SPG21

Protein identityUniProt · HPA

UniProt accession

Q9NZD8

Gene

SPG21

Ensembl

ENSG00000090487

Chromosome

15

Canonical length

308 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins

Subcellular location

Vesicles,Cytosol

OverviewNCBI Gene

The protein encoded by this gene binds to the hydrophobic C-terminal amino acids of CD4 which are involved in repression of T cell activation. The interaction with CD4 is mediated by the noncatalytic alpha/beta hydrolase fold domain of this protein. It is thus proposed that this gene product modulates the stimulatory activity of CD4. Mutations in this gene are associated with autosomal recessive spastic paraplegia 21 (SPG21), also known as mast syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2014]

Canonical amino-acid sequenceUniProt

308 residues, UniProt reviewed canonical sequence.

>Q9NZD8|SPG21
     1  MGEIKVSPDY NWFRGTVPLK KIIVDDDDSK IWSLYDAGPR SIRCPLIFLP PVSGTADVFF
    61  RQILALTGWG YRVIALQYPV YWDHLEFCDG FRKLLDHLQL DKVHLFGASL GGFLAQKFAE
   121  YTHKSPRVHS LILCNSFSDT SIFNQTWTAN SFWLMPAFML KKIVLGNFSS GPVDPMMADA
   181  IDFMVDRLES LGQSELASRL TLNCQNSYVE PHKIRDIPVT IMDVFDQSAL STEAKEEMYK
   241  LYPNARRAHL KTGGNFPYLC RSAEVNLYVQ IHLLQFHGTK YAAIDPSMVS AEELEVQKGS
   301  LGISQEEQ

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SPG21 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.23

Highest tissue expression

141 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SPG21.

Disease | AllUniProt

Conditions SPG21 is implicated in, by any mechanism.

• Spastic paraplegia 21, autosomal recessive (SPG21) MIM:248900

Disease | GeneticClinVar

13 pathogenic / likely-pathogenic of 204 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Mast syndrome
• Hereditary spastic paraplegia
• SPG21-related disorder
• Acute myeloid leukemia

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.83

gnomAD pLI

0

gnomAD missense Z

1.16

DepMap mean gene effect

-0.18

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• antigen receptor-mediated signaling pathway
• collateral sprouting
• epidermal growth factor receptor signaling pathway
• gene expression
• limb development
• locomotory behavior
• neuromuscular process
• neuron maturation
• response to epidermal growth factor

Molecular functions

• CD4 receptor binding

Cellular components

• cytosol
• endosome membrane
• Golgi apparatus
• trans-Golgi network transport vesicle

Protein domainsUniProt · Pfam · InterPro

• Alpha/beta hydrolase fold-1
• Alpha/Beta hydrolase fold
• alpha/beta hydrolase fold
• Maspardin

KeywordsUniProt

• Cytoplasm
• Endosome
• Golgi apparatus
• Hereditary spastic paraplegia
• Membrane
• Neurodegeneration
• Phosphoprotein

InteractionsUniProt · HPA

Protein binding partners of SPG21 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ALDH16A1
• CD4
• AKIRIN2
• ARL8A
• ATPAF2
• CTPS2
• DTX2
• PCNA
• RAB7A