SPG11

SPG11 vesicle trafficking associated, spatacsin

5 disorders 3 causative 2 untyped 15q21.1 gene with protein product

HGNC:11226 Monarch NCBI Gene 80208 ENSG00000104133 UniProt Q96JI7 OMIM 610844

Previous symbols: KIAA1840, ALS5. Aliases: FLJ21439.

Normal function · from ai-gene-review (Q96JI7, commit 79fe13b38970) · AI-generated, not KB evidence

SPG11 encodes spatacsin, a large cytoplasmic/peripheral membrane-associated protein that functions with SPG15/spastizin and AP-5 in endolysosomal membrane remodeling. The strongest protein-homeostasis evidence supports a core role in autophagic lysosome reformation, lysosomal tubulation, lysosome membrane recycling, and ER-linked lysosome trafficking/organization. SPG11 also has supported neuronal axonal/synaptic transport contexts, but its principal described cellular role is endolysosomal membrane remodeling.

AP5-SPG11-SPG15-dependent organization and remodeling of late endosomal/lysosomal membranes during autophagic lysosome reformation, lysosomal tubulation, and lysosome membrane recycling.

directly involved in: lysosome organization; lysosomal membrane organization; membrane bending · locations: endoplasmic reticulum; late endosome; lysosome; lysosomal membrane; cytosol

In the knowledge base · computed from kb/ at build time

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

Disorder	Relationship	Where the gene appears
Charcot-Marie-Tooth Disease Type 2	causative	mechanism: Impaired Autophagy-Lysosome Function subtype: CMT2X scoped to subtype: CMT2X
Hereditary Spastic Paraplegia 11	causative	mechanism: Spatacsin Loss of Function
Juvenile Amyotrophic Lateral Sclerosis	causative loss of function	mechanism: Spatacsin Loss of Function and Lysosomal-Autophagic Dysfunction subtype: ALS5 scoped to subtype: ALS5
Complex Hereditary Spastic Paraplegia	untyped	mechanism: Pleiotropic SPG-Protein Dysfunction Beyond the Corticospinal Tract subtype: AR Complex HSP scoped to subtype: AR Complex HSP
Hereditary Spastic Paraplegia	untyped	subtype: SPG11 scoped to subtype: SPG11

ClinGen gene–disease validity · snapshot 2026-10-03 · matched to entries by MONDO

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

ClinGen disease	MOI	Classification	dismech entry
hereditary spastic paraplegia 11 MONDO:0011445	AR	Definitive 2023-06-07	Hereditary Spastic Paraplegia 11 causative

Mechanism modules · computed from kb/

corticospinal_tract_axonopathy via Hereditary Spastic Paraplegia 11

Identity from HGNC (snapshot 2026-10-01). Page layers are described in the gene pages documentation.