Hereditary spastic paraplegia 13

Summary

Hereditary spastic paraplegia 13 (MONDO:0011532) is a disease caused by HSPD1 (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: HSPD1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 50
• Phenotypes (HPO): 16

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		10	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

16 HPO clinical features (Orphanet curated; top 16 by frequency):

HPO ID	Term	Frequency
HP:0001258	Spastic paraplegia	Very frequent (80-99%)
HP:0002839	Urinary bladder sphincter dysfunction	Very frequent (80-99%)
HP:0000020	Urinary incontinence	Frequent (30-79%)
HP:0001347	Hyperreflexia	Frequent (30-79%)
HP:0002061	Lower limb spasticity	Frequent (30-79%)
HP:0002064	Spastic gait	Frequent (30-79%)
HP:0002166	Impaired vibration sensation in the lower limbs	Frequent (30-79%)
HP:0003487	Babinski sign	Frequent (30-79%)
HP:0007256	Abnormal pyramidal sign	Frequent (30-79%)
HP:0007340	Lower limb muscle weakness	Frequent (30-79%)
HP:0007350	Hyperreflexia in upper limbs	Frequent (30-79%)
HP:0000012	Urinary urgency	Occasional (5-29%)
HP:0001761	Pes cavus	Occasional (5-29%)
HP:0002650	Scoliosis	Occasional (5-29%)
HP:0000365	Hearing impairment	Very rare (<1-4%)
HP:0000510	Rod-cone dystrophy	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	hereditary spastic paraplegia 13
Mondo ID	MONDO:0011532
MeSH	C537485
OMIM	605280
Orphanet	100994
DOID	DOID:0110766
UMLS	C1854467
MedGen	344289
GARD	0009616
Is cancer (heuristic)	no

Also known as: hereditary spastic paraplegia caused by mutation in HSPD1 · hereditary spastic paraplegia type 13 · HSPD1 hereditary spastic paraplegia · spastic paraplegia 13 · spastic paraplegia 13, autosomal dominant · SPG13

Data availability: 50 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › palsy › paraplegia › hereditary spastic paraplegia › hereditary spastic paraplegia 13

Related subtypes (44): hereditary spastic paraplegia 3A, hereditary spastic paraplegia 4, mast syndrome, hereditary spastic paraplegia 5A, hereditary spastic paraplegia 16, hereditary spastic paraplegia 2, macrocephaly-spastic paraplegia-dysmorphism syndrome, Charcot-Marie-Tooth disease type 5, hereditary spastic paraplegia 6, hereditary spastic paraplegia 10, hereditary spastic paraplegia 14, hereditary spastic paraplegia 7, hereditary spastic paraplegia 33, hereditary spastic paraplegia 31, hereditary spastic paraplegia 30, hereditary spastic paraplegia 35, hereditary spastic paraplegia 50, hereditary spastic paraplegia 48, hereditary spastic paraplegia 51, hereditary spastic paraplegia 47, hereditary spastic paraplegia 52, hereditary spastic paraplegia 56, early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome, hereditary spastic paraplegia 77, pure hereditary spastic paraplegia, complex hereditary spastic paraplegia, pure or complex hereditary spastic paraplegia, spastic paraplegia 87, autosomal recessive, spastic paraplegia 80, autosomal dominant, spastic paraplegia 81, autosomal recessive, spastic paraplegia 82, autosomal recessive, spastic paraplegia 83, autosomal recessive, spastic paraplegia 88, autosomal dominant, spastic paraplegia 79A, autosomal dominant, with ataxia, spastic paraplegia 89, autosomal recessive, spastic paraplegia 90A, autosomal dominant, spastic paraplegia 90B, autosomal recessive, spastic paraplegia 91, autosomal dominant, with or without cerebellar ataxia, spastic paraplegia 72b, autosomal recessive, spastic paraplegia 92, autosomal recessive, spastic paraplegia 93, autosomal recessive, IFIH1-related hereditary spastic paraplegia, RNASEH2B-related hereditary spastic paraplegia, ADAR-related hereditary spastic paraplegia

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

ClinVar germline variants

50 retrieved; paginated sample, class counts are floors:

24 uncertain significance, 12 benign, 7 conflicting classifications of pathogenicity, 4 benign/likely benign, 2 pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
17557	NM_002156.5(HSPD1):c.292G>A (p.Val98Ile)	HSPD1	Pathogenic	criteria provided, single submitter
561192	NM_002156.5(HSPD1):c.1381C>G (p.Gln461Glu)	HSPD1	Pathogenic	no assertion criteria provided
129242	NM_002156.5(HSPD1):c.27C>G (p.Arg9=)	HSPD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
188178	NM_002156.5(HSPD1):c.794A>G (p.Asn265Ser)	HSPD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
216941	NM_002156.5(HSPD1):c.1607C>T (p.Ala536Val)	HSPD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
333308	NM_002156.5(HSPD1):c.869+12T>C	HSPD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
333312	NM_002156.5(HSPD1):c.428-15A>G	HSPD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
895766	NM_002156.5(HSPD1):c.175-8T>C	HSPD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
897576	NM_002156.5(HSPD1):c.1029A>G (p.Gly343=)	HSPD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1440407	NM_002156.5(HSPD1):c.445G>C (p.Asp149His)	HSPD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2530675	NM_002156.5(HSPD1):c.205G>A (p.Gly69Arg)	HSPD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2693833	NM_002156.5(HSPD1):c.1462T>A (p.Ser488Thr)	HSPD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
333301	NM_002156.5(HSPD1):c.*454T>G	HSPD1	Uncertain significance	criteria provided, single submitter
333302	NM_002156.5(HSPD1):c.*384T>A	HSPD1	Uncertain significance	criteria provided, single submitter
333303	NM_002156.5(HSPD1):c.*313A>G	HSPD1	Uncertain significance	criteria provided, single submitter
333304	NM_002156.5(HSPD1):c.*56G>A	HSPD1	Uncertain significance	criteria provided, single submitter
333307	NM_002156.5(HSPD1):c.1207G>A (p.Val403Met)	HSPD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
333309	NM_002156.5(HSPD1):c.859G>A (p.Val287Ile)	HSPD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
333310	NM_002156.5(HSPD1):c.607-4A>G	HSPD1	Uncertain significance	criteria provided, single submitter
333311	NM_002156.5(HSPD1):c.429T>C (p.Gly143=)	HSPD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3585124	NM_002156.5(HSPD1):c.299A>T (p.Asp100Val)	HSPD1	Uncertain significance	criteria provided, single submitter
3777136	NM_002156.5(HSPD1):c.392T>G (p.Ile131Ser)	HSPD1	Uncertain significance	criteria provided, single submitter
4086208	NM_002156.5(HSPD1):c.1705_1716dup (p.Met572_Phe573insGlyGlyGlyMet)	HSPD1	Uncertain significance	criteria provided, single submitter
4279831	NM_002156.5(HSPD1):c.1169T>C (p.Leu390Pro)	HSPD1	Uncertain significance	criteria provided, single submitter
631513	NM_002156.5(HSPD1):c.870-3C>T	HSPD1	Uncertain significance	no assertion criteria provided
895688	NM_002156.5(HSPD1):c.*459T>G	HSPD1	Uncertain significance	criteria provided, single submitter
895767	NM_002156.5(HSPD1):c.145G>C (p.Asp49His)	HSPD1	Uncertain significance	criteria provided, single submitter
895969	NM_002156.5(HSPD1):c.*121T>C	HSPD1	Uncertain significance	criteria provided, single submitter
895971	NM_002156.5(HSPD1):c.1388T>C (p.Ile463Thr)	HSPD1	Uncertain significance	criteria provided, single submitter
898732	NM_002156.5(HSPD1):c.662G>A (p.Arg221Gln)	HSPD1	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 2 · 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
HSPD1	Strong	Autosomal dominant	hereditary spastic paraplegia 13	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HSPD1	Orphanet:100994	Autosomal dominant spastic paraplegia type 13
HSPD1	Orphanet:280288	Pelizaeus-Merzbacher-like disease due to HSPD1 mutation

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
HSPD1	HGNC:5261	ENSG00000144381	P10809	60 kDa heat shock protein, mitochondrial	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HSPD1	60 kDa heat shock protein, mitochondrial	Chaperonin implicated in mitochondrial protein import and macromolecular assembly.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HSPD1	Other/Unknown	no		Cpn60/GroEL, Cpn60/GroEL/TCP-1, Chaperonin_Cpn60_CS

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
adrenal tissue	1
right adrenal gland	1
right adrenal gland cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HSPD1	217	ubiquitous	marker	adrenal tissue, right adrenal gland, right adrenal gland cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HSPD1	7,876

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HSPD1	P10809	31

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
TFAP2A acts as a transcriptional repressor during retinoic acid induced cell differentiation	1	2284.0×	0.002	HSPD1
Mitochondrial unfolded protein response (UPRmt)	1	601.0×	0.003	HSPD1
Mitochondrial protein import	1	167.9×	0.008	HSPD1
Mitochondrial protein degradation	1	114.2×	0.009	HSPD1

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
isotype switching to IgG isotypes	1	16852.0×	0.002	HSPD1
mitochondrial unfolded protein response	1	8426.0×	0.002	HSPD1
protein import into mitochondrial intermembrane space	1	5617.3×	0.002	HSPD1
‘de novo’ protein folding	1	4213.0×	0.002	HSPD1
biological process involved in interaction with symbiont	1	2808.7×	0.002	HSPD1
positive regulation of T cell mediated immune response to tumor cell	1	2407.4×	0.002	HSPD1
negative regulation of execution phase of apoptosis	1	2407.4×	0.002	HSPD1
cellular response to interleukin-7	1	1296.3×	0.003	HSPD1
MyD88-dependent toll-like receptor signaling pathway	1	936.2×	0.003	HSPD1
apoptotic mitochondrial changes	1	887.0×	0.003	HSPD1
positive regulation of macrophage activation	1	842.6×	0.003	HSPD1
positive regulation of execution phase of apoptosis	1	842.6×	0.003	HSPD1
chaperone-mediated protein complex assembly	1	702.2×	0.003	HSPD1
positive regulation of interferon-alpha production	1	648.1×	0.003	HSPD1
protein refolding	1	624.1×	0.003	HSPD1
response to cold	1	561.7×	0.003	HSPD1
B cell proliferation	1	481.5×	0.003	HSPD1
B cell activation	1	455.5×	0.003	HSPD1
positive regulation of T cell activation	1	443.5×	0.003	HSPD1
positive regulation of interleukin-10 production	1	401.2×	0.004	HSPD1
positive regulation of interleukin-12 production	1	391.9×	0.004	HSPD1
response to unfolded protein	1	300.9×	0.004	HSPD1
T cell activation	1	259.3×	0.005	HSPD1
positive regulation of type II interferon production	1	224.7×	0.005	HSPD1
positive regulation of interleukin-6 production	1	166.8×	0.007	HSPD1
protein maturation	1	163.6×	0.007	HSPD1
protein folding	1	103.4×	0.010	HSPD1
protein stabilization	1	66.9×	0.015	HSPD1
negative regulation of apoptotic process	1	34.8×	0.029	HSPD1

Therapeutics

Drug target analysis

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

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

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
HSPD1	CHOLECALCIFEROL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HSPD1	27	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CHOLECALCIFEROL	4	HSPD1
EVANS BLUE	4	HSPD1
PHENOXYBENZAMINE HYDROCHLORIDE	4	HSPD1
ADAPALENE	4	HSPD1
ERGOCALCIFEROL	4	HSPD1
METABROMSALAN	4	HSPD1
BITHIONOL	4	HSPD1
TRETINOIN	4	HSPD1
BENZBROMARONE	4	HSPD1
RIBOFLAVIN 5’-PHOSPHATE SODIUM	4	HSPD1
ETHACRYNIC ACID	4	HSPD1
HEXACHLOROPHENE	4	HSPD1
TANNIC ACID	4	HSPD1
MENADIONE	4	HSPD1
IVERMECTIN	4	HSPD1
GENTIAN VIOLET	4	HSPD1
MESALAMINE	4	HSPD1
CURCUMIN	3	HSPD1
CETYLPYRIDINIUM CHLORIDE	3	HSPD1
SURAMIN	3	HSPD1
EPIGALOCATECHIN GALLATE	3	HSPD1
CLOSANTEL	2	HSPD1
LAPACHONE	2	HSPD1
BENZETHONIUM CHLORIDE	2	HSPD1
RAFOXANIDE	2	HSPD1
DICHLOROPHEN	2	HSPD1
PLUMBAGIN	1	HSPD1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
HSPD1	22	Binding:18, ADMET:2, Functional: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

27 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.

Compound	Max phase	Cohort target (bioactivity)
CHOLECALCIFEROL	4	HSPD1
EVANS BLUE	4	HSPD1
PHENOXYBENZAMINE HYDROCHLORIDE	4	HSPD1
ADAPALENE	4	HSPD1
ERGOCALCIFEROL	4	HSPD1
METABROMSALAN	4	HSPD1
BITHIONOL	4	HSPD1
TRETINOIN	4	HSPD1
BENZBROMARONE	4	HSPD1
RIBOFLAVIN 5’-PHOSPHATE SODIUM	4	HSPD1
ETHACRYNIC ACID	4	HSPD1
HEXACHLOROPHENE	4	HSPD1
TANNIC ACID	4	HSPD1
MENADIONE	4	HSPD1
IVERMECTIN	4	HSPD1
GENTIAN VIOLET	4	HSPD1
MESALAMINE	4	HSPD1
CURCUMIN	3	HSPD1
CETYLPYRIDINIUM CHLORIDE	3	HSPD1
SURAMIN	3	HSPD1
EPIGALOCATECHIN GALLATE	3	HSPD1
CLOSANTEL	2	HSPD1
LAPACHONE	2	HSPD1
BENZETHONIUM CHLORIDE	2	HSPD1
RAFOXANIDE	2	HSPD1
DICHLOROPHEN	2	HSPD1
PLUMBAGIN	1	HSPD1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	HSPD1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.