Primary dysautonomia

Summary

Primary dysautonomia (MONDO:0021809) is a disease caused by ELP1 (GenCC Definitive), with 1 cohort gene and 31 clinical trials. Top therapeutic interventions include pyridostigmine, baclofen, and esmolol.

At a glance

• Causal gene: ELP1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 2
• Clinical trials: 31

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	primary dysautonomia
Mondo ID	MONDO:0021809
MeSH	D054969
Is cancer (heuristic)	no

Also known as: dysautonomia · dysautonomia, primary · Dysautonomias · Dysautonomias, primary · primary dysautonomia

Data availability: 2 ClinVar variants · 2 GenCC gene-disease records.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › autonomic nervous system disorder › dysautonomia › primary dysautonomia

Subtypes (1): acute cholinergic dysautonomia

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

2 retrieved; paginated sample, class counts are floors:

1 likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
6085	NM_003640.5(ELP1):c.2204+6T>C	ELP1	Pathogenic	criteria provided, multiple submitters, no conflicts
3779610	NM_003640.5(ELP1):c.3222+2T>C	ELP1	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 1 · 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
ELP1	Definitive	Autosomal recessive	primary dysautonomia	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ELP1	Orphanet:1764	Familial dysautonomia

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
ELP1	HGNC:5959	ENSG00000070061	O95163	Elongator complex protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ELP1	Elongator complex protein 1	Component of the elongator complex which is required for multiple tRNA modifications, including mcm5U (5-methoxycarbonylmethyl uridine), mcm5s2U (5-methoxycarbonylmethyl-2-thiouridine), and ncm5U (5-carbamoylmethyl uridine).

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ELP1	Scaffold/PPI	no		Elp1, WD40/YVTN_repeat-like_dom_sf, Beta-prop_ELP1_1st

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
ELP1	291	ubiquitous	marker	adrenal tissue, right adrenal gland cortex, right adrenal gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ELP1	2,733

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ELP1	O95163	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
HATs acetylate histones	1	79.3×	0.013	ELP1

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
tRNA wobble base 5-methoxycarbonylmethyl-2-thiouridinylation	1	5617.3×	5e-04	ELP1
tRNA wobble uridine modification	1	1203.7×	0.001	ELP1
regulation of translation	1	218.9×	0.005	ELP1

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
ELP1	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
ELP1	1	Binding:1

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	ELP1

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)
ELP1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 31.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	25
PHASE2	3
PHASE1	2
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06073886	PHASE2	RECRUITING	Personalized Brain Stimulation to Treat Chronic Concussive Symptoms
NCT00221689	PHASE2	TERMINATED	Intrathecal Baclofen Therapy and Paroxysmal Dysautonomia in Severe Brain-Injured Patients
NCT01343329	PHASE1/PHASE2	WITHDRAWN	Controlling Hyperadrenergic Activity in Neurologic Injury
NCT03674541	PHASE2	COMPLETED	The Exercise Response to Pharmacologic Cholinergic Stimulation in Myalgic Encephalomyelitis / Chronic Fatigue Syndrome
NCT04121338	PHASE1	COMPLETED	Temporary Celiac Ganglion Block as a Test Before Celiac Ganglion Resection for Dysautonomia-Related Bowel Dysmotility
NCT05638620	PHASE1	COMPLETED	Dual Sympathetic Blocks for Patients Experiencing Sympathetically-Mediated Symptoms From Long COVID
NCT02725060	Not specified	ENROLLING_BY_INVITATION	Autoimmune Basis for Postural Tachycardia Syndrome
NCT04806620	Not specified	RECRUITING	Unhide® Project: A Digital Health Platform to Collect Lifestyle Data for Brain Inflammation Research
NCT05041387	Not specified	RECRUITING	Data Collection of Standard Care of Patients in the EMG Section
NCT05400174	Not specified	RECRUITING	Blood Pressure Effects on Cognition and Brain Blood Flow in PD
NCT05741112	Not specified	RECRUITING	The Long COVID-19 Wearable Device Study
NCT06554834	Not specified	RECRUITING	Effects of Osteopathic Technique on Autonomic Nervous System Activity
NCT06863207	Not specified	RECRUITING	Autonomic Reactivity and Personalized Neurostimulation
NCT07405515	Not specified	ACTIVE_NOT_RECRUITING	Pathophysiology of Dysautonomia and Postural Tachycardia Syndrome (POTS) in Post-viral Syndromes and COVID-19
NCT07409363	Not specified	NOT_YET_RECRUITING	Non-invasive Vagus Nerve Stimulation for Chronic Musculoskeletal Pain
NCT07481292	Not specified	ENROLLING_BY_INVITATION	Neuro-Emotional Release: Veins and Endocrine System (NERVE) Therapy for Children With Dysautonomia
NCT00565526	Not specified	COMPLETED	Evaluation of the Role of the Autonomic Nervous System in Sj(SqrRoot)(Delta)Gren s Syndrome
NCT01367977	Not specified	COMPLETED	Head Circumference Growth in Children With Ehlers-Danlos Syndrome Who Develop Dysautonomia Later in Life
NCT01692561	Not specified	COMPLETED	MRI to Assess the Effects of Dysautonomia and Chronic Nausea on Brain Transmitters
NCT02931773	Not specified	UNKNOWN	Autonomic Cardiovascular Neuropathy in Recently Diagnosed DM2 Patients (ACNDM2)
NCT03185247	Not specified	COMPLETED	Implementation of Transdx Group for POTS
NCT03681080	Not specified	COMPLETED	Concentration and Attentional Deficits in POTS and Other Autonomic Neuropathies
NCT04502199	Not specified	UNKNOWN	Dysautonomic Phenotype in Male Patients With MECP2 Mutation
NCT05515640	Not specified	UNKNOWN	Dysautonomia and Systemic Interactions in Traumatic Brain Injury
NCT05566379	Not specified	COMPLETED	Mindfulness in Post Acute Sequelae of SARS-CoV-2 Infection (PASC) Dysautonomia
NCT05630040	Not specified	COMPLETED	VNS for Long-COVID-19
NCT05681455	Not specified	UNKNOWN	Physiotherapy for Persistent Function by Superficial Neuromodulation
NCT05812209	Not specified	COMPLETED	Stellate Ganglion Block to Treat Long COVID 19 Case Series
NCT05855356	Not specified	UNKNOWN	Post Covid-19 Dysautonomia Rehabilitation Randomized Controlled Trial
NCT07029191	Not specified	COMPLETED	Screening for Alterations in the Autonomic Nervous System
NCT07255573	Not specified	COMPLETED	Diagnostic Accuracy of The Water Immersion Wrinkle Test for Small Fiber Neuropathy

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
PYRIDOSTIGMINE	4	2
BACLOFEN	4	1
ESMOLOL	4	1
ISOPROTERENOL	4	1
PROPRANOLOL	4	1