PPP1R15B
Protein Phosphatase 1 Regulatory Subunit 15B
Gene Information Card
| Symbol | PPP1R15B |
|---|---|
| Full Name | Protein Phosphatase 1 Regulatory Subunit 15B |
| Gene Type | protein-coding |
| Chromosomal Location | 1q32.1 |
| NCBI Gene ID | 84919 ncbi.nlm.nih.gov/gene/84919 |
| Ensembl ID | ENSG00000143178 |
| UniProt ID | Q5SW96 |
| OMIM ID | 613257 |
| HGNC ID | 14951 |
| Aliases | GADD34, GADD34B, MGC110993 |
Description
PPP1R15B encodes a regulatory subunit of protein phosphatase 1 (PP1). It functions as a stress-inducible protein that recruits PP1 to dephosphorylate eukaryotic translation initiation factor 2 alpha (eIF2α), thereby attenuating the integrated stress response and restoring protein synthesis. The gene is involved in cellular stress recovery and has been implicated in various cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Microcephaly, short stature, and impaired glucose metabolism | Loss-of-function mutations in PPP1R15B disrupt eIF2α dephosphorylation, leading to chronic integrated stress response activation and impaired cell growth. | OMIM #613257; ClinVar |
| Cancer (various) | Overexpression of PPP1R15B (GADD34) in tumors promotes stress resistance and survival by restoring translation under oncogenic stress. | COSMIC; NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 8.5 | Medium |
| Liver | 6.2 | Medium |
| Kidney | 5.1 | Low |
| Heart | 4.3 | Low |
| Testis | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 12.0 | High expression |
| HeLa | 9.5 | Medium expression |
| HepG2 | 7.8 | Medium expression |
| K562 | 4.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1015C>T (p.Arg339Ter) | Nonsense | <0.01% | Loss of function; associated with microcephaly and growth retardation |
| c.1462G>A (p.Glu488Lys) | Missense | <0.01% | Loss of function; impaired PP1 binding |
| c.1742_1743del (p.Leu581Argfs*12) | Frameshift | <0.01% | Loss of function; truncated protein |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations impair eIF2α dephosphorylation, leading to persistent integrated stress response and cellular growth defects.
Gain of Function (GOF)
Gain-of-function (overexpression) in cancer cells enhances eIF2α dephosphorylation, promoting survival under stress.
Dominant Negative (DN)
No dominant-negative mutations reported in PPP1R15B.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Integrated stress response (ISR) - eIF2α dephosphorylation
• Unfolded protein response (UPR) - recovery phase
• PP1 regulatory network
Protein Summary
PPP1R15B (GADD34) is a 674-amino acid protein that acts as a stress-inducible regulatory subunit of protein phosphatase 1 (PP1). It recruits PP1 to dephosphorylate eIF2α, thereby terminating the integrated stress response and allowing resumption of protein synthesis. The protein contains an N-terminal domain involved in stress granule localization and a C-terminal PP1-binding motif. It is widely expressed, with highest levels in brain and liver. Mutations cause microcephaly, short stature, and glucose metabolism defects, while overexpression is observed in several cancers.
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