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Normal Function
The HPS3 gene provides instructions for making a protein that forms part of a complex called biogenesis of lysosome-related organelles complex-2 (BLOC-2). This complex plays a role in the formation of a group of cellular structures called lysosome-related organelles (LROs). In particular, BLOC-2 controls the sorting and transport of proteins into 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.
Health Conditions Related to Genetic Changes
Hermansky-Pudlak syndrome
At least 7 mutations in the HPS3 gene have been found to cause Hermansky-Pudlak syndrome type 3, which is a mild form of the condition. Affected individuals typically have oculocutaneous albinism, a condition characterized by fair skin, light-colored hair and eyes, and poor vision. They may also have bleeding problems. The HPS3 gene mutations that cause Hermansky-Pudlak syndrome type 3 impair the normal function of BLOC-2, disrupting the size, structure, and function of LROs in cells throughout the body.
One common mutation results in a deletion of genetic material within the HPS3 gene. This deletion includes approximately 3,900 DNA building blocks (nucleotides) and is known as the 3.9kb deletion. It is also written as 339_4260del3904. This mutation, which is found in affected individuals from the central region of Puerto Rico, prevents the production of any HPS3 protein.
Another mutation in the HPS3 gene has been found in people with Central and Eastern European (Ashkenazi) Jewish background. This mutation, called a splice-site mutation, disrupts the way the gene's instructions are used to make the protein. This mutation, which is written as 1163+1G>A, results in an abnormally short protein.
Because the abnormal melanosomes do not distribute melanin properly, people with Hermansky-Pudlak syndrome can develop oculocutaneous albinism. The absence of dense granules within platelets leads to bleeding problems in affected individuals.
More About This Health ConditionOther Names for This Gene
- BLOC2S1
- DKFZp686F0413
- FLJ22704
- Hermansky-Pudlak syndrome 3
- Hermansky-Pudlak syndrome 3 protein
- HPS3_HUMAN
- SUTAL
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Anikster Y, Huizing M, White J, Shevchenko YO, Fitzpatrick DL, Touchman JW, Compton JG, Bale SJ, Swank RT, Gahl WA, Toro JR. Mutation of a new gene causes a unique form of Hermansky-Pudlak syndrome in a genetic isolate of central Puerto Rico. Nat Genet. 2001 Aug;28(4):376-80. doi: 10.1038/ng576. Citation on PubMed
- Bultema JJ, Ambrosio AL, Burek CL, Di Pietro SM. BLOC-2, AP-3, and AP-1 proteins function in concert with Rab38 and Rab32 proteins to mediate protein trafficking to lysosome-related organelles. J Biol Chem. 2012 Jun 1;287(23):19550-63. doi: 10.1074/jbc.M112.351908. Epub 2012 Apr 16. Citation on PubMed or Free article on PubMed Central
- Bultema JJ, Di Pietro SM. Cell type-specific Rab32 and Rab38 cooperate with the ubiquitous lysosome biogenesis machinery to synthesize specialized lysosome-related organelles. Small GTPases. 2013 Jan-Mar;4(1):16-21. doi: 10.4161/sgtp.22349. Epub 2012 Dec 17. 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
- Huizing M, Anikster Y, Fitzpatrick DL, Jeong AB, D'Souza M, Rausche M, Toro JR, Kaiser-Kupfer MI, White JG, Gahl WA. Hermansky-Pudlak syndrome type 3 in Ashkenazi Jews and other non-Puerto Rican patients with hypopigmentation and platelet storage-pool deficiency. Am J Hum Genet. 2001 Nov;69(5):1022-32. doi: 10.1086/324168. Epub 2001 Oct 3. 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
- 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
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