SQSTM1 Gene (Sequestosome 1)
Key regulator of autophagy, NF-κB signaling, and oxidative stress response; implicated in Paget disease of bone, ALS, and cancer.
Gene Information Card
| Symbol | SQSTM1 |
|---|---|
| Full Name | Sequestosome 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 5q35.3 |
| NCBI Gene ID | 8878 ncbi.nlm.nih.gov/gene/8878 |
| Ensembl ID | ENSG00000161011 |
| UniProt ID | Q13501 |
| OMIM ID | 601530 |
| HGNC ID | 11280 |
| Aliases | p62, A170, OSIL, p60, ZIP3 |
Description
SQSTM1 encodes the sequestosome 1 protein (p62), a multifunctional adaptor protein that regulates autophagy, ubiquitin signaling, NF-κB activation, and oxidative stress responses. It acts as a cargo receptor for selective autophagy and interacts with key signaling molecules such as TRAF6, NRF2, and mTOR. Mutations in SQSTM1 are associated with Paget disease of bone, amyotrophic lateral sclerosis (ALS), frontotemporal dementia, and various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Paget disease of bone (PDB) | Loss-of-function or dominant-negative mutations impair autophagy and osteoclast regulation, leading to abnormal bone remodeling. | OMIM #167250; ClinVar |
| Amyotrophic lateral sclerosis (ALS) | Missense mutations (e.g., P392L) disrupt autophagy and protein aggregation clearance, contributing to motor neuron degeneration. | OMIM #616437; ClinVar |
| Frontotemporal dementia (FTD) | Similar mechanisms as ALS; SQSTM1 mutations impair TDP-43 and tau clearance. | OMIM #616437; ClinVar |
| Hepatocellular carcinoma | Altered p62 expression promotes NRF2 stabilization and mTOR activation, driving tumor growth. | COSMIC; NCBI PubMed |
| Breast cancer | SQSTM1 overexpression correlates with poor prognosis; p62 regulates NF-κB and autophagy in tumor progression. | COSMIC; NCBI PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Kidney | 10.2 | High |
| Brain | 8.1 | Medium |
| Heart | 6.4 | Medium |
| Skeletal muscle | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.8 | Cervical cancer cell line |
| HEK293 | 12.1 | Embryonic kidney cells |
| HepG2 | 14.3 | Hepatocellular carcinoma |
| SH-SY5Y | 9.7 | Neuroblastoma |
| MCF7 | 11.2 | Breast cancer |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| P392L | Missense | Common in PDB; ~20% of familial cases | Impairs ubiquitin binding and autophagy |
| G425R | Missense | Rare in ALS/FTD | Disrupts LC3 interaction, autophagy defect |
| A33V | Missense | Rare in ALS | Alters PB1 domain, oligomerization defect |
| L341V | Missense | Rare in PDB | Reduces TRAF6 binding, NF-κB dysregulation |
| R321C | Missense | Rare in ALS | Impairs UBA domain, ubiquitin binding loss |
Mutation functional classification
Loss of Function (LOF)
P392L, G425R, A33V, L341V, R321C – impair autophagy, ubiquitin binding, or protein interactions.
Gain of Function (GOF)
Not well established; some mutations may enhance NRF2 stabilization in cancer.
Dominant Negative (DN)
P392L in PDB acts dominant-negative by disrupting normal p62 function in osteoclasts.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Autophagy – selective autophagy (KEGG hsa04140)
• NF-κB signaling pathway (KEGG hsa04064)
• NRF2-ARE pathway (Reactome R-HSA-9759194)
• mTOR signaling (Reactome R-HSA-165159)
• Ubiquitin-proteasome pathway (Reactome R-HSA-983168)
Protein Summary
The SQSTM1 protein (p62) is a 440-amino acid scaffold with multiple domains: PB1 (oligomerization), ZZ-type zinc finger, TRAF6-binding, LC3-interacting region (LIR), Keap1-interacting region (KIR), and a C-terminal UBA domain. It serves as a hub for autophagy, ubiquitin signaling, and stress responses. p62 targets ubiquitinated cargo to autophagosomes, regulates NRF2 stability, and modulates NF-κB activation via TRAF6. Dysregulation of p62 contributes to bone disease, neurodegeneration, and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SQSTM1 Knockout HEK293 Cell Line | EDC08337 | Human | 8878 | Details Get a Quote |
| SQSTM1 Knockout A-549 Cell Line | EDJ-KQ46307 | Human | 8878 | Details Get a Quote |
| SQSTM1 Knockout HCT 116 Cell Line | EDJ-KQ46308 | Human | 8878 | Details Get a Quote |
| SQSTM1 Knockout HeLa Cell Line | EDC07625 | Human | 8878 | Details Get a Quote |
| SQSTM1 Knockout BEAS-2B Cell Line | EDJ-KZ491 | Human | 8878 | Details Get a Quote |
| SQSTM1 Knockout Hep-G2 Cell Line | EDJ-KZ492 | Human | 8878 | Details Get a Quote |
| Sqstm1 Knockout RAW 264.7 Cell Line | EDJ-KZ493 | Mouse | 18412 | Details Get a Quote |
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