SPG21

Chr 15AR

SPG21 abhydrolase domain containing, maspardin

Also known as: ABHD21, ACP33, BM-019, GL010, MAST

NCBI Gene: 51324ENSG00000090487UniProt: Q9NZD8

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]

Primary Disease Associations & Inheritance

Mast syndromeMIM #248900
AR
Mast syndromeMIM #248900
AR
UniProtSpastic paraplegia 21, autosomal recessive
224
ClinVar variants
24
Pathogenic / LP
—
pLI score
0
Active trials
Clinical Summary— SPG21
📋
ClinVar Variants
24 Pathogenic / Likely Pathogenic· 84 VUS of 224 total submissions
Some data sources returned errors (1)

gnomad: Error: gnomAD API error: 502

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

ClinVar Variant Classifications

224 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic10
VUS84
Likely Benign59
Benign25
Conflicting13
14
Pathogenic
10
Likely Pathogenic
84
VUS
59
Likely Benign
25
Benign
13
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
1
9
0
14
Likely Pathogenic
4
0
6
0
10
VUS
1
52
28
3
84
Likely Benign
0
0
32
27
59
Benign
0
0
25
0
25
Conflicting
—13
Total95310030205

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SPG21 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

3 OMIM entries

OMIM
MAST SYNDROME; MASTS
MIM #248900 · #

Mast syndrome

MIM #248900

Molecular basis of disorder known

Autosomal recessive

Mast syndrome

MIM #248900

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
ALS5/SPG11/KIAA1840 mutations cause autosomal recessive axonal Charcot-Marie-Tooth disease.
Montecchiani C et al.·Brain
2016
Hereditary spastic paraplegias with autosomal dominant, recessive, X-linked, or maternal trait of inheritance.
Finsterer J et al.·J Neurol Sci
2012Review
Overlapping phenotypes in complex spastic paraplegias SPG11, SPG15, SPG35 and SPG48.
Pensato V et al.·Brain
2014
Cognitive impairment in hereditary spastic paraparesis: An overlooked aspect of a motor disorder.
Falcone GMI et al.·Neurol Sci
2026
Molecular epidemiology and clinical spectrum of hereditary spastic paraplegia in the Japanese population based on comprehensive mutational analyses.
Ishiura H et al.·J Hum Genet
2014
Complicated hereditary spastic paraplegia with thin corpus callosum (HSP-TCC) and childhood onset.
Brockmann K et al.·Neuropediatrics
2005Case report
Hereditary spastic paraplegia with thin corpus callosum: reduction of the SPG11 interval and evidence for further genetic heterogeneity.
Lossos A et al.·Arch Neurol
2006
Refinement of the SPG15 candidate interval and phenotypic heterogeneity in three large Arab families.
Elleuch N et al.·Neurogenetics
2007Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Maspardin/SPG21 controls lysosome motility and TFEB phosphorylation through RAB7 positioning.
Jacqmin T et al.·J Cell Biol
2026🔓 Open Access
The hereditary spastic paraplegia type 21 (SPG21) protein is a RAB7A effector that promotes noncanonical mTORC1-catalyzed TFEB phosphorylation and cytoplasmic retention.
Kunselman JM et al.·Mol Biol Cell
2025
SPG21, a potential oncogene targeted by miR-128-3p, amplifies HBx-induced carcinogenesis and chemoresistance via activation of TRPM7-mediated JNK pathway in hepatocellular carcinoma.
Zhou P et al.·Cell Oncol (Dordr)
2024
Mast Syndrome Outside the Amish Community: SPG21 in Europe.
Amprosi M et al.·Front Neurol
2021🔓 Open Access
Identification of a large homozygous SPG21 deletion in a Chinese patient with Mast syndrome.
Xue YY et al.·CNS Neurosci Ther
2021🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools