Tremor, hereditary essential, 1

Summary

Tremor, hereditary essential, 1 (MONDO:0008590) is a disease with 1 cohort gene and 1 clinical trial.

At a glance

• Cohort genes: 1
• ClinVar variants: 14
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	tremor, hereditary essential, 1
Mondo ID	MONDO:0008590
MeSH	C536545
OMIM	190300
DOID	DOID:0111428
UMLS	C1860861
MedGen	349909
Is cancer (heuristic)	no

Also known as: DRD3 essential tremor · essential tremor caused by mutation in DRD3 · essential tremor, hereditary, 1 · ETM1 · FET1 · tremor familial essential, 1 · tremor hereditary essential, 1 · tremor, hereditary essential, 1 · tremor, hereditary essential, type 1

Data availability: 14 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › movement disorder › essential tremor › tremor, hereditary essential, 1

Related subtypes (5): tremor, hereditary essential, 2, tremor, hereditary essential, 3, tremor, hereditary essential, 4, tremor, hereditary essential, 5, tremor, hereditary essential, 6

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

14 retrieved; paginated sample, class counts are floors:

6 likely benign, 4 benign, 2 benign/likely benign, 1 uncertain significance, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
899696	NM_000796.6(DRD3):c.406G>A (p.Val136Ile)	DRD3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1711864	NM_000796.6(DRD3):c.404C>A (p.Pro135His)	DRD3	Uncertain significance	criteria provided, single submitter
16770	NM_000796.6(DRD3):c.25G>A (p.Gly9Ser)	DRD3	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
342595	NM_000796.6(DRD3):c.1077C>T (p.His359=)	DRD3	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
342596	NM_000796.6(DRD3):c.987A>G (p.Gln329=)	DRD3	Benign	criteria provided, multiple submitters, no conflicts
342598	NM_000796.6(DRD3):c.720G>A (p.Gln240=)	DRD3	Benign	criteria provided, multiple submitters, no conflicts
342599	NM_000796.6(DRD3):c.691T>A (p.Cys231Ser)	DRD3	Likely benign	criteria provided, single submitter
342603	NM_000796.6(DRD3):c.51A>G (p.Ala17=)	DRD3	Benign	criteria provided, multiple submitters, no conflicts
342605	NM_000796.6(DRD3):c.-105G>A	DRD3	Likely benign	criteria provided, multiple submitters, no conflicts
342607	NM_000796.6(DRD3):c.-153T>G	DRD3	Likely benign	criteria provided, single submitter
342608	NM_000796.6(DRD3):c.-252C>T	DRD3	Likely benign	criteria provided, single submitter
342610	NM_000796.6(DRD3):c.-286A>C	DRD3	Likely benign	criteria provided, single submitter
342612	NM_000796.6(DRD3):c.-333G>A	DRD3	Benign	criteria provided, multiple submitters, no conflicts
899697	NM_000796.6(DRD3):c.112G>A (p.Ala38Thr)	DRD3	Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 0 · 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
DRD3	Limited	Autosomal dominant	tremor, hereditary essential, 1	2

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
DRD3	HGNC:3024	ENSG00000151577	P35462	D(3) dopamine receptor	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DRD3	D(3) dopamine receptor	Dopamine receptor that is primarily expressed in limbic areas of the brain and is involved in the modulation of cognitive, emotional, and endocrine functions.

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
GPCR	1	23.9×	0.042

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DRD3	GPCR	yes		GPCR_Rhodpsn, Dopamine_rcpt, Dopamine_D3_rcpt

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
endometrium epithelium	1
male germ line stem cell (sensu Vertebrata) in testis	1
metanephric glomerulus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DRD3	25		marker	male germ line stem cell (sensu Vertebrata) in testis, metanephric glomerulus, endometrium epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DRD3	1,539

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DRD3	P35462	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
Dopamine receptors	1	2284.0×	9e-04	DRD3
G alpha (i) signalling events	1	39.0×	0.026	DRD3

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
musculoskeletal movement, spinal reflex action	1	8426.0×	0.002	DRD3
acid secretion	1	5617.3×	0.002	DRD3
response to histamine	1	4213.0×	0.002	DRD3
positive regulation of dopamine receptor signaling pathway	1	4213.0×	0.002	DRD3
adenylate cyclase-inhibiting dopamine receptor signaling pathway	1	3370.4×	0.002	DRD3
regulation of dopamine uptake involved in synaptic transmission	1	2407.4×	0.002	DRD3
phospholipase C-activating dopamine receptor signaling pathway	1	2106.5×	0.002	DRD3
regulation of potassium ion transport	1	1872.4×	0.002	DRD3
G protein-coupled receptor internalization	1	1685.2×	0.002	DRD3
negative regulation of synaptic transmission, glutamatergic	1	1685.2×	0.002	DRD3
adenylate cyclase-activating dopamine receptor signaling pathway	1	1532.0×	0.002	DRD3
negative regulation of cytosolic calcium ion concentration	1	1296.3×	0.002	DRD3
regulation of dopamine secretion	1	1203.7×	0.002	DRD3
response to morphine	1	1203.7×	0.002	DRD3
negative regulation of oligodendrocyte differentiation	1	1123.5×	0.002	DRD3
prepulse inhibition	1	1123.5×	0.002	DRD3
dopamine metabolic process	1	991.3×	0.002	DRD3
negative regulation of protein secretion	1	887.0×	0.002	DRD3
behavioral response to cocaine	1	842.6×	0.002	DRD3
arachidonate secretion	1	702.2×	0.002	DRD3
negative regulation of blood pressure	1	648.1×	0.002	DRD3
response to cocaine	1	581.1×	0.003	DRD3
positive regulation of mitotic nuclear division	1	543.6×	0.003	DRD3
positive regulation of cytokinesis	1	401.2×	0.004	DRD3
visual learning	1	306.4×	0.004	DRD3
learning	1	280.9×	0.005	DRD3
social behavior	1	271.8×	0.005	DRD3
negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	263.3×	0.005	DRD3
learning or memory	1	240.7×	0.005	DRD3
circadian regulation of gene expression	1	234.1×	0.005	DRD3

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
DRD3	CABERGOLINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DRD3	448	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CABERGOLINE	4	DRD3
APOMORPHINE	4	DRD3
HALOPERIDOL	4	DRD3
ROPINIROLE	4	DRD3
DOPAMINE	4	DRD3
CETIRIZINE	4	DRD3
AMIFOSTINE	4	DRD3
BEPRIDIL	4	DRD3
CANDESARTAN CILEXETIL	4	DRD3
CLOTRIMAZOLE	4	DRD3
CHOLECALCIFEROL	4	DRD3
SIMVASTATIN	4	DRD3
METHYSERGIDE	4	DRD3
OXAPROZIN	4	DRD3
PROPIVERINE	4	DRD3
ACETOPHENAZINE	4	DRD3
MESORIDAZINE	4	DRD3
VALPROIC ACID	4	DRD3
INDACATEROL	4	DRD3
IMIPRAMINE	4	DRD3
DROPERIDOL	4	DRD3
RIMONABANT	4	DRD3
ARIPIPRAZOLE	4	DRD3
AMOXAPINE	4	DRD3
IDARUBICIN	4	DRD3
DICYCLOMINE	4	DRD3
SAQUINAVIR	4	DRD3
PONATINIB	4	DRD3
DESLORATADINE	4	DRD3
DULOXETINE	4	DRD3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
DRD3	1,359	Binding:1088, Functional:262, ADMET:6, Unclassified:3

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
DRD3	1,359

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)
CABERGOLINE	4	DRD3
APOMORPHINE	4	DRD3
HALOPERIDOL	4	DRD3
ROPINIROLE	4	DRD3
DOPAMINE	4	DRD3
CETIRIZINE	4	DRD3
AMIFOSTINE	4	DRD3
BEPRIDIL	4	DRD3
CANDESARTAN CILEXETIL	4	DRD3
CLOTRIMAZOLE	4	DRD3
CHOLECALCIFEROL	4	DRD3
SIMVASTATIN	4	DRD3
METHYSERGIDE	4	DRD3
OXAPROZIN	4	DRD3
PROPIVERINE	4	DRD3
ACETOPHENAZINE	4	DRD3
MESORIDAZINE	4	DRD3
VALPROIC ACID	4	DRD3
INDACATEROL	4	DRD3
IMIPRAMINE	4	DRD3
DROPERIDOL	4	DRD3
RIMONABANT	4	DRD3
ARIPIPRAZOLE	4	DRD3
AMOXAPINE	4	DRD3
IDARUBICIN	4	DRD3
DICYCLOMINE	4	DRD3
SAQUINAVIR	4	DRD3
PONATINIB	4	DRD3
DESLORATADINE	4	DRD3
DULOXETINE	4	DRD3

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	DRD3
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: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01547481	Not specified	COMPLETED	MRI Study of Brain Activity in Healthy Adults and Individuals With Parkinsonism and Rapid Eye Movement Disorder.