SMCR8 Gene
SMCR8: A Key Regulator in Autophagy and Neurodegeneration
Gene Information Card
| Symbol | SMCR8 |
|---|---|
| Full Name | SMCR8-C9orf72 Complex Subunit |
| Gene Type | Protein coding |
| Chromosomal Location | 17p11.2 |
| NCBI Gene ID | 140775 ncbi.nlm.nih.gov/gene/140775 |
| Ensembl ID | ENSG00000176994 |
| UniProt ID | Q8TEV9 |
| OMIM ID | 616932 |
| HGNC ID | 26521 |
| Aliases | ALS2CR8, C17orf32, FLJ32642 |
Description
The SMCR8 gene encodes a protein that forms a complex with C9orf72 and WDR41, acting as a guanine nucleotide exchange factor (GEF) for Rab GTPases, particularly Rab8a and Rab39a. This complex is essential for the initiation of autophagy and lysosomal biogenesis. Mutations in SMCR8 are associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), highlighting its role in neurodegenerative diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Amyotrophic Lateral Sclerosis (ALS) | Loss of SMCR8 function disrupts autophagy and lysosomal trafficking, leading to accumulation of protein aggregates and neuronal death. | ClinVar, OMIM |
| Frontotemporal Dementia (FTD) | Impaired SMCR8-mediated autophagy contributes to TDP-43 pathology and neurodegeneration. | ClinVar, OMIM |
| Smith-Magenis Syndrome (SMS) | SMCR8 is located in the SMS critical region on chromosome 17p11.2; haploinsufficiency may contribute to the phenotype. | OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 15.2 | Medium |
| Spinal Cord | 12.8 | Medium |
| Lung | 8.5 | Low |
| Liver | 6.1 | Low |
| Kidney | 7.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 18.4 | High expression; relevant for neuronal studies |
| HeLa (cervical carcinoma) | 9.2 | Moderate expression |
| HEK293 (embryonic kidney) | 7.8 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.118C>T (p.Arg40*) | Nonsense | Rare | Loss of function; associated with ALS |
| c.307G>A (p.Gly103Arg) | Missense | Rare | Impaired autophagy; reported in FTD |
| c.502_503del (p.Leu168Valfs*12) | Frameshift | Rare | Loss of function; linked to ALS |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations in SMCR8 lead to truncated or absent protein, disrupting the C9orf72-SMCR8-WDR41 complex and impairing autophagy, contributing to ALS and FTD.
Gain of Function (GOF)
No evidence of gain-of-function mutations in SMCR8.
Dominant Negative (DN)
No evidence of dominant-negative mutations in SMCR8.
View complete mutation data：
Gene Ontology (GO)
| • autophagy | • GTPase activator activity |
| • lysosomal transport | • protein localization to lysosome |
| • Rab GTPase binding | • regulation of autophagosome assembly |
Pathways
• Autophagy (KEGG hsa04140)
• Lysosome (KEGG hsa04142)
• C9orf72-SMCR8-WDR41 complex pathway
Protein Summary
The SMCR8 protein (UniProt Q8TEV9) is a 444-amino acid protein that functions as a subunit of the C9orf72-SMCR8-WDR41 complex. It acts as a guanine nucleotide exchange factor (GEF) for Rab8a and Rab39a, regulating autophagy and lysosomal biogenesis. The protein is widely expressed, with highest levels in the brain and spinal cord. Mutations in SMCR8 are linked to ALS and FTD, underscoring its critical role in neuronal homeostasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SMCR8 Knockout HEK293 Cell Line | EDJ-KQ9812 | Human | 140775 | Details Get a Quote |
| SMCR8 Knockout A-549 Cell Line | EDJ-KQ36661 | Human | 140775 | Details Get a Quote |
| SMCR8 Knockout HCT 116 Cell Line | EDJ-KQ36662 | Human | 140775 | Details Get a Quote |
| SMCR8 Knockout HeLa Cell Line | EDJ-KQ36663 | Human | 140775 | Details Get a Quote |
| SMCR8 Knockout HAP1 Cell Line | EDC08074 | Human | 140775 | Details Get a Quote |
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