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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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HPS6
HPS6 biogenesis of lysosomal organelles complex 2 subunit 3
Chromosome 10 Β· 10q24.32
NCBI Gene: 79803Ensembl: ENSG00000166189.8HGNC: HGNC:18817UniProt: Q86YV9
50PubMed Papers
21Diseases
0Drugs
99Pathogenic Variants
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingGTP-dependent protein bindingsmall GTPase bindinglysosome localizationHermansky-Pudlak syndrome without pulmonary fibrosisHermansky-Pudlak syndromeatrial fibrillationgenetic disorder
✦AI Summary

HPS6 is a subunit of the BLOC-2 (biogenesis of lysosomal organelles complex-2) protein complex that regulates lysosome-related organelle biogenesis and function 1. The protein acts as a cargo adapter linking lysosomes to the dynein-dynactin motor complex, mediating retrograde transport of lysosomes from the cell periphery to the perinuclear region 2. This perinuclear positioning is critical for lysosome maturation, acidification, degradative capacity, and fusion with late endosomes 2. HPS6 functions within a stable 340 kDa BLOC-2 complex alongside HPS3 and HPS5 proteins, with specific amino acid residues essential for complex assembly 13. The protein is particularly important for biogenesis of specialized organelles including melanosomes and platelet dense granules 1. Mutations in HPS6 cause Hermansky-Pudlak syndrome type 6 (HPS6), a rare autosomal recessive disorder characterized by oculocutaneous albinism, platelet dysfunction with deficient dense granules, and variable systemic manifestations including pulmonary fibrosis and immunodeficiency 456. HPS6 variants show clustering in CpG islands and specific protein structural regions, though no clear genotype-phenotype correlation has been established 6. Early molecular diagnosis via genomic sequencing is essential for clinical management 7.

Sources cited
1
HPS6 is a BLOC-2 complex component; protein interaction requirements and phenotypic effects in mutant mice
PMID: 14718540
2
HPS6 interacts with dynactin p150Glued to mediate lysosomal retrograde trafficking and perinuclear positioning necessary for maturation and function
PMID: 25189619
3
BLOC-2 complex composition and biochemical characterization including HPS6 as a peripheral membrane protein subunit
PMID: 15030569
4
HPS6 mutations cause Hermansky-Pudlak syndrome type 6 with oculocutaneous albinism, platelet dysfunction, and variable systemic features
PMID: 36162005
5
HPS6 is a rare subtype of syndromic oculocutaneous albinism with bleeding tendency and systemic complications
PMID: 32969595
6
HPS6 variant profile, clustering in CpG islands and structural regions, and lack of genotype-phenotype correlation
PMID: 38091959
7
Novel HPS6 mutations identified through whole-exome sequencing in patients with ocular albinism and absent platelet dense bodies
PMID: 27225848
Disease Associationsβ“˜21
Hermansky-Pudlak syndrome without pulmonary fibrosisOpen Targets
0.78Strong
Hermansky-Pudlak syndromeOpen Targets
0.74Strong
atrial fibrillationOpen Targets
0.28Weak
genetic disorderOpen Targets
0.19Weak
actinic keratosisOpen Targets
0.17Weak
skin cancerOpen Targets
0.15Weak
platelet storage pool deficiencyOpen Targets
0.15Weak
Platelet storage pool diseaseOpen Targets
0.15Weak
Abnormal bleedingOpen Targets
0.11Weak
ThrombocytopeniaOpen Targets
0.11Weak
Griscelli diseaseOpen Targets
0.10Weak
Griscelli disease type 3Open Targets
0.10Suggestive
Griscelli syndrome type 3Open Targets
0.10Suggestive
Microcephaly - albinism - digital anomaliesOpen Targets
0.09Suggestive
microcephaly-albinism-digital anomalies syndromeOpen Targets
0.09Suggestive
Tietz syndromeOpen Targets
0.08Suggestive
uncombable hair syndromeOpen Targets
0.08Suggestive
Griscelli disease type 1Open Targets
0.08Suggestive
Griscelli syndrome type 1Open Targets
0.08Suggestive
oculocutaneous albinism type 3Open Targets
0.08Suggestive
Hermansky-Pudlak syndrome 6UniProt
Pathogenic Variants99
NM_024747.6(HPS6):c.1784G>A (p.Trp595Ter)Pathogenic
Hermansky-Pudlak syndrome 6|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 595
NM_024747.6(HPS6):c.97C>T (p.Arg33Ter)Pathogenic
not provided|Hermansky-Pudlak syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 33
NM_024747.6(HPS6):c.60_64dup (p.Leu22fs)Pathogenic
not provided|Hermansky-Pudlak syndrome|HPS6-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 22
NM_024747.6(HPS6):c.1114C>T (p.Arg372Ter)Pathogenic
not provided|Hermansky-Pudlak syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 372
NM_024747.6(HPS6):c.560dup (p.His187fs)Pathogenic
not provided|Hermansky-Pudlak syndrome 6
β˜…β˜…β˜†β˜†2025β†’ Residue 187
NM_024747.6(HPS6):c.1387C>T (p.Arg463Ter)Pathogenic
not provided|Hermansky-Pudlak syndrome|Hermansky-Pudlak syndrome 6
β˜…β˜…β˜†β˜†2025β†’ Residue 463
NM_024747.6(HPS6):c.706_707del (p.Ser236fs)Pathogenic
Hermansky-Pudlak syndrome|not provided|HPS6-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 236
NM_024747.6(HPS6):c.1789del (p.Ala597fs)Pathogenic
Hermansky-Pudlak syndrome 6|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 597
NM_024747.6(HPS6):c.1513C>T (p.Gln505Ter)Pathogenic
not provided|Hermansky-Pudlak syndrome 6
β˜…β˜…β˜†β˜†2025β†’ Residue 505
NM_024747.6(HPS6):c.1030G>T (p.Glu344Ter)Pathogenic
Hermansky-Pudlak syndrome 6|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 344
NM_024747.6(HPS6):c.466_475dup (p.Phe159fs)Pathogenic
not provided|Hermansky-Pudlak syndrome 6
β˜…β˜…β˜†β˜†2025β†’ Residue 159
NM_024747.6(HPS6):c.503_504del (p.Leu168fs)Pathogenic
not provided|Hermansky-Pudlak syndrome 6
β˜…β˜…β˜†β˜†2025β†’ Residue 168
NM_024747.6(HPS6):c.1054_1055del (p.Arg352fs)Pathogenic
not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 352
NM_024747.6(HPS6):c.27del (p.Leu10fs)Pathogenic
not provided|Hermansky-Pudlak syndrome 6
β˜…β˜…β˜†β˜†2024β†’ Residue 10
NM_024747.6(HPS6):c.155del (p.Val52fs)Pathogenic
Hermansky-Pudlak syndrome|not provided|Hermansky-Pudlak syndrome 6
β˜…β˜…β˜†β˜†2024β†’ Residue 52
NM_024747.6(HPS6):c.779G>A (p.Gly260Glu)Pathogenic
Hermansky-Pudlak syndrome|Hermansky-Pudlak syndrome 6
β˜…β˜…β˜†β˜†2024β†’ Residue 260
NM_024747.6(HPS6):c.1234C>T (p.Gln412Ter)Pathogenic
Hermansky-Pudlak syndrome 6|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 412
NM_024747.6(HPS6):c.1649del (p.Gly550fs)Pathogenic
Hermansky-Pudlak syndrome|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 550
NM_024747.6(HPS6):c.1674del (p.Asn559fs)Pathogenic
not provided|Hermansky-Pudlak syndrome 6
β˜…β˜…β˜†β˜†2024β†’ Residue 559
NM_024747.6(HPS6):c.1711_1712insAG (p.Cys571Ter)Pathogenic
Hermansky-Pudlak syndrome 6|not provided|Hermansky-Pudlak syndrome
β˜…β˜…β˜†β˜†2023β†’ Residue 571
View on ClinVar β†—
Related Genes
BLOC1S1Protein interaction100%TYRP1Protein interaction100%SNAPINProtein interaction100%BLOC1S4Protein interaction100%BLOC1S5Protein interaction100%BLOC1S3Protein interaction91%
Tissue Expression6 tissues
Heart
100%
Lung
86%
Liver
74%
Bone Marrow
71%
Ovary
63%
Brain
43%
Gene Interaction Network
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HPS6BLOC1S1TYRP1SNAPINBLOC1S4BLOC1S5BLOC1S3
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q86YV9
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.15LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.90 [0.71–1.15]
RankingsWhere HPS6 stands among ~20K protein-coding genes
  • #8,823of 20,598
    Most Researched50
  • #788of 5,498
    Most Pathogenic Variants99 Β· top quartile
  • #11,914of 17,882
    Most Constrained (LOEUF)1.15
Genes detectedHPS6
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
PMID: 20301464
1.00
2
A zinc transporter, transmembrane protein 163, is critical for the biogenesis of platelet dense granules.
PMID: 33513603
Blood Β· 2021
0.90
3
Hermansky-Pudlak Syndrome: Spectrum in Oman.
PMID: 36162005
J Pediatr Hematol Oncol Β· 2023
0.80
4
Current landscape of Oculocutaneous Albinism in Japan.
PMID: 32969595
Pigment Cell Melanoma Res Β· 2021
0.70
5
Novel Variants of HPS6 Cause Suspected Ocular Albinism: A Report of 2 Cases and the Profile of HPS6 Variants.
PMID: 38091959
Ophthalmic Res Β· 2024
0.60