Multiple system atrophy

Summary

Multiple system atrophy (MONDO:0007803) is a disease with 37 cohort genes (55 GWAS associations across 9 studies) and 170 clinical trials. Top therapeutic interventions include droxidopa, midodrine, and carbidopa anhydrous.

At a glance

• Prevalence: 1-9 / 100 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 37
• GWAS associations: 55
• ClinVar variants: 7
• Phenotypes (HPO): 27
• Clinical trials: 170

Clinical features

Epidemiology

Prevalence records

13 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 100 000	1.8	Worldwide	Validated
Point prevalence	1-9 / 100 000	3.5	Worldwide	Validated
Annual incidence	1-9 / 1 000 000	0.7	Iceland	Validated
Annual incidence	1-9 / 100 000	2.1	Sweden	Validated
Annual incidence	1-9 / 1 000 000	0.6	United States	Validated
Annual incidence	1-9 / 1 000 000	0.11	Russian Federation	Validated
Point prevalence	1-9 / 100 000	3.4	Iceland	Validated
Point prevalence	1-9 / 100 000	4.4	United Kingdom	Validated
Point prevalence	1-9 / 100 000	1.9	France	Validated
Point prevalence	1-9 / 100 000	4.9	Italy	Validated
Point prevalence	1-5 / 10 000	10.3	Japan	Validated
Point prevalence	1-9 / 100 000	2.3	Faroe Islands	Validated
Point prevalence	1-9 / 100 000	3.7	Europe	Not yet validated

Signs & symptoms

Clinical features (HPO)

27 HPO clinical features (Orphanet curated; top 27 by frequency):

HPO ID	Term	Frequency
HP:0000640	Gaze-evoked nystagmus	Frequent (30-79%)
HP:0001260	Dysarthria	Frequent (30-79%)
HP:0001300	Parkinsonism	Frequent (30-79%)
HP:0002019	Constipation	Frequent (30-79%)
HP:0002063	Rigidity	Frequent (30-79%)
HP:0002066	Gait ataxia	Frequent (30-79%)
HP:0002067	Bradykinesia	Frequent (30-79%)
HP:0002073	Progressive cerebellar ataxia	Frequent (30-79%)
HP:0002172	Postural instability	Frequent (30-79%)
HP:0002174	Postural tremor	Frequent (30-79%)
HP:0002310	Orofacial dyskinesia	Frequent (30-79%)
HP:0002322	Resting tremor	Frequent (30-79%)
HP:0002359	Frequent falls	Frequent (30-79%)
HP:0002494	Abnormal rapid eye movement sleep	Frequent (30-79%)
HP:0002530	Axial dystonia	Frequent (30-79%)
HP:0004926	Orthostatic hypotension due to autonomic dysfunction	Frequent (30-79%)
HP:0005341	Autonomic bladder dysfunction	Frequent (30-79%)
HP:0007256	Abnormal pyramidal sign	Frequent (30-79%)
HP:0008652	Autonomic erectile dysfunction	Frequent (30-79%)
HP:0010307	Stridor	Frequent (30-79%)
HP:0010536	Central sleep apnea	Frequent (30-79%)
HP:0012658	Abnormal brain FDG positron emission tomography	Frequent (30-79%)
HP:0012670	Orthostatic syncope	Frequent (30-79%)
HP:0030015	Female anorgasmia	Frequent (30-79%)
HP:0030880	Raynaud phenomenon	Frequent (30-79%)
HP:0100595	Camptocormia	Frequent (30-79%)
HP:0012332	Abnormal autonomic nervous system physiology	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	multiple system atrophy
Mondo ID	MONDO:0007803
EFO	EFO:1001050
MeSH	D019578
Orphanet	102
DOID	DOID:4752
ICD-11	1890931931
NCIT	C84909
UMLS	C0393571
MedGen	98276
GARD	0007079
MedDRA	10064060
NORD	1472
Is cancer (heuristic)	no

Also known as: MSA · multisystem atrophy · Shy-Drager syndrome · Shy-dragger syndrome (formerly)

Data availability: 7 ClinVar variants · 55 GWAS associations (9 studies) · 1 GenCC gene-disease record · 57 cell lines.

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › neurodegenerative disease › synucleinopathy › multiple system atrophy

Related subtypes (1): Lewy body dementia

Subtypes (4): striatonigral degeneration, multiple system atrophy, cerebellar type, pure autonomic failure, multiple system atrophy, parkinsonian type

Genetics & variants

GWAS landscape

55 GWAS associations across 9 studies. Top hits map to 24 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs55894236	1e-08	GAB1	C	1.37
rs77075949	1e-08	TENM2	T	7.4
rs11766262	2e-08	RABGEF1	C	1.95
rs4898389	2e-08	CTAG1A - CTAG1B	A	1.69
rs142721461	3e-08	RNU6-745P - LINC02205	A	2.3
rs4900006	1e-07	RN7SKP107 - Y_RNA	?	4.17
chr17:51515165	1e-07		?	3.7
rs4933352	1e-07	LINC01519 - LINC02647	G	0.71
rs78523330	2e-07	FBXO47	G	2.22
rs7715147	3e-07	ELOVL7	C	1.47
rs16872704	4e-07	SUMO2P12 - RN7SKP293	A	1.51
rs79418449	4e-07	DYNLRB2-AS1	C	2.54
rs9303521	7e-07	LINC02210-CRHR1	G	1.32
rs16859966	9e-07	NPM1P28 - LINC02032	G	1.58
chr8:23659564	1e-06		?	3.57
rs10108704	1e-06	ENY2 - PKHD1L1	?	1.69
rs6638956	1e-06	TBL1X	A	1.48
chr16:15689134	2e-06		?	7.69
rs114019803	2e-06	IL12B-AS1	T	3.36
rs12044274	3e-06	LINC02780	T	1.48
rs1413700	3e-06	RREB1	G	1.39
rs116914137	3e-06	MIR302F - RNU6-857P	A	2.17
rs933953	3e-06	LINC02497 - LINC02501	C	0.71
chr5:165784017	4e-06		?	6.67
chr6:101308935	4e-06		?	4.35
chr6:157454156	4e-06		?	2.78
chr8:104768000	4e-06		?	3.57
rs4919206	4e-06	LOXL4 - PYROXD2	G	1.37
rs78274439	4e-06	MDGA2	A	1.73
rs916888	4e-06	WNT3	T	1.35

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST003784	Sailer A	2016	918	3,864	A genome-wide association study in multiple system atrophy.
GCST003179	Federoff M	2015	907	3,866	Genome-wide estimate of the heritability of Multiple System Atrophy.
GCST90558035	Ray A	2026	888	7,128	Chromosome X-wide association study in multiple system atrophy identifies sex-differential risk loci.
GCST90406924	Chia R	2024	888	7,128	Genome sequence analyses identify novel risk loci for multiple system atrophy.
GCST90406925	Chia R	2024	888	7,128	Genome sequence analyses identify novel risk loci for multiple system atrophy.
GCST90244127	Hopfner F	2022	648	2,592	Common Variants Near ZIC1 and ZIC4 in Autopsy-Confirmed Multiple System Atrophy.
GCST90558037	Ray A	2026	472	3,387	Chromosome X-wide association study in multiple system atrophy identifies sex-differential risk loci.
GCST90558036	Ray A	2026	416	3,741	Chromosome X-wide association study in multiple system atrophy identifies sex-differential risk loci.
GCST003783	Sailer A	2016	295	3,864	A genome-wide association study in multiple system atrophy.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	1
Tier 3: regulatory	0
Tier 4: intronic/intergenic	49

MAF distribution

Bucket	Variants
common (>=0.05)	30
low_freq (0.01-0.05)	9
rare (<0.01)	0
unknown	11

Functional consequences

Consequence	Count
intron_variant	25
intergenic_variant	13
unknown	10
non_coding_transcript_exon_variant	1
3_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs55894236	4	143370884	T>A,C,G	0.39	intron_variant	GAB1	1e-08	Tier 4: intronic/intergenic
rs77075949	5	168050512	TC>T	0.07	intron_variant	TENM2	1e-08	Tier 4: intronic/intergenic
rs11766262	7	66699548	C>T	0.41	intron_variant	RABGEF1	2e-08	Tier 4: intronic/intergenic
rs4898389	X	154599376	G>A,C,T	0.14	intergenic_variant	CTAG1A - CTAG1B	2e-08	Tier 4: intronic/intergenic
rs142721461	15	70380309	C>A,T	0.02	intron_variant	RNU6-745P - LINC02205	3e-08	Tier 4: intronic/intergenic
rs4900006	14	89642343	C>A,T		intron_variant	RN7SKP107 - Y_RNA	1e-07	Tier 4: intronic/intergenic
chr17:51515165							1e-07	Tier 4: intronic/intergenic
rs4933352	10	85280795	C>A,G,T	0.48	intergenic_variant	LINC01519 - LINC02647	1e-07	Tier 4: intronic/intergenic
rs78523330	17	38949729	A>G	0.04	intron_variant	FBXO47	2e-07	Tier 4: intronic/intergenic
rs7715147	5	60757393	C>A,G,T	0.26	intron_variant	ELOVL7	3e-07	Tier 4: intronic/intergenic
rs16872704	6	12345461	A>G	0.16	intergenic_variant	SUMO2P12 - RN7SKP293	4e-07	Tier 4: intronic/intergenic
rs79418449	16	80515374	T>C	0.02	intron_variant	DYNLRB2-AS1	4e-07	Tier 4: intronic/intergenic
rs9303521	17	45727828	T>C,G	0.49	intron_variant	LINC02210-CRHR1	7e-07	Tier 4: intronic/intergenic
rs16859966	3	147976678	A>G	0.12	intron_variant	NPM1P28 - LINC02032	9e-07	Tier 4: intronic/intergenic
chr8:23659564							1e-06	Tier 4: intronic/intergenic
rs10108704	8	109350232	G>T	0.05	intergenic_variant	ENY2 - PKHD1L1	1e-06	Tier 4: intronic/intergenic
rs6638956	X	9721087	A>C,G	0.06	intergenic_variant	TBL1X	1e-06	Tier 4: intronic/intergenic
chr16:15689134							2e-06	Tier 4: intronic/intergenic
rs114019803	5	159559041	G>T	0.01	intron_variant	IL12B-AS1	2e-06	Tier 4: intronic/intergenic
rs12044274	1	4063144	A>T	0.35	intron_variant	LINC02780	3e-06	Tier 4: intronic/intergenic
rs1413700	6	7216251	G>A,C	0.21	intron_variant	RREB1	3e-06	Tier 4: intronic/intergenic
rs116914137	18	30589500	G>A	0.02	intergenic_variant	MIR302F - RNU6-857P	3e-06	Tier 4: intronic/intergenic
rs933953	4	31356173	C>A,G,T	0.32	intergenic_variant	LINC02497 - LINC02501	3e-06	Tier 4: intronic/intergenic
chr5:165784017							4e-06	Tier 4: intronic/intergenic
chr6:101308935							4e-06	Tier 4: intronic/intergenic
chr6:157454156							4e-06	Tier 4: intronic/intergenic
chr8:104768000							4e-06	Tier 4: intronic/intergenic
rs4919206	10	98289722	C>A,G	0.49	intron_variant	LOXL4 - PYROXD2	4e-06	Tier 4: intronic/intergenic
rs78274439	14	47461269	A>G	0.15	intron_variant	MDGA2	4e-06	Tier 4: intronic/intergenic
rs916888	17	46785767	T>C	0.25	intron_variant	WNT3	4e-06	Tier 4: intronic/intergenic

ClinVar germline variants

7 retrieved; paginated sample, class counts are floors:

2 conflicting classifications of pathogenicity, 2 risk factor, 2 uncertain significance, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1031932	NM_001358921.2(COQ2):c.663G>A (p.Trp221Ter)	COQ2	Pathogenic	criteria provided, single submitter
60537	NM_001358921.2(COQ2):c.878T>C (p.Val293Ala)	COQ2	risk factor	no assertion criteria provided
60538	NM_001358921.2(COQ2):c.1009C>T (p.Arg337Ter)	COQ2	risk factor	no assertion criteria provided
60536	NM_001358921.2(COQ2):c.232A>G (p.Met78Val)	COQ2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
631951	NM_001358921.2(COQ2):c.138dup (p.Ala47fs)	LOC112997540	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
60539	NM_001358921.2(COQ2):c.1010G>A (p.Arg337Gln)	COQ2	Uncertain significance	criteria provided, single submitter
638372	NM_001377265.1(MAPT):c.889C>A (p.Arg297Ser)	MAPT	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 29 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 2

Dual-evidence genes (GWAS + Mendelian — highest-confidence targets)

Gene	HGNC	Evidence routes
MAPT	MAPT	GWAS, Orphanet
WNT3	WNT3	GWAS, Orphanet

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
COQ2	Moderate	Autosomal recessive	multiple system atrophy	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COQ2	Orphanet:227510	Multiple system atrophy, cerebellar type
COQ2	Orphanet:98933	Multiple system atrophy, parkinsonian type
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
RREB1	Orphanet:567	22q11.2 deletion syndrome
SORD	Orphanet:700508	Distal muscle weakness-foot deformity-elevated sorbitol level-hereditary motor neuropathy
WNT3	Orphanet:3301	Tetraamelia-multiple malformations syndrome
NDE1	Orphanet:2177	Hydranencephaly
NDE1	Orphanet:443162	NDE1-related microhydranencephaly
NDE1	Orphanet:89844	Lissencephaly syndrome, Norman-Roberts type
ARID1B	Orphanet:1465	Coffin-Siris syndrome
ARID1B	Orphanet:251056	6q25.2q25.3 microdeletion syndrome
USP48	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
USP48	Orphanet:96253	Cushing disease
ASXL3	Orphanet:352577	Bainbridge-Ropers syndrome
EDN1	Orphanet:137888	Auriculocondylar syndrome
NKX2-6	Orphanet:3303	Tetralogy of Fallot
NKX2-6	Orphanet:334	Hereditary atrial fibrillation
NKX2-6	Orphanet:3384	Common arterial trunk
FBN2	Orphanet:115	Congenital contractural arachnodactyly
LMX1B	Orphanet:2613	Nail-patella-like renal disease
LMX1B	Orphanet:2614	Nail-patella syndrome
LMX1B	Orphanet:495818	9q33.3q34.11 microdeletion syndrome

Cohort genes → proteins

37 cohort genes, 35 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	35
gwas_and_clinvar	1
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
COQ2	HGNC:25223	ENSG00000173085	Q96H96	4-hydroxybenzoate polyprenyltransferase, mitochondrial	gencc,clinvar
MAPT	HGNC:6893	ENSG00000186868	P10636	Microtubule-associated protein tau	gwas,clinvar
RREB1	HGNC:10449	ENSG00000124782	Q92766	Ras-responsive element-binding protein 1	gwas
SORD	HGNC:11184	ENSG00000140263	Q00796	Sorbitol dehydrogenase	gwas
WNT3	HGNC:12782	ENSG00000108379	P56703	Proto-oncogene Wnt-3	gwas
CDRT7	HGNC:14386	ENSG00000259944		CMT1A duplicated region transcript 7	gwas
RASGRP3	HGNC:14545	ENSG00000152689	Q8IV61	Ras guanyl-releasing protein 3	gwas
ASB1	HGNC:16011	ENSG00000065802	Q9Y576	Ankyrin repeat and SOCS box protein 1	gwas
CARD6	HGNC:16394	ENSG00000132357	Q9BX69	Caspase recruitment domain-containing protein 6	gwas
SLC28A3	HGNC:16484	ENSG00000197506	Q9HAS3	Solute carrier family 28 member 3	gwas
LOXL4	HGNC:17171	ENSG00000138131	Q96JB6	Lysyl oxidase homolog 4	gwas
RIMS2	HGNC:17283	ENSG00000176406	Q9UQ26	Regulating synaptic membrane exocytosis protein 2	gwas
NDE1	HGNC:17619	ENSG00000072864	Q9NXR1	Nuclear distribution protein nudE homolog 1	gwas
CDH4	HGNC:1763	ENSG00000179242	P55283	Cadherin-4	gwas
ARID1B	HGNC:18040	ENSG00000049618	Q8NFD5	AT-rich interactive domain-containing protein 1B	gwas
USP48	HGNC:18533	ENSG00000090686	Q86UV5	Ubiquitin carboxyl-terminal hydrolase 48	gwas
ASCC3	HGNC:18697	ENSG00000112249	Q8N3C0	Activating signal cointegrator 1 complex subunit 3	gwas
EBF2	HGNC:19090	ENSG00000221818	Q9HAK2	Transcription factor COE2	gwas
FOXN3	HGNC:1928	ENSG00000053254	O00409	Forkhead box protein N3	gwas
MDGA2	HGNC:19835	ENSG00000139915	Q7Z553	MAM domain-containing glycosylphosphatidylinositol anchor protein 2	gwas
CRHR1	HGNC:2357	ENSG00000120088	P34998	Corticotropin-releasing factor receptor 1	gwas
ENY2	HGNC:24449	ENSG00000120533	Q9NPA8	Transcription and mRNA export factor ENY2	gwas
ELOVL7	HGNC:26292	ENSG00000164181	A1L3X0	Very long chain fatty acid elongase 7	gwas
ANKFN1	HGNC:26766	ENSG00000153930	Q8N957	Ankyrin repeat and fibronectin type-III domain-containing protein 1	gwas
DDX18	HGNC:2741	ENSG00000088205	Q9NVP1	ATP-dependent RNA helicase DDX18	gwas
ARHGAP44	HGNC:29096	ENSG00000006740	Q17R89	Rho GTPase-activating protein 44	gwas
THSD7B	HGNC:29348	ENSG00000144229	Q9C0I4	Thrombospondin type-1 domain-containing protein 7B	gwas
ASXL3	HGNC:29357	ENSG00000141431	Q9C0F0	Putative Polycomb group protein ASXL3	gwas
TENM2	HGNC:29943	ENSG00000145934	Q9NT68	Teneurin-2	gwas
EDN1	HGNC:3176	ENSG00000078401	P05305	Endothelin-1	gwas
FBXO47	HGNC:31969	ENSG00000204952	Q5MNV8	F-box only protein 47	gwas
NKX2-6	HGNC:32940	ENSG00000180053	A6NCS4	Homeobox protein Nkx-2.6	gwas
MIR548I4	HGNC:35355	ENSG00000221494		microRNA 548i-4	gwas
FBN2	HGNC:3604	ENSG00000138829	P35556	Fibrillin-2	gwas
FOXL1	HGNC:3817	ENSG00000176678	Q12952	Forkhead box protein L1	gwas
LMO7	HGNC:6646	ENSG00000136153	Q8WWI1	LIM domain only protein 7	gwas
LMX1B	HGNC:6654	ENSG00000136944	O60663	LIM homeobox transcription factor 1-beta	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COQ2	4-hydroxybenzoate polyprenyltransferase, mitochondrial	Mediates the second step in the final reaction sequence of coenzyme Q (CoQ) biosynthesis.
MAPT	Microtubule-associated protein tau	Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity.
RREB1	Ras-responsive element-binding protein 1	Transcription factor that binds specifically to the RAS-responsive elements (RRE) of gene promoters.
SORD	Sorbitol dehydrogenase	Polyol dehydrogenase that catalyzes the reversible NAD(+)-dependent oxidation of various sugar alcohols.
WNT3	Proto-oncogene Wnt-3	Ligand for members of the frizzled family of seven transmembrane receptors.
RASGRP3	Ras guanyl-releasing protein 3	Guanine nucleotide exchange factor (GEF) for Ras and Rap1.
ASB1	Ankyrin repeat and SOCS box protein 1	Probable substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.
CARD6	Caspase recruitment domain-containing protein 6	May be involved in apoptosis.
SLC28A3	Solute carrier family 28 member 3	Sodium-dependent, pyrimidine- and purine-selective.
LOXL4	Lysyl oxidase homolog 4	Catalyzes the oxidative deamination of lysine and hydroxylysine residues in collagen and elastin, resulting in the formation of covalent cross-linkages, and the stabilization of collagen and elastin fibers.
RIMS2	Regulating synaptic membrane exocytosis protein 2	Rab effector involved in exocytosis.
NDE1	Nuclear distribution protein nudE homolog 1	Required for centrosome duplication and formation and function of the mitotic spindle.
CDH4	Cadherin-4	Cadherins are calcium-dependent cell adhesion proteins.
ARID1B	AT-rich interactive domain-containing protein 1B	Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
USP48	Ubiquitin carboxyl-terminal hydrolase 48	Deubiquitinase that recognizes and hydrolyzes the peptide bond at the C-terminal Gly of ubiquitin.
ASCC3	Activating signal cointegrator 1 complex subunit 3	ATPase involved both in DNA repair and rescue of stalled ribosomes. 3’-5’ DNA helicase involved in repair of alkylated DNA: promotes DNA unwinding to generate single-stranded substrate needed for ALKBH3, enabling ALKBH3 to process alkylate…
EBF2	Transcription factor COE2	Transcription factor that, in osteoblasts, activates the decoy receptor for RANKL, TNFRSF11B, which in turn regulates osteoclast differentiation.
FOXN3	Forkhead box protein N3	Acts as a transcriptional repressor.
MDGA2	MAM domain-containing glycosylphosphatidylinositol anchor protein 2	May be involved in cell-cell interactions.
CRHR1	Corticotropin-releasing factor receptor 1	G-protein coupled receptor for CRH (corticotropin-releasing factor) and UCN (urocortin).
ENY2	Transcription and mRNA export factor ENY2	Involved in mRNA export coupled transcription activation by association with both the TREX-2 and the SAGA complexes.
ELOVL7	Very long chain fatty acid elongase 7	Catalyzes the first and rate-limiting reaction of the four reactions that constitute the long-chain fatty acids elongation cycle.
ANKFN1	Ankyrin repeat and fibronectin type-III domain-containing protein 1	May play a role in neuronal function.
DDX18	ATP-dependent RNA helicase DDX18	ATP-dependent RNA helicase that plays a role in the regulation of R-loop homeostasis in both endogenous R-loop-prone regions and at sites of DNA damage.
ARHGAP44	Rho GTPase-activating protein 44	GTPase-activating protein (GAP) that stimulates the GTPase activity of Rho-type GTPases.
ASXL3	Putative Polycomb group protein ASXL3	Putative Polycomb group (PcG) protein.
TENM2	Teneurin-2	Involved in neural development, regulating the establishment of proper connectivity within the nervous system.
EDN1	Endothelin-1	Endothelins are endothelium-derived vasoconstrictor peptides.
FBXO47	F-box only protein 47	Probably recognizes and binds to some phosphorylated proteins and promotes their ubiquitination and degradation.
NKX2-6	Homeobox protein Nkx-2.6	Acts as a transcriptional activator.
FBN2	Fibrillin-2	Fibrillins are structural components of 10-12 nm extracellular calcium-binding microfibrils, which occur either in association with elastin or in elastin-free bundles.
FOXL1	Forkhead box protein L1	Transcription factor required for proper proliferation and differentiation in the gastrointestinal epithelium.
LMX1B	LIM homeobox transcription factor 1-beta	Transcription factor involved in the regulation of podocyte-expressed genes.

Protein-family classification

Druggable: 7 · Difficult: 11 · Unknown: 19 · Druggable fraction: 0.19

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
Transcription factor	9	2.0×	0.205
Antibody/Immunoglobulin	2	1.6×	0.794
Protease	1	1.0×	0.794
Enzyme (other)	3	1.0×	0.794
Scaffold/PPI	2	0.9×	0.794
Other/Unknown	19	0.9×	0.794
GPCR	1	0.7×	0.794

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
COQ2	Enzyme (other)	yes	2.5.1.39	UbiA_prenyltransferase, HB_polyprenyltransferase-like, UbiA_prenylTrfase_CS
MAPT	Other/Unknown	no		MAP_tubulin-bd_rpt, Tau, MAP2/MAP4/Tau
RREB1	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, RREB1
SORD	Enzyme (other)	yes	1.1.1.14	ADH_Zn_CS, GroES-like_sf, ADH-like_C
WNT3	Other/Unknown	no		Wnt, Wnt3, Wnt_CS
CDRT7	Other/Unknown	no
RASGRP3	Other/Unknown	no		Ras-like_Gua-exchang_fac_N, RASGEF_cat_dom, EF_hand_dom
ASB1	Scaffold/PPI	no		SOCS_box, Ankyrin_rpt, SOCS_box-like_dom_sf
CARD6	Other/Unknown	no		CARD, DEATH-like_dom_sf, Apoptosis_Repressor_CARD
SLC28A3	Other/Unknown	no		CNT_N_dom, C_nuclsd_transpt, Gate_dom
LOXL4	Other/Unknown	no		SRCR, Lysyl_oxidase, Lysyl_oxidase_CS
RIMS2	Transcription factor	no		C2_dom, PDZ, Rab_BD
NDE1	Other/Unknown	no		NUDE_dom, NUDE
CDH4	Other/Unknown	no		Cadherin_Y-type_LIR, Cadherin-like_dom, Cadherin_pro_dom
ARID1B	Other/Unknown	no		ARID_dom, BAF250/Osa, BAF250_C
USP48	Protease	yes		Ubiquitin-like_dom, Peptidase_C19_UCH, Pept_C19_DUSP
ASCC3	Other/Unknown	no		Helicase_C-like, AAA+_ATPase, Sec63-dom
EBF2	Transcription factor	no		IPT_dom, Transcription_factor_COE, Ig-like_fold
FOXN3	Transcription factor	no		Fork_head_dom, TF_fork_head_CS_1, TF_fork_head_CS_2
MDGA2	Antibody/Immunoglobulin	yes		MAM_dom, Ig_sub2, Ig_sub
CRHR1	GPCR	yes		GPCR_2_secretin-like, GPCR_2_extracellular_dom, GPCR_2_CRF_rcpt
ENY2	Transcription factor	no		TF_ENY2, TF_EnY2_sf
ELOVL7	Enzyme (other)	yes	2.3.1.199	ELO_fam, ELO_CS, ELOVL7
ANKFN1	Antibody/Immunoglobulin	yes		Ankyrin_rpt, FN3_dom, Ig-like_fold
DDX18	Other/Unknown	no		RNA-helicase_DEAD-box_CS, Helicase_C-like, DEAD/DEAH_box_helicase_dom
ARHGAP44	Scaffold/PPI	no		RhoGAP_dom, BAR_dom, Rho_GTPase_activation_prot
THSD7B	Other/Unknown	no		TSP1_rpt, TSP1_rpt_sf, TSP1_spondin_dom
ASXL3	Other/Unknown	no		Asxl_HARE-HTH, ASX/ASX-like, ASX-like_PHD
TENM2	Other/Unknown	no		EGF, EGF-like_Ca-bd_dom, YD
EDN1	Other/Unknown	no		Endothln-like_toxin, Endothelin_toxin_CS, Endothelin
FBXO47	Other/Unknown	no		F-box_dom, F-box-like_dom_sf, FBXO47
NKX2-6	Transcription factor	no		HD, Homeodomain-like_sf, Homeobox_CS
MIR548I4	Other/Unknown	no
FBN2	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom
FOXL1	Transcription factor	no		Fork_head_dom, TF_fork_head_CS_1, TF_fork_head_CS_2
LMO7	Transcription factor	no		PDZ, CH_dom, Znf_LIM
LMX1B	Transcription factor	no		HD, Znf_LIM, Homeodomain-like_sf

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	4
broad (>20)	33
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	6
cortical plate	4
buccal mucosa cell	4
secondary oocyte	4
cartilage tissue	3
middle temporal gyrus	3
sural nerve	3
oocyte	3
primordial germ cell in gonad	3
hypothalamus	2
C1 segment of cervical spinal cord	2
corpus callosum	2
apex of heart	2
epithelial cell of pancreas	2
lateral nuclear group of thalamus	2
colonic epithelium	2
ventricular zone	2
adrenal tissue	2
calcaneal tendon	2
cerebellar hemisphere	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COQ2	284	ubiquitous	marker	skeletal muscle tissue of biceps brachii, skeletal muscle tissue of rectus abdominis, gingival epithelium
MAPT	141	broad	marker	cortical plate, superior frontal gyrus, prefrontal cortex
RREB1	278	ubiquitous	marker	buccal mucosa cell, epithelium of nasopharynx, oral cavity
SORD	199	ubiquitous	marker	right lobe of thyroid gland, left lobe of thyroid gland, thyroid gland
WNT3	129	broad	yes	skin of abdomen, zone of skin, hypothalamus
CDRT7	16		yes	male germ line stem cell (sensu Vertebrata) in testis, Brodmann (1909) area 9, liver
RASGRP3	255	ubiquitous	marker	corpus callosum, inferior vagus X ganglion, C1 segment of cervical spinal cord
ASB1	270	ubiquitous	marker	apex of heart, C1 segment of cervical spinal cord, nucleus accumbens
CARD6	232	ubiquitous	marker	epithelial cell of pancreas, esophagus squamous epithelium, palpebral conjunctiva
SLC28A3	174	broad	marker	cartilage tissue, secondary oocyte, germinal epithelium of ovary
LOXL4	194	broad	marker	tibia, islet of Langerhans, cartilage tissue
RIMS2	198	broad	marker	lateral nuclear group of thalamus, endothelial cell, middle temporal gyrus
NDE1	134	ubiquitous	marker	colonic epithelium, ventricular zone, corpus callosum
CDH4	118	broad	yes	ventricular zone, ganglionic eminence, adrenal tissue
ARID1B	256	ubiquitous	marker	bone marrow cell, colonic epithelium, sural nerve
USP48	292	ubiquitous	marker	calcaneal tendon, cerebellar hemisphere, right hemisphere of cerebellum
ASCC3	278	ubiquitous	marker	decidua, secondary oocyte, calcaneal tendon
EBF2	185	broad	marker	dorsal root ganglion, secondary oocyte, oocyte
FOXN3	300	ubiquitous	marker	paraflocculus, tendon of biceps brachii, nipple
MDGA2	85	broad	marker	cortical plate, male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad
CRHR1	113	tissue_specific	yes	right hemisphere of cerebellum, cerebellar cortex, cerebellar hemisphere
ENY2	288	ubiquitous	marker	tendon of biceps brachii, oocyte, monocyte
ELOVL7	228	ubiquitous	marker	upper arm skin, epithelial cell of pancreas, penis
ANKFN1	148	tissue_specific	marker	buccal mucosa cell, male germ line stem cell (sensu Vertebrata) in testis, bronchial epithelial cell
DDX18	291	ubiquitous	marker	oocyte, lower lobe of lung, cauda epididymis
ARHGAP44	250	broad	marker	lateral nuclear group of thalamus, Brodmann (1909) area 23, middle temporal gyrus
THSD7B	151	broad	marker	male germ line stem cell (sensu Vertebrata) in testis, pigmented layer of retina, cortical plate
ASXL3	205	broad	marker	buccal mucosa cell, secondary oocyte, cortical plate
TENM2	207	broad	marker	left ventricle myocardium, cardiac muscle of right atrium, middle temporal gyrus
EDN1	253	ubiquitous	marker	lower lobe of lung, buccal mucosa cell, right lung

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MAPT	7,289
DDX18	4,969
SORD	3,915
EDN1	3,756
ASCC3	2,898
ENY2	2,844
CRHR1	2,695
FBN2	2,570
COQ2	2,160
ARID1B	2,131

Intra-cohort edges

A	B	Sources
CRHR1	WNT3	string_interaction
ELOVL7	FBXO47	string_interaction

Structural data

PDB: 16 · AlphaFold-only: 19 · No structure: 2

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MAPT	P10636	293
EDN1	P05305	17
CRHR1	P34998	11
DDX18	Q9NVP1	11
SORD	Q00796	3
RIMS2	Q9UQ26	2
ARID1B	Q8NFD5	2
ASCC3	Q8N3C0	2
FOXN3	O00409	2
TENM2	Q9NT68	2
WNT3	P56703	1
SLC28A3	Q9HAS3	1
NDE1	Q9NXR1	1
ENY2	Q9NPA8	1
ELOVL7	A1L3X0	1
LMO7	Q8WWI1	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FBXO47	Q5MNV8	87.21
LOXL4	Q96JB6	86.43
COQ2	Q96H96	85.64
MDGA2	Q7Z553	84.96
USP48	Q86UV5	81.44
ASB1	Q9Y576	80.61
CDH4	P55283	79.02
EBF2	Q9HAK2	73.38
LMX1B	O60663	70.79
RASGRP3	Q8IV61	70.51
THSD7B	Q9C0I4	67.23
ANKFN1	Q8N957	66.55
ARHGAP44	Q17R89	66.39
NKX2-6	A6NCS4	64.31
FOXL1	Q12952	64.30
CARD6	Q9BX69	55.25
RREB1	Q92766	48.28
ASXL3	Q9C0F0	39.70
FBN2	P35556

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 116. Enrichment computed across 37 evidence-associated genes (23 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 23 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
ALKBH3 mediated reversal of alkylation damage	1	124.1×	0.203	ASCC3
Fructose biosynthesis	1	124.1×	0.203	SORD
Activation of RAS in B cells	1	99.3×	0.203	RASGRP3
Formation of xylulose-5-phosphate	1	82.8×	0.203	SORD
DNA Damage Reversal	1	70.9×	0.203	ASCC3
Reversal of alkylation damage by DNA dioxygenases	1	70.9×	0.203	ASCC3
Elastic fibre formation	2	29.2×	0.203	LOXL4, FBN2
Class B/2 (Secretin family receptors)	2	16.6×	0.203	WNT3, CRHR1
Ribavirin ADME	1	45.1×	0.250	SLC28A3
Caspase-mediated cleavage of cytoskeletal proteins	1	41.4×	0.250	MAPT
Transport of nucleosides and free purine and pyrimidine bases across the plasma membrane	1	41.4×	0.250	SLC28A3
Ubiquinol biosynthesis	1	38.2×	0.250	COQ2
Formation of the canonical BAF (cBAF) complex	1	27.6×	0.259	ARID1B
Crosslinking of collagen fibrils	1	24.8×	0.259	LOXL4
Azathioprine ADME	1	21.6×	0.259	SLC28A3
Apoptotic cleavage of cellular proteins	1	20.7×	0.259	MAPT
Apoptotic execution phase	1	20.7×	0.259	MAPT
Collagen formation	1	19.9×	0.259	LOXL4
Synthesis of very long-chain fatty acyl-CoAs	1	19.9×	0.259	ELOVL7
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	1	19.9×	0.259	ARID1B
Class I MHC mediated antigen processing & presentation	2	6.1×	0.259	ASB1, LMO7
Post-translational protein modification	4	3.3×	0.259	ASB1, MDGA2, THSD7B, LMO7
WNT ligand biogenesis and trafficking	1	18.4×	0.261	WNT3
Myogenesis	1	16.6×	0.261	CDH4
Activation of AMPK downstream of NMDARs	1	16.6×	0.261	MAPT
Transcriptional regulation of brown and beige adipocyte differentiation by EBF2	1	16.6×	0.261	EBF2
Regulation of endogenous retroelements	1	16.0×	0.261	ARID1B
Molecules associated with elastic fibres	1	13.4×	0.271	FBN2
Defective B3GALTL causes PpS	1	13.4×	0.271	THSD7B
O-glycosylation of TSR domain-containing proteins	1	13.1×	0.271	THSD7B

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 34 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
visceral mesoderm-endoderm interaction involved in midgut development	1	495.6×	0.054	FOXL1
pyrimidine nucleoside transport	1	495.6×	0.054	SLC28A3
rhythmic excitation	1	495.6×	0.054	EDN1
Spemann organizer formation at the anterior end of the primitive streak	1	495.6×	0.054	WNT3
regulation of establishment of bipolar cell polarity	1	495.6×	0.054	ANKFN1
plus-end-directed organelle transport along microtubule	1	495.6×	0.054	MAPT
histamine secretion	1	247.8×	0.054	EDN1
D-sorbitol catabolic process	1	247.8×	0.054	SORD
phospholipase D-activating G protein-coupled receptor signaling pathway	1	247.8×	0.054	EDN1
cellular response to human chorionic gonadotropin stimulus	1	247.8×	0.054	EDN1
positive regulation of collateral sprouting in absence of injury	1	247.8×	0.054	WNT3
chromosome localization	1	247.8×	0.054	NDE1
xylitol catabolic process	1	247.8×	0.054	SORD
xylitol metabolic process	1	247.8×	0.054	SORD
corticotropin secretion	1	247.8×	0.054	CRHR1
positive regulation of chemokine-mediated signaling pathway	1	247.8×	0.054	EDN1
regulation of neurotransmitter receptor transport, endosome to postsynaptic membrane	1	247.8×	0.054	ARHGAP44
neurofibrillary tangle assembly	1	247.8×	0.054	MAPT
negative regulation of protein localization to mitochondrion	1	247.8×	0.054	MAPT
regulation of corticosterone secretion	1	247.8×	0.054	CRHR1
regulation of signaling	1	165.2×	0.054	LMO7
response to prostaglandin F	1	165.2×	0.054	EDN1
atrial cardiac muscle cell development	1	165.2×	0.054	NKX2-6
cellular response to mineralocorticoid stimulus	1	165.2×	0.054	EDN1
endothelin receptor signaling pathway involved in heart process	1	165.2×	0.054	EDN1
retrograde trans-synaptic signaling by trans-synaptic protein complex	1	165.2×	0.054	TENM2
negative regulation of phospholipase C/protein kinase C signal transduction	1	165.2×	0.054	EDN1
semaphorin-plexin signaling pathway involved in axon guidance	1	165.2×	0.054	EDN1
neural crest cell fate commitment	1	123.9×	0.054	EDN1
vein smooth muscle contraction	1	123.9×	0.054	EDN1

Therapeutics

Drugs indicated for this disease

1 approved, 5 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Droxidopa	Approved (phase 4)
Ampreloxetine	Phase 3 (in late-stage trials)
Epigalocatechin Gallate	Phase 3 (in late-stage trials)
Rifampin	Phase 3 (in late-stage trials)
Riluzole	Phase 3 (in late-stage trials)
Verdiperstat	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Exenatide, Fluoxetine, Human Immunoglobulin G, Inosine, Insulin Human, Lithium Carbonate, Safinamide, Sirolimus, Sodium Chloride.

Drug target analysis

Approved (phase 4): 5 · Phase ≥3: 5 · Phased (≥1): 7 · Undrugged: 30

Druggability breadth: 10 of 37 evidence-associated genes (27%) 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
SORD	EPALRESTAT
SLC28A3	ADENOSINE
LOXL4	PYRITHIONE
CRHR1	CRINECERFONT

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MAPT	449	4
CRHR1	6	4
LOXL4	3	4
SORD	2	4
SLC28A3	2	4
RASGRP3	1	2
ENY2	1	2
COQ2	0	0
RREB1	0	0
WNT3	0	0

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): 3.

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

Symbol	Assays	Type breakdown
CRHR1	193	Binding:139, Functional:54
MAPT	184	Binding:180, Functional:4
RASGRP3	20	Binding:20
SORD	17	Binding:16, Functional:1
ENY2	7	Binding:7
WNT3	5	Functional:3, Binding:2
SLC28A3	3	ADMET:2, Binding:1
LOXL4	3	Binding:3
ELOVL7	3	Binding:3
DDX18	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
COQ2	2.5.1.39	4-hydroxybenzoate polyprenyltransferase
SORD	1.1.1.14	L-iditol 2-dehydrogenase
ELOVL7	2.3.1.199	very-long-chain 3-oxoacyl-CoA synthase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
MAPT	184
CRHR1	193

Pharmacogenomics

Cohort genes with a PharmGKB record: 37; 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)	5	MAPT, SORD, SLC28A3, LOXL4, CRHR1
B	Phased (≥1) drug, not yet approved	2	RASGRP3, ENY2
C	Druggable family + PDB, no drug	1	ELOVL7
D	Druggable family + AlphaFold only, no drug	4	COQ2, USP48, MDGA2, ANKFN1
E	Difficult family or no structure, no drug	25	RREB1, WNT3, CDRT7, ASB1, CARD6, RIMS2, NDE1, CDH4, ARID1B, ASCC3 (+15 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
COQ2	0	—
RREB1	0	—
WNT3	5	—
CDRT7	0	—
ASB1	0	—
CARD6	0	—
RIMS2	0	—
NDE1	0	—
CDH4	0	—
ARID1B	0	—
USP48	0	—
ASCC3	0	—
EBF2	0	—
FOXN3	0	—
MDGA2	0	—
ELOVL7	3	—
ANKFN1	0	—
DDX18	1	—
ARHGAP44	0	—
THSD7B	0	—
ASXL3	0	—
TENM2	0	—
EDN1	0	—
FBXO47	0	—
NKX2-6	0	—
MIR548I4	0	—
FBN2	0	—
FOXL1	0	—
LMO7	0	—
LMX1B	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 170.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	99
PHASE2	27
PHASE1	18
PHASE3	10
EARLY_PHASE1	8
PHASE1/PHASE2	4
PHASE4	2
PHASE2/PHASE3	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03924414	PHASE4	ACTIVE_NOT_RECRUITING	Trial of Parkinson’s And Zoledronic Acid
NCT00822913	PHASE4	UNKNOWN	Botulinum A Toxin in Patients With Parkinson’s Disease
NCT06706622	PHASE3	ACTIVE_NOT_RECRUITING	A Trial of Amlenetug (Lu AF82422) in Participants With Multiple System Atrophy (MSA)
NCT07446894	PHASE3	RECRUITING	MSA-01 in Multiple System Atrophy
NCT07518810	PHASE2/PHASE3	NOT_YET_RECRUITING	Efficacy and Safety of Butylphthalide in the Treatment of Multiple System Atrophy
NCT00211224	PHASE3	TERMINATED	Neuroprotection and Natural History in Parkinson’s Plus Syndromes (NNIPPS)
NCT00738062	PHASE3	COMPLETED	Open-Label Clinical Study of Droxidopa in Patients With Neurogenic Orthostatic Hypotension (NOH)
NCT01287221	PHASE3	TERMINATED	Study of Rifampicin in Multiple System Atrophy
NCT02008721	PHASE3	COMPLETED	Progression Rate of MSA Under EGCG Supplementation as Anti-Aggregation-Approach
NCT02071459	PHASE2/PHASE3	COMPLETED	Efficacy of L-threo DOPS on Orthostatic Hypotension Symptoms and Other Non-motor Symptoms in Patients With MSA
NCT03829657	PHASE3	TERMINATED	Phase 3 Clinical Effect Durability of TD-9855 for Treating Symptomatic nOH in Subjects With Primary Autonomic Failure
NCT03901638	PHASE3	TERMINATED	Tllsh2910 for Ataxia and Gut Microbiota Alteration in Patients of Multiple System Atrophy
NCT03952806	PHASE3	COMPLETED	Study of BHV-3241 in Participants With Multiple System Atrophy
NCT04193527	PHASE3	COMPLETED	A Study to Evaluate the Diagnostic Efficacy of DaTSCAN™ Ioflupane (123I) Injection in Single Photon Emission Computed Tomography (SPECT) for the Diagnosis of Parkinsonian Syndrome (PS) in Chinese Patients
NCT02315027	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Mesenchymal Stem Cell Therapy in Multiple System Atrophy
NCT05104476	PHASE2	ACTIVE_NOT_RECRUITING	A Study of Lu AF82422 in Participants With Multiple System Atrophy
NCT05167721	PHASE2	ACTIVE_NOT_RECRUITING	Randomized Double-Blind Placebo-Controlled Adaptive Design Trial Of Intrathecally Administered Autologous Mesenchymal Stem Cells In Multiple System Atrophy
NCT05923866	PHASE2	ACTIVE_NOT_RECRUITING	A Phase 2 Study of ONO-2808 in Patients With Multiple System Atrophy
NCT06162013	PHASE2	RECRUITING	The NADAPT Study: a Randomized Double-blind Trial of NAD Replenishment Therapy for Atypical Parkinsonism
NCT06568237	PHASE2	RECRUITING	A Trial to Test if TEV-56286 is Effective for Treatment of Participants With Multiple System Atrophy
NCT06671938	PHASE2	ACTIVE_NOT_RECRUITING	Safety, Tolerability, and Pharmacokinetics of Exidavnemab in Patients With Parkinson’s Disease and Patients With Multiple System Atrophy
NCT06848231	PHASE2	RECRUITING	A Phase 2 Study of YA-101 in Patients With Multiple System Atrophy
NCT06868628	PHASE2	RECRUITING	A Phase 2a Study of Foralumab Nasal in Patients With Multiple System Atrophy (MSA)
NCT07197866	PHASE2	RECRUITING	An Extension Trial to Test if TEV-56286 is Effective in Relieving Multiple System Atrophy
NCT07465198	PHASE2	NOT_YET_RECRUITING	Autologous Stem Cell Therapy in Patients With Multiple System Atrophy
NCT00547911	PHASE1/PHASE2	TERMINATED	Augmenting Effects of L-DOPS With Carbidopa and Entacapone
NCT00750867	PHASE2	COMPLETED	Treatment of Multiple System Atrophy Using Intravenous Immunoglobulins
NCT00758849	PHASE2	UNKNOWN	Fipamezole in Neurogenic Orthostatic Hypotension
NCT00911365	PHASE2	COMPLETED	Trial of Autologous Mesenchymal Stem Cells in Patients With Multiple System Atrophy
NCT00977665	PHASE2	COMPLETED	Clinical Trial to Assess Efficacy, Safety, and Tolerability of Rasagiline Mesylate 1 mg in Patients With Multiple System Atrophy of the Parkinsonian Subtype (MSA-P)
NCT00997672	PHASE2	TERMINATED	Lithium in Multiple System Atrophy
NCT01146548	PHASE2	COMPLETED	Fluoxetine in Multiple System Atrophy Patients
NCT02064166	PHASE2	COMPLETED	Treatment of Parkinson Disease and Multiple System Atrophy Using Intranasal Insulin.
NCT03033680	PHASE1/PHASE2	COMPLETED	Establishing 18F-PBR06 PET Imaging as a Viable Pharmacodynamic Endpoint in MSA
NCT03403309	PHASE2	COMPLETED	Inosine 5’-Monophosphate to Raise of Serum Uric Acid Level in Patients With Multiple System Atrophy: a Multi-center, Randomized Controlled, Double Blind, Parallel Assigned Clinical Trial
NCT03446807	PHASE2	WITHDRAWN	Safety and Efficacy of Droxidopa for Fatigue in Patients With Parkinsonism
NCT03482297	PHASE1/PHASE2	COMPLETED	Automated Abdominal Binder for Orthostatic Hypotension
NCT03589976	PHASE2	TERMINATED	A Futility Trial of Sirolimus in Multiple System Atrophy
NCT03753763	PHASE2	COMPLETED	Safinamide for Multiple System Atrophy (MSA)
NCT04184063	PHASE2	COMPLETED	Study of NBMI Treatment in Patients With Atypical Parkinsons (PSP or MSA)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DROXIDOPA	4	6
MIDODRINE	4	4
CARBIDOPA ANHYDROUS	4	3
RASAGILINE	4	3
ZOLEDRONIC ACID ANHYDROUS	4	3
PSEUDOEPHEDRINE	4	2
TRIMETHAPHAN	4	2
CAPTOPRIL	4	1
DOMPERIDONE	4	1
ENTACAPONE	4	1
FLUDROCORTISONE ACETATE	4	1
FLUORODOPA F 18	4	1
FLUTEMETAMOL	4	1
LITHIUM CARBONATE	4	1
METOPROLOL	4	1
NEBIVOLOL	4	1
RIFAMPIN	4	1
RILUZOLE	4	1
SAFINAMIDE MESYLATE	4	1
VERDIPERSTAT	3	3
AMPRELOXETINE	3	1
NICOTINAMIDE RIBOSIDE	3	1
RAC-3-N-BUTYLPHTHALIDE	3	1
AMLENETUG	2	2
PBT-434	2	2
BQ-123	2	1
FIPAMEZOLE	2	1
FLUDROCORTISONE	2	1
INDENEBART	2	1
TALFIRASTIDE	2	1