Supranuclear palsy, progressive, 1

disease

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Also known as classic progressive supranuclear palsy syndromeclassic PSP syndromePSNP1PSPRichardson syndromeSteele-Richardson-Olszewski diseaseSteele-Richardson-Olszewski syndromesupranuclear palsy, progressivesupranuclear palsy, progressive, type 1

Summary

Supranuclear palsy, progressive, 1 (MONDO:0010997) is a disease caused by MAPT (GenCC Strong), with 1 cohort gene and 17 clinical trials. Top therapeutic interventions include donepezil and gosuranemab.

At a glance

Prevalence: 1-9 / 100 000 (Europe)
Causal gene: MAPT (GenCC Strong)
Cohort genes: 1
ClinVar variants: 17
Phenotypes (HPO): 28
Clinical trials: 17

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000		Europe	Not yet validated

Signs & symptoms

Clinical features (HPO)

28 HPO clinical features (Orphanet curated; top 28 by frequency):

HPO ID	Term	Frequency
HP:0002172	Postural instability	Very frequent (80-99%)
HP:0002527	Falls	Very frequent (80-99%)
HP:0001268	Mental deterioration	Very frequent (80-99%)
HP:0000514	Slow saccadic eye movements	Frequent (30-79%)
HP:0030953	Conjunctival hyperemia	Frequent (30-79%)
HP:0000633	Decreased lacrimation	Frequent (30-79%)
HP:0000622	Blurred vision	Frequent (30-79%)
HP:0000643	Blepharospasm	Frequent (30-79%)
HP:0000613	Photophobia	Frequent (30-79%)
HP:0100710	Impulsivity	Frequent (30-79%)
HP:0007164	Slowed slurred speech	Frequent (30-79%)
HP:0000605	Supranuclear gaze palsy	Frequent (30-79%)
HP:0001300	Parkinsonism	Frequent (30-79%)
HP:0002067	Bradykinesia	Frequent (30-79%)
HP:0002141	Gait imbalance	Frequent (30-79%)
HP:0000511	Vertical supranuclear gaze palsy	Frequent (30-79%)
HP:0002530	Axial dystonia	Frequent (30-79%)
HP:0001260	Dysarthria	Frequent (30-79%)
HP:0007158	Progressive extrapyramidal muscular rigidity	Frequent (30-79%)
HP:0000570	Abnormal saccadic eye movements	Frequent (30-79%)
HP:0007086	Social and occupational deterioration	Occasional (5-29%)
HP:0002068	Neuromuscular dysphagia	Occasional (5-29%)
HP:0006921	Axial muscle stiffness	Occasional (5-29%)
HP:0002304	Akinesia	Occasional (5-29%)
HP:0001337	Tremor	Occasional (5-29%)
HP:0001332	Dystonia	Occasional (5-29%)
HP:0007256	Abnormal pyramidal sign	Occasional (5-29%)
HP:0002548	Parkinsonism with favorable response to dopaminergic medication	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	supranuclear palsy, progressive, 1
Mondo ID	MONDO:0010997
OMIM	601104
Orphanet	240071
UMLS	C4551863
MedGen	1640811
GARD	0017182
Is cancer (heuristic)	no

Also known as: classic progressive supranuclear palsy syndrome · classic PSP syndrome · PSNP1 · PSP · Richardson syndrome · Steele-Richardson-Olszewski disease · Steele-Richardson-Olszewski syndrome · supranuclear palsy, progressive · supranuclear palsy, progressive, 1 · supranuclear palsy, progressive, type 1

Data availability: 17 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › progressive supranuclear palsy › supranuclear palsy, progressive, 1

Related subtypes (3): supranuclear palsy, progressive, 2, supranuclear palsy, progressive, 3, atypical progressive supranuclear palsy syndrome

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

17 retrieved; paginated sample, class counts are floors:

7 uncertain significance, 5 pathogenic, 2 benign/likely benign, 1 likely benign, 1 benign, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
14245	NM_001377265.1(MAPT):c.2078C>T (p.Pro693Leu)	MAPT	Pathogenic	criteria provided, multiple submitters, no conflicts
14247	NM_001377265.1(MAPT):c.2392C>T (p.Arg798Trp)	MAPT	Pathogenic	criteria provided, multiple submitters, no conflicts
14263	NM_001377265.1(MAPT):c.14G>T (p.Arg5Leu)	MAPT	Pathogenic	no assertion criteria provided
14267	NM_001377265.1(MAPT):c.2231C>T (p.Ser744Leu)	MAPT	Pathogenic	no assertion criteria provided
14269	NM_001377265.1(MAPT):c.2084G>T (p.Gly695Val)	MAPT	Pathogenic	no assertion criteria provided
3075676	NM_001377265.1(MAPT):c.2077C>G (p.Pro693Ala)	MAPT	Likely pathogenic	criteria provided, single submitter
1345546	NM_001377265.1(MAPT):c.10C>A (p.Pro4Thr)	MAPT	Uncertain significance	criteria provided, multiple submitters, no conflicts
1417517	NM_001377265.1(MAPT):c.1807C>T (p.Arg603Cys)	MAPT	Uncertain significance	criteria provided, multiple submitters, no conflicts
1432044	NM_001377265.1(MAPT):c.1366A>G (p.Lys456Glu)	MAPT	Uncertain significance	criteria provided, multiple submitters, no conflicts
3582155	NM_001377265.1(MAPT):c.848G>A (p.Gly283Asp)	MAPT	Uncertain significance	criteria provided, single submitter
452810	NM_001377265.1(MAPT):c.1042T>C (p.Ser348Pro)	MAPT	Uncertain significance	criteria provided, multiple submitters, no conflicts
956359	NM_001377265.1(MAPT):c.89C>T (p.Thr30Ile)	MAPT	Uncertain significance	criteria provided, multiple submitters, no conflicts
962043	NM_001377265.1(MAPT):c.2035G>A (p.Val679Ile)	MAPT	Uncertain significance	criteria provided, multiple submitters, no conflicts
1126880	NM_001377265.1(MAPT):c.1881G>A (p.Ser627=)	MAPT	Likely benign	criteria provided, multiple submitters, no conflicts
1271108	NM_001377265.1(MAPT):c.2074G>A (p.Val692Ile)	MAPT	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
257504	NM_001377265.1(MAPT):c.220+2535A>G	MAPT	Benign	criteria provided, multiple submitters, no conflicts
98197	NM_001377265.1(MAPT):c.914A>G (p.Gln305Arg)	MAPT	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 8 · 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
MAPT	Strong	Autosomal dominant	supranuclear palsy, progressive, 1	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MAPT	Orphanet:100069	Semantic dementia
MAPT	Orphanet:100070	Progressive non-fluent aphasia
MAPT	Orphanet:240071	Classic progressive supranuclear palsy syndrome
MAPT	Orphanet:240085	Progressive supranuclear palsy-predominant parkinsonism syndrome
MAPT	Orphanet:240094	Progressive supranuclear palsy-pure akinesia with gait freezing syndrome
MAPT	Orphanet:240103	Progressive supranuclear palsy-corticobasal syndrome
MAPT	Orphanet:240112	Progressive supranuclear palsy-progressive non-fluent aphasia syndrome
MAPT	Orphanet:275864	Behavioral variant of frontotemporal dementia

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
MAPT	HGNC:6893	ENSG00000186868	P10636	Microtubule-associated protein tau	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MAPT	Microtubule-associated protein tau	Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity.

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)
MAPT	Other/Unknown	no		MAP_tubulin-bd_rpt, Tau, MAP2/MAP4/Tau

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
cortical plate	1
prefrontal cortex	1
superior frontal gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MAPT	141	broad	marker	cortical plate, superior frontal gyrus, prefrontal cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MAPT	7,289

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MAPT	P10636	293

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. 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
Caspase-mediated cleavage of cytoskeletal proteins	1	951.7×	0.005	MAPT
Apoptotic cleavage of cellular proteins	1	475.8×	0.005	MAPT
Apoptotic execution phase	1	475.8×	0.005	MAPT
Activation of AMPK downstream of NMDARs	1	380.7×	0.005	MAPT
Apoptosis	1	167.9×	0.007	MAPT
Programmed Cell Death	1	146.4×	0.007	MAPT
PKR-mediated signaling	1	141.0×	0.007	MAPT

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
plus-end-directed organelle transport along microtubule	1	16852.0×	0.002	MAPT
neurofibrillary tangle assembly	1	8426.0×	0.002	MAPT
negative regulation of protein localization to mitochondrion	1	8426.0×	0.002	MAPT
rRNA metabolic process	1	4213.0×	0.002	MAPT
axonal transport	1	4213.0×	0.002	MAPT
positive regulation of protein localization to synapse	1	4213.0×	0.002	MAPT
negative regulation of mitochondrial fission	1	3370.4×	0.002	MAPT
regulation of long-term synaptic depression	1	3370.4×	0.002	MAPT
regulation of microtubule-based movement	1	2808.7×	0.002	MAPT
intracellular distribution of mitochondria	1	2407.4×	0.002	MAPT
regulation of mitochondrial fission	1	2106.5×	0.002	MAPT
cellular response to brain-derived neurotrophic factor stimulus	1	1872.4×	0.002	MAPT
generation of neurons	1	1532.0×	0.002	MAPT
negative regulation of mitochondrial membrane potential	1	1404.3×	0.002	MAPT
axonal transport of mitochondrion	1	1404.3×	0.002	MAPT
positive regulation of protein localization	1	1404.3×	0.002	MAPT
regulation of microtubule polymerization	1	1123.5×	0.002	MAPT
regulation of calcium-mediated signaling	1	1123.5×	0.002	MAPT
regulation of microtubule polymerization or depolymerization	1	1053.2×	0.002	MAPT
supramolecular fiber organization	1	1053.2×	0.002	MAPT
regulation of cellular response to heat	1	1053.2×	0.002	MAPT
astrocyte activation	1	991.3×	0.002	MAPT
protein polymerization	1	991.3×	0.002	MAPT
response to lead ion	1	936.2×	0.002	MAPT
regulation of chromosome organization	1	936.2×	0.002	MAPT
positive regulation of superoxide anion generation	1	887.0×	0.002	MAPT
microtubule polymerization	1	887.0×	0.002	MAPT
central nervous system neuron development	1	802.5×	0.002	MAPT
positive regulation of microtubule polymerization	1	674.1×	0.003	MAPT
microglial cell activation	1	624.1×	0.003	MAPT

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
MAPT	BEPRIDIL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MAPT	449	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BEPRIDIL	4	MAPT
PHENYLBUTAZONE	4	MAPT
CEFOTAXIME SODIUM	4	MAPT
DIENESTROL	4	MAPT
PROGESTERONE	4	MAPT
CLOTRIMAZOLE	4	MAPT
CHOLECALCIFEROL	4	MAPT
LATANOPROST	4	MAPT
CHLORTHALIDONE	4	MAPT
FLUORESCEIN	4	MAPT
OXCARBAZEPINE	4	MAPT
NABUMETONE	4	MAPT
GLIPIZIDE	4	MAPT
AMIODARONE HYDROCHLORIDE	4	MAPT
TRICLABENDAZOLE	4	MAPT
MESORIDAZINE	4	MAPT
INDIGOTINDISULFONATE	4	MAPT
TRIHEXYPHENIDYL HYDROCHLORIDE	4	MAPT
IMIPRAMINE	4	MAPT
FURAZOLIDONE	4	MAPT
DROPERIDOL	4	MAPT
ARIPIPRAZOLE	4	MAPT
RALOXIFENE HYDROCHLORIDE	4	MAPT
IDARUBICIN	4	MAPT
ACETAMINOPHEN	4	MAPT
ACITRETIN	4	MAPT
CISPLATIN	4	MAPT
CLOBETASOL PROPIONATE	4	MAPT
AMINOSALICYLIC ACID	4	MAPT
TETRABENAZINE	4	MAPT

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
MAPT	184	Binding:180, Functional:4

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
MAPT	184

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

30 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)
BEPRIDIL	4	MAPT
PHENYLBUTAZONE	4	MAPT
CEFOTAXIME SODIUM	4	MAPT
DIENESTROL	4	MAPT
PROGESTERONE	4	MAPT
CLOTRIMAZOLE	4	MAPT
CHOLECALCIFEROL	4	MAPT
LATANOPROST	4	MAPT
CHLORTHALIDONE	4	MAPT
FLUORESCEIN	4	MAPT
OXCARBAZEPINE	4	MAPT
NABUMETONE	4	MAPT
GLIPIZIDE	4	MAPT
AMIODARONE HYDROCHLORIDE	4	MAPT
TRICLABENDAZOLE	4	MAPT
MESORIDAZINE	4	MAPT
INDIGOTINDISULFONATE	4	MAPT
TRIHEXYPHENIDYL HYDROCHLORIDE	4	MAPT
IMIPRAMINE	4	MAPT
FURAZOLIDONE	4	MAPT
DROPERIDOL	4	MAPT
ARIPIPRAZOLE	4	MAPT
RALOXIFENE HYDROCHLORIDE	4	MAPT
IDARUBICIN	4	MAPT
ACETAMINOPHEN	4	MAPT
ACITRETIN	4	MAPT
CISPLATIN	4	MAPT
CLOBETASOL PROPIONATE	4	MAPT
AMINOSALICYLIC ACID	4	MAPT
TETRABENAZINE	4	MAPT

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	MAPT
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: 17.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	13
PHASE2	2
PHASE2/PHASE3	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06122662	PHASE2/PHASE3	COMPLETED	AMX0035 and Progressive Supranuclear Palsy
NCT00139373	PHASE2	UNKNOWN	Study of the Distractibility Syndrome in Patients With Progressive Supranuclear Palsy
NCT03068468	PHASE2	TERMINATED	Study of BIIB092 in Participants With Progressive Supranuclear Palsy
NCT02658916	PHASE1	TERMINATED	Extension Study of BIIB092 in Participants With Progressive Supranuclear Palsy (PSP) Who Participated in CN002003
NCT04468932	Not specified	RECRUITING	Transcranial Magnetic Stimulation in Progressive Supranuclear Palsy
NCT04680130	Not specified	ENROLLING_BY_INVITATION	Clinico-Pathologic-Genetic-Imaging Study of Neurodegenerative and Related Disorders
NCT05792332	Not specified	ACTIVE_NOT_RECRUITING	Integrated Management of Atypical Parkinsonism: A Home-based Patient-Centered Healthcare Delivery Based on Telenursing (IMPACT Study)
NCT05956834	Not specified	ACTIVE_NOT_RECRUITING	A Multi-Modal Remote Monitoring Platform for Frontotemporal Lobar Degeneration (FTLD) Syndromes
NCT06596746	Not specified	RECRUITING	Neurodegenerative Diseases Progression Markers (MARKERS-NDD)
NCT06647641	Not specified	RECRUITING	The CurePSP Genetics Program
NCT07240805	Not specified	NOT_YET_RECRUITING	Digital Health Technologies for Progressive Supranuclear Palsy and Dementia With Lewy Bodies
NCT07316413	Not specified	RECRUITING	Repetitive Transcranial Magnetic Stimulation in Frontotemporal Lobar Degeneration
NCT07429019	Not specified	NOT_YET_RECRUITING	Intraoperative Bupivacaine Injection to Reduce Acute and Chronic Pain After TVT/TVT-O Surgery. Randomized Double-Blind Trial
NCT00368199	Not specified	COMPLETED	Transcranial Duplex Scanning and Single Photon Emission Computer Tomography (SPECT) in Parkinsonian Syndromes
NCT02132052	Not specified	COMPLETED	Defining Phenotypes of Movement Disorders :Parkinson’s Plus Disorders (PD), Essential Tremor (ET), Cortical Basal Degeneration (CBD), Multiple Systems Atrophy (MSA), Magnetoencephalography.
NCT03076671	Not specified	COMPLETED	More Than a Movement Disorder: Applying Palliative Care to Parkinson’s Disease
NCT04858893	Not specified	COMPLETED	Application of Machine Learning Method in Validation of Screening Cognitive Test for Parkinsonisms

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DONEPEZIL	4	1
GOSURANEMAB	2	2

Cohort genes: MAPT
Drugs: Donepezil