X-linked complicated spastic paraplegia type 1

Summary

X-linked complicated spastic paraplegia type 1 (MONDO:0017630) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• Phenotypes (HPO): 9

Clinical features

Signs & symptoms

Clinical features (HPO)

9 HPO clinical features (Orphanet curated; top 9 by frequency):

HPO ID	Term	Frequency
HP:0001258	Spastic paraplegia	Very frequent (80-99%)
HP:0001256	Intellectual disability, mild	Frequent (30-79%)
HP:0002342	Intellectual disability, moderate	Frequent (30-79%)
HP:0002493	Upper motor neuron dysfunction	Frequent (30-79%)
HP:0007340	Lower limb muscle weakness	Frequent (30-79%)
HP:0100543	Cognitive impairment	Frequent (30-79%)
HP:0001181	Adducted thumb	Occasional (5-29%)
HP:0001251	Ataxia	Occasional (5-29%)
HP:0001268	Mental deterioration	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	X-linked complicated spastic paraplegia type 1
Mondo ID	MONDO:0017630
Orphanet	306617
UMLS	C5779711
MedGen	1843445
GARD	0012525
Is cancer (heuristic)	no

Also known as: SPG1

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › disorder of development or morphogenesis › L1 syndrome › X-linked complicated spastic paraplegia type 1

Related subtypes (3): MASA syndrome, X-linked complicated corpus callosum dysgenesis, X-linked hydrocephalus with stenosis of the aqueduct of Sylvius

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
L1CAM	Definitive	X-linked	X-linked hydrocephalus with stenosis of the aqueduct of Sylvius	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
L1CAM	Orphanet:1497	X-linked complicated corpus callosum dysgenesis
L1CAM	Orphanet:2182	Hydrocephalus with stenosis of the aqueduct of Sylvius
L1CAM	Orphanet:2466	MASA syndrome
L1CAM	Orphanet:306617	X-linked complicated spastic paraplegia type 1

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
L1CAM	HGNC:6470	ENSG00000198910	P32004	Neural cell adhesion molecule L1	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
L1CAM	Neural cell adhesion molecule L1	Neural cell adhesion molecule involved in the dynamics of cell adhesion and in the generation of transmembrane signals at tyrosine kinase receptors.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
L1CAM	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cerebellar hemisphere	1
cortical plate	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
L1CAM	239	ubiquitous	marker	cortical plate, right hemisphere of cerebellum, cerebellar hemisphere

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
L1CAM	2,937

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
L1CAM	P32004	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Signal transduction by L1	1	519.1×	0.009	L1CAM
Basigin interactions	1	439.2×	0.009	L1CAM
Interaction between L1 and Ankyrins	1	368.4×	0.009	L1CAM
Recycling pathway of L1	1	223.9×	0.011	L1CAM
L1CAM interactions	1	120.2×	0.017	L1CAM
Cell surface interactions at the vascular wall	1	95.2×	0.018	L1CAM
Axon guidance	1	45.1×	0.029	L1CAM
Nervous system development	1	42.9×	0.029	L1CAM
Hemostasis	1	36.0×	0.031	L1CAM
Developmental Biology	1	14.5×	0.069	L1CAM

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of axon extension	1	510.7×	0.012	L1CAM
axon development	1	455.5×	0.012	L1CAM
synapse organization	1	280.9×	0.013	L1CAM
cell-matrix adhesion	1	163.6×	0.013	L1CAM
homophilic cell-cell adhesion	1	140.4×	0.013	L1CAM
chemotaxis	1	135.9×	0.013	L1CAM
neuron projection development	1	122.1×	0.013	L1CAM
axon guidance	1	90.6×	0.015	L1CAM
cell migration	1	61.5×	0.020	L1CAM
nervous system development	1	45.9×	0.024	L1CAM
cell adhesion	1	37.5×	0.027	L1CAM

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
L1CAM	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
L1CAM	2	Binding:2

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	L1CAM
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
L1CAM	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.