SPG21 (Spastic Paraplegia 21, Maspardin)
Gene encoding maspardin, associated with autosomal recessive spastic paraplegia type 21 and potential roles in intracellular protein trafficking.
Gene Information Card
| Symbol | SPG21 |
|---|---|
| Full Name | SPG21, maspardin (mast syndrome, spastic paraplegia 21) |
| Gene Type | protein-coding |
| Chromosomal Location | 15q22.31 |
| NCBI Gene ID | 51324 ncbi.nlm.nih.gov/gene/51324 |
| Ensembl ID | ENSG00000137807 |
| UniProt ID | Q9NZD8 |
| OMIM ID | 608181 |
| HGNC ID | 20373 |
| Aliases | ACPMES, BM-019, GL010, maspardin, SPG21 |
Description
SPG21 encodes maspardin, a protein localized to endosomal/trans-Golgi compartments. It is involved in intracellular protein trafficking and lysosomal function. Loss-of-function mutations cause autosomal recessive spastic paraplegia 21 (SPG21), also known as mast syndrome (ACPMES), characterized by progressive spasticity, cognitive decline, and cerebellar ataxia.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Spastic paraplegia 21 (SPG21) / Mast syndrome (ACPMES) | Loss-of-function mutations in SPG21 impair maspardin function, disrupting endosomal trafficking and leading to neurodegeneration. | OMIM #248900; ClinVar; multiple case reports |
| Hereditary spastic paraplegia (broad) | SPG21 is a causative gene for autosomal recessive HSP, with evidence from linkage analysis and sequencing studies. | OMIM; NCBI GeneReviews |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebellum) | 12.5 | Medium |
| Brain (cortex) | 10.2 | Medium |
| Testis | 8.7 | Low |
| Heart | 6.3 | Low |
| Liver | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.3 | Neuronal model |
| HeLa (cervical carcinoma) | 8.9 | Epithelial |
| HEK293 (embryonic kidney) | 7.2 | Common expression system |
| U-87 MG (glioblastoma) | 11.0 | Glial model |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2T>C (p.Met1?) | Missense (start codon loss) | Rare | Loss of protein expression; pathogenic in SPG21 |
| c.175C>T (p.Arg59*) | Nonsense | Rare | Premature truncation; loss of function |
| c.335G>A (p.Trp112*) | Nonsense | Rare | Premature truncation; loss of function |
| c.404_405del (p.Gln135Argfs*10) | Frameshift | Rare | Frameshift leading to nonsense-mediated decay |
Mutation functional classification
Loss of Function (LOF)
Majority of reported SPG21 mutations are loss-of-function (nonsense, frameshift, start loss), leading to reduced or absent maspardin protein and impaired endosomal trafficking.
Gain of Function (GOF)
No evidence of gain-of-function mutations in SPG21.
Dominant Negative (DN)
No evidence of dominant-negative effects; inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • intracellular protein transport (GO:0006886) | • endosome (GO:0005768) |
| • Golgi apparatus (GO:0005794) | • protein binding (GO:0005515) |
| • membrane (GO:0016020) |
Pathways
• Endosomal trafficking (Reactome: R-HSA-5653656)
• Vesicle-mediated transport (Reactome: R-HSA-5653656)
Protein Summary
Maspardin (SPG21) is a 308-amino acid protein with a predicted transmembrane domain and a conserved domain of unknown function (DUF1081). It localizes to endosomes and the trans-Golgi network, where it participates in protein sorting and trafficking. Loss of maspardin function leads to accumulation of autophagic vesicles and neurodegeneration, particularly in the corticospinal tracts and cerebellum.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SPG21 Knockout HEK293 Cell Line | EDJ-KQ11051 | Human | 51324 | Details Get a Quote |
| SPG21 Knockout A-549 Cell Line | EDJ-KQ38970 | Human | 51324 | Details Get a Quote |
| SPG21 Knockout HCT 116 Cell Line | EDJ-KQ38971 | Human | 51324 | Details Get a Quote |
| SPG21 Knockout HeLa Cell Line | EDJ-KQ38972 | Human | 51324 | Details Get a Quote |
