complex-3 (BLOC-3). This complex plays a role in the formation of a group of cellular structures called lysosome-related organelles (LROs). In particular, BLOC-3 helps turn on the process by which necessary proteins are transported to LROs during their formation. LROs are very similar to compartments within the cell called lysosomes, which digest and recycle materials. However, LROs perform specialized functions and are found only in certain cell types.
Within pigment-producing cells (melanocytes), LROs called melanosomes produce and distribute melanin, which is the substance that gives skin, hair, and eyes their color. A different type of LRO is found in platelets, the blood cells involved in normal blood clotting. These LROs, called dense granules, release chemical signals that cause platelets to stick together and form a blood clot. LROs are also found in other specialized cells, including certain cells of the lungs.
Health Conditions Related to Genetic Changes
Hermansky-Pudlak syndrome
At least 31 mutations in the HPS1 gene have been found to cause Hermansky-Pudlak syndrome type 1. Individuals with this form of the condition typically have oculocutaneous albinism, a condition characterized by fair skin, light-colored hair and eyes, and poor vision. They may also have bleeding problems and a severe lung disease called pulmonary fibrosis.
The HPS1 gene mutations that cause Hermansky-Pudlak syndrome type 1 impair the normal function of BLOC-3, disrupting the size, structure, and function of LROs in cells throughout the body. The most common mutation causes a duplication of genetic material within the HPS1 gene and is found in people from northwest Puerto Rico. Specifically, this mutation results in an extra 16 DNA building blocks (nucleotides) within the gene (written as 1470_1486dup16).
Because the abnormal melanosomes do not distribute melanin properly, people with Hermansky-Pudlak syndrome have unusually light coloring of the skin, hair, and eyes. The absence of dense granules within platelets leads to bleeding problems in affected individuals. Pulmonary fibrosis may also develop due to abnormal LROs in certain lung cells.
More About This Health Condition
Other Names for This Gene
- BLOC3S1
- Hermansky-Pudlak syndrome 1
- Hermansky-Pudlak syndrome 1 protein
- Hermansky-Pudlak syndrome 1 protein isoform a
- Hermansky-Pudlak syndrome 1 protein isoform c
- Hermansky-Pudlak syndrome type 1
- HPS
- HPS1_HUMAN
- MGC5277
References
- Carmona-Rivera C, Simeonov DR, Cardillo ND, Gahl WA, Cadilla CL. A divalent interaction between HPS1 and HPS4 is required for the formation of the biogenesis of lysosome-related organelle complex-3 (BLOC-3). Biochim Biophys Acta. 2013 Mar;1833(3):468-78. doi: 10.1016/j.bbamcr.2012.10.019. Epub 2012 Oct 23. Citation on PubMed or Free article on PubMed Central
- Dessinioti C, Stratigos AJ, Rigopoulos D, Katsambas AD. A review of genetic disorders of hypopigmentation: lessons learned from the biology of melanocytes. Exp Dermatol. 2009 Sep;18(9):741-9. doi: 10.1111/j.1600-0625.2009.00896.x. Epub 2009 Jun 23. Citation on PubMed
- Gahl WA, Brantly M, Kaiser-Kupfer MI, Iwata F, Hazelwood S, Shotelersuk V, Duffy LF, Kuehl EM, Troendle J, Bernardini I. Genetic defects and clinical characteristics of patients with a form of oculocutaneous albinism (Hermansky-Pudlak syndrome). N Engl J Med. 1998 Apr 30;338(18):1258-64. doi: 10.1056/NEJM199804303381803. Citation on PubMed
- Gerondopoulos A, Langemeyer L, Liang JR, Linford A, Barr FA. BLOC-3 mutated in Hermansky-Pudlak syndrome is a Rab32/38 guanine nucleotide exchange factor. Curr Biol. 2012 Nov 20;22(22):2135-9. doi: 10.1016/j.cub.2012.09.020. Epub 2012 Oct 18. Citation on PubMed or Free article on PubMed Central
- Huizing M, Helip-Wooley A, Westbroek W, Gunay-Aygun M, Gahl WA. Disorders of lysosome-related organelle biogenesis: clinical and molecular genetics. Annu Rev Genomics Hum Genet. 2008;9:359-86. doi: 10.1146/annurev.genom.9.081307.164303. Citation on PubMed or Free article on PubMed Central
- Huizing M, Parkes JM, Helip-Wooley A, White JG, Gahl WA. Platelet alpha granules in BLOC-2 and BLOC-3 subtypes of Hermansky-Pudlak syndrome. Platelets. 2007 Mar;18(2):150-7. doi: 10.1080/13576500600936039. Citation on PubMed
- Ito S, Suzuki T, Inagaki K, Suzuki N, Takamori K, Yamada T, Nakazawa M, Hatano M, Takiwaki H, Kakuta Y, Spritz RA, Tomita Y. High frequency of Hermansky-Pudlak syndrome type 1 (HPS1) among Japanese albinism patients and functional analysis of HPS1 mutant protein. J Invest Dermatol. 2005 Oct;125(4):715-20. doi: 10.1111/j.0022-202X.2005.23884.x. Citation on PubMed
- Li W, Feng Y, Hao C, Guo X, Cui Y, He M, He X. The BLOC interactomes form a network in endosomal transport. J Genet Genomics. 2007 Aug;34(8):669-82. doi: 10.1016/S1673-8527(07)60076-9. Citation on PubMed
- Santiago Borrero PJ, Rodriguez-Perez Y, Renta JY, Izquierdo NJ, Del Fierro L, Munoz D, Molina NL, Ramirez S, Pagan-Mercado G, Ortiz I, Rivera-Caragol E, Spritz RA, Cadilla CL. Genetic testing for oculocutaneous albinism type 1 and 2 and Hermansky-Pudlak syndrome type 1 and 3 mutations in Puerto Rico. J Invest Dermatol. 2006 Jan;126(1):85-90. doi: 10.1038/sj.jid.5700034. Citation on PubMed or Free article on PubMed Central