HPS4 Gene: Hermansky-Pudlak Syndrome 4
Biogenesis of lysosome-related organelles complex 3 subunit 2
Gene Information Card
| Symbol | HPS4 |
|---|---|
| Full Name | HPS4, biogenesis of lysosomal organelles complex 3 subunit 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 22q12.1 |
| NCBI Gene ID | 89781 ncbi.nlm.nih.gov/gene/89781 |
| Ensembl ID | ENSG00000100099 |
| UniProt ID | Q9NQG7 |
| OMIM ID | 606682 |
| HGNC ID | 15826 |
| Aliases | BLOC3S2, HPS4A, HPS4B |
Description
The HPS4 gene encodes a component of the biogenesis of lysosome-related organelles complex 3 (BLOC-3), which is essential for the formation and trafficking of lysosome-related organelles such as melanosomes and platelet dense granules. Mutations in HPS4 cause Hermansky-Pudlak syndrome type 4, characterized by oculocutaneous albinism, bleeding diathesis, and pulmonary fibrosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hermansky-Pudlak syndrome 4 (HPS4) | Loss-of-function mutations in HPS4 disrupt BLOC-3 complex assembly, impairing melanosome and dense granule biogenesis. | OMIM #614073; ClinVar pathogenic variants |
| Pulmonary fibrosis (associated with HPS4) | Defective BLOC-3 leads to abnormal surfactant processing and fibrotic lung remodeling. | OMIM #614073; case reports in HPS4 patients |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 8.2 | Medium |
| Spleen | 6.5 | Medium |
| Kidney | 5.1 | Low |
| Liver | 4.3 | Low |
| Skin | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (lung carcinoma) | 7.1 | Moderate expression |
| HEK293 (embryonic kidney) | 5.6 | Low expression |
| HeLa (cervical carcinoma) | 4.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.972_973delCT | Frameshift | Rare | Loss of function; truncation of BLOC-3 subunit |
| c.1303C>T (p.Arg435*) | Nonsense | Rare | Premature stop; loss of function |
| c.1660G>A (p.Gly554Arg) | Missense | Rare | Likely loss of function; disrupts protein folding |
Mutation functional classification
Loss of Function (LOF)
Most HPS4 mutations are loss-of-function, leading to BLOC-3 complex instability and impaired organelle biogenesis.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • BLOC-3 complex (GO:0031083) | • lysosome localization (GO:0032418) |
| • melanosome organization (GO:0032438) | • positive regulation of pigment granule maturation (GO:0035578) |
| • cytoplasm (GO:0005737) |
Pathways
• Biogenesis of lysosome-related organelles complex 3 (BLOC-3) pathway
• Hermansky-Pudlak syndrome pathway
Protein Summary
The HPS4 protein (UniProt Q9NQG7) is a 708-amino acid subunit of the BLOC-3 complex, which also includes HPS1. BLOC-3 acts as a guanine nucleotide exchange factor (GEF) for Rab32 and Rab38, regulating vesicle trafficking to lysosome-related organelles. Loss of HPS4 disrupts melanosome maturation in melanocytes and dense granule formation in platelets, leading to the clinical features of Hermansky-Pudlak syndrome.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HPS4 Knockout HEK293 Cell Line | EDJ-KQ10506 | Human | 89781 | Details Get a Quote |
| HPS4 Knockout A-549 Cell Line | EDJ-KQ37909 | Human | 89781 | Details Get a Quote |
| HPS4 Knockout HCT 116 Cell Line | EDJ-KQ37910 | Human | 89781 | Details Get a Quote |
| HPS4 Knockout HeLa Cell Line | EDJ-KQ37911 | Human | 89781 | Details Get a Quote |
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