PACS1 Gene
Phosphofurin Acidic Cluster Sorting Protein 1
Gene Information Card
| Symbol | PACS1 |
|---|---|
| Full Name | Phosphofurin Acidic Cluster Sorting Protein 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 11q13.1 |
| NCBI Gene ID | 5569 ncbi.nlm.nih.gov/gene/5569 |
| Ensembl ID | ENSG00000175115 |
| UniProt ID | Q6VY07 |
| OMIM ID | 607492 |
| HGNC ID | 8598 |
| Aliases | PACS-1, MRD17 |
Description
The PACS1 gene encodes phosphofurin acidic cluster sorting protein 1, a member of the PACS protein family involved in mediating the localization of trans-Golgi network (TGN) membrane proteins by recognizing acidic cluster sorting motifs. It plays a role in protein trafficking between the TGN and endosomes/lysosomes, and is essential for normal neuronal development. Heterozygous missense mutations in PACS1 cause Schuurs-Hoeijmakers syndrome, a neurodevelopmental disorder characterized by intellectual disability, distinctive facial features, and congenital anomalies.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Schuurs-Hoeijmakers syndrome (PACS1 neurodevelopmental disorder) | Heterozygous missense mutation (c.607C>T, p.Arg203Trp) leads to altered protein sorting and impaired neuronal function | ClinVar, OMIM #615009 |
| Intellectual disability | Disruption of PACS1-mediated protein trafficking affects synaptic and neuronal development | ClinVar, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Testis | 8.9 | Medium |
| Lung | 6.3 | Low |
| Liver | 4.1 | Low |
| Heart | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 10.2 | Neuronal model |
| HeLa (cervical carcinoma) | 7.5 | Epithelial |
| HEK293 (embryonic kidney) | 6.8 | Common expression model |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.607C>T (p.Arg203Trp) | Missense | Recurrent in Schuurs-Hoeijmakers syndrome | Gain-of-function? (altered sorting) |
| c.608G>A (p.Arg203Gln) | Missense | Rare | Likely pathogenic |
Mutation functional classification
Loss of Function (LOF)
Not established; no clear loss-of-function variants reported.
Gain of Function (GOF)
Proposed for p.Arg203Trp; may alter TGN localization of cargo proteins.
Dominant Negative (DN)
Possible mechanism for p.Arg203Trp, but not confirmed.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Protein sorting at the trans-Golgi network
• Endosome-to-TGN retrograde transport
Protein Summary
Phosphofurin acidic cluster sorting protein 1 (PACS1) is a 963-amino acid protein that localizes to the trans-Golgi network. It contains a furin-binding region and an acidic cluster-binding motif, enabling it to sort membrane proteins containing acidic clusters. PACS1 interacts with AP-1 and other coat proteins to regulate the subcellular distribution of cargo such as furin, mannose 6-phosphate receptor, and ion channels. The recurrent p.Arg203Trp mutation disrupts these interactions, leading to mislocalization of proteins and contributing to neurodevelopmental pathology.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PACS1 Knockout HEK293 Cell Line | EDJ-KQ14666 | Human | 55690 | Details Get a Quote |
| PACS1 Knockout A-549 Cell Line | EDJ-KQ44950 | Human | 55690 | Details Get a Quote |
| PACS1 Knockout HCT 116 Cell Line | EDJ-KQ44951 | Human | 55690 | Details Get a Quote |
| PACS1 Knockout HeLa Cell Line | EDJ-KQ44952 | Human | 55690 | Details Get a Quote |
