MANF (Mesencephalic Astrocyte Derived Neurotrophic Factor)
A neurotrophic factor with roles in endoplasmic reticulum stress response and neuroprotection.
Gene Information Card
| Symbol | MANF |
|---|---|
| Full Name | Mesencephalic Astrocyte Derived Neurotrophic Factor |
| Gene Type | Protein coding |
| Chromosomal Location | 3p21.2 |
| NCBI Gene ID | 7873 ncbi.nlm.nih.gov/gene/7873 |
| Ensembl ID | ENSG00000145050 |
| UniProt ID | P55145 |
| OMIM ID | 606464 |
| HGNC ID | 15461 |
| Aliases | ARMET, ARP |
Description
MANF (Mesencephalic Astrocyte Derived Neurotrophic Factor) is a protein-coding gene located on chromosome 3p21.2. It encodes a neurotrophic factor that is highly expressed in the brain and other tissues. MANF is involved in the unfolded protein response (UPR) and protects cells from endoplasmic reticulum (ER) stress-induced apoptosis. It has been implicated in neuroprotection, diabetes, and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Diabetes Mellitus, Type 2 | MANF variants may affect insulin secretion and beta-cell survival via ER stress modulation. | OMIM, ClinVar |
| Neurodegenerative Diseases (e.g., Parkinson's disease) | MANF exerts neuroprotective effects by reducing ER stress and promoting neuronal survival. | NCBI, UniProt |
| Cancer (e.g., breast, lung) | MANF expression is altered in various cancers; may influence tumor growth and metastasis through ER stress pathways. | COSMIC, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Salivary gland | 10.2 | Medium |
| Pancreas | 8.9 | Medium |
| Liver | 6.3 | Low |
| Kidney | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.3 | High expression |
| HeLa (cervical carcinoma) | 8.7 | Moderate expression |
| HEK293 (embryonic kidney) | 6.2 | Low expression |
| MCF7 (breast cancer) | 4.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.01% | Likely loss of function; may affect translation initiation |
| c.200C>T (p.Pro67Leu) | Missense | <0.01% | Unknown; reported in ClinVar |
| c.337G>A (p.Gly113Arg) | Missense | <0.01% | Unknown; reported in ClinVar |
Mutation functional classification
Loss of Function (LOF)
Mutations that disrupt the MANF protein structure or expression may impair its neuroprotective and ER stress-modulating functions.
Gain of Function (GOF)
No gain-of-function mutations have been characterized for MANF.
Dominant Negative (DN)
No dominant-negative mutations have been reported for MANF.
View complete mutation data：
Gene Ontology (GO)
| • endoplasmic reticulum unfolded protein response | • neurotrophin TRK receptor signaling pathway |
| • positive regulation of cell population proliferation | • negative regulation of apoptotic process |
| • protein binding |
Pathways
• Unfolded Protein Response (UPR)
• ER stress-induced apoptosis
Protein Summary
MANF is a 179-amino acid protein (UniProt P55145) that localizes to the endoplasmic reticulum and is secreted in response to ER stress. It contains an N-terminal saposin-like domain and a C-terminal ER retention signal. MANF binds to the KDEL receptor and modulates the UPR, protecting cells from apoptosis. It is also involved in neuroprotection and glucose homeostasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MANF Knockout HEK293 Cell Line | EDJ-KQ6137 | Human | 7873 | Details Get a Quote |
| MANF Knockout A-549 Cell Line | EDJ-KQ29918 | Human | 7873 | Details Get a Quote |
| MANF Knockout HCT 116 Cell Line | EDJ-KQ29919 | Human | 7873 | Details Get a Quote |
| MANF Knockout HeLa Cell Line | EDJ-KQ29920 | Human | 7873 | Details Get a Quote |
