DTNBP1 was first reported in relation to autosomal recessive Hermansky-Pudlak syndrome 7 in 2003 (PMID: 12923531). At least four unique variants (two nonsense and two frameshift variants) have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data and experimental data. Variants in this gene have been reported in at least seven probands in five publications (PMIDs: 23364359, 28259707, 30990103, 31898847, 29345414). This gene-disease relationship is supported by its protein interactions with components of BLOC-1, which regulates trafficking to lysosome-related organelles [PMID: 12923531], the biochemical function that expressing no dysbindin protein had much fewer melanosomes in the retinal pigment epithelium, and choroid [PMID: 12923531], functional alteration in the patient cells showing the negligible of the DTNBP1 protein level [PMID: 28259707] and a mouse model with the disruption of DTNBP1 protein expression had a severe simultaneous defect in melanosomes, lysosomes and/or platelet dense granules which mimic human Hermansky-Pudlak syndrome and transgenic mice carrying the entire DTNBP1 genomic region could rescue the phenotypes in the mice [PMID:1936982]. In summary, there is definitive evidence to support this gene-disease relationship and has been upheld over time.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. The GenCC does not independently verify the submitted information. Though the information is obtained from sources believed to be reliable, no warranty, expressed or implied, is made regarding accuracy, adequacy, completeness, reliability or usefulness of any information. This disclaimer applies to both isolated and aggregate uses of the information. The information is provided on an "as is" basis, collected through periodic submission and therefore may not represent the most up-to-date information from the submitters. If you have questions about the medical relevance of information contained on this website, please see a healthcare professional; if you have questions about specific gene-disease claims, please contact the relevant sources; and if you have questions about the representation of the data on this website, please contact gencc@thegencc.org.