Tremor, hereditary essential, 5
diseaseOn this page
Also known as essential tremor caused by mutation in TENM4essential tremor, hereditary, 5ETM5TENM4 essential tremortremor, hereditary essential, 5tremor, hereditary essential, type 5
Summary
Tremor, hereditary essential, 5 (MONDO:0014756) is a disease caused by TENM4 (GenCC Strong), with 1 cohort gene.
At a glance
- Causal gene: TENM4 (GenCC Strong)
- Cohort genes: 1
- ClinVar variants: 35
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | tremor, hereditary essential, 5 |
| Mondo ID | MONDO:0014756 |
| OMIM | 616736 |
| DOID | DOID:0111432 |
| UMLS | C4225223 |
| MedGen | 897748 |
| Is cancer (heuristic) | no |
Also known as: essential tremor caused by mutation in TENM4 · essential tremor, hereditary, 5 · ETM5 · TENM4 essential tremor · tremor, hereditary essential, 5 · tremor, hereditary essential, 5; ETM5 · tremor, hereditary essential, type 5
Data availability: 35 ClinVar variants · 3 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by body system or component › nervous system disorder › movement disorder › essential tremor › tremor, hereditary essential, 5
Related subtypes (5): tremor, hereditary essential, 1, tremor, hereditary essential, 2, tremor, hereditary essential, 3, tremor, hereditary essential, 4, 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
35 retrieved; paginated sample, class counts are floors:
25 uncertain significance, 4 conflicting classifications of pathogenicity, 4 benign, 2 pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1344494 | NM_001098816.3(TENM4):c.1262C>T (p.Pro421Leu) | TENM4 | Pathogenic | no assertion criteria provided |
| 219133 | NM_001098816.3(TENM4):c.4100C>A (p.Thr1367Asn) | TENM4 | Pathogenic | no assertion criteria provided |
| 1192521 | NM_001098816.3(TENM4):c.5287G>A (p.Gly1763Arg) | TENM4 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2437040 | NM_001098816.3(TENM4):c.277G>A (p.Gly93Arg) | TENM4 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 730091 | NM_001098816.3(TENM4):c.5545A>G (p.Thr1849Ala) | TENM4 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 806721 | NM_001098816.3(TENM4):c.4895G>A (p.Arg1632His) | TENM4 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1031826 | NM_001098816.3(TENM4):c.346G>A (p.Asp116Asn) | TENM4 | Uncertain significance | criteria provided, single submitter |
| 1319903 | NM_001098816.3(TENM4):c.4273G>A (p.Asp1425Asn) | TENM4 | Uncertain significance | criteria provided, single submitter |
| 1338998 | NM_001098816.3(TENM4):c.510G>A (p.Leu170=) | TENM4 | Uncertain significance | criteria provided, single submitter |
| 1711849 | NM_001098816.3(TENM4):c.1199C>A (p.Pro400His) | TENM4 | Uncertain significance | criteria provided, single submitter |
| 219134 | NM_001098816.3(TENM4):c.4324G>A (p.Ala1442Thr) | TENM4 | Uncertain significance | criteria provided, single submitter |
| 219135 | NM_001098816.3(TENM4):c.3412G>A (p.Val1138Met) | TENM4 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 2369553 | NM_001098816.3(TENM4):c.5419G>A (p.Gly1807Ser) | TENM4 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 2437035 | NM_001098816.3(TENM4):c.1471-9_1471-6del | TENM4 | Uncertain significance | criteria provided, single submitter |
| 2437036 | NM_001098816.3(TENM4):c.1520C>T (p.Ala507Val) | TENM4 | Uncertain significance | criteria provided, single submitter |
| 2437037 | NM_001098816.3(TENM4):c.1400A>G (p.Asn467Ser) | TENM4 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 2437038 | NM_001098816.3(TENM4):c.7939G>A (p.Val2647Ile) | TENM4 | Uncertain significance | criteria provided, single submitter |
| 2437039 | NM_001098816.3(TENM4):c.4981_4982del (p.Lys1661fs) | TENM4 | Uncertain significance | criteria provided, single submitter |
| 2437041 | NM_001098816.3(TENM4):c.553C>T (p.His185Tyr) | TENM4 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 2441966 | NM_001098816.3(TENM4):c.7557C>G (p.Ile2519Met) | TENM4 | Uncertain significance | criteria provided, single submitter |
| 2582627 | NM_001098816.3(TENM4):c.1126G>A (p.Glu376Lys) | TENM4 | Uncertain significance | criteria provided, single submitter |
| 3255559 | NM_001098816.3(TENM4):c.905G>A (p.Gly302Glu) | TENM4 | Uncertain significance | criteria provided, single submitter |
| 3341446 | NM_001098816.3(TENM4):c.2422G>A (p.Gly808Ser) | TENM4 | Uncertain significance | criteria provided, single submitter |
| 3892632 | NM_001098816.3(TENM4):c.4580A>G (p.Asp1527Gly) | TENM4 | Uncertain significance | criteria provided, single submitter |
| 3892633 | NM_001098816.3(TENM4):c.6571C>G (p.Arg2191Gly) | TENM4 | Uncertain significance | criteria provided, single submitter |
| 3892634 | NM_001098816.3(TENM4):c.7547G>A (p.Ser2516Asn) | TENM4 | Uncertain significance | criteria provided, single submitter |
| 4292652 | NM_001098816.3(TENM4):c.7451A>G (p.Asn2484Ser) | TENM4 | Uncertain significance | criteria provided, single submitter |
| 4540406 | NM_001098816.3(TENM4):c.4085A>G (p.Tyr1362Cys) | TENM4 | Uncertain significance | criteria provided, single submitter |
| 931031 | NM_001098816.3(TENM4):c.6668T>C (p.Leu2223Pro) | TENM4 | Uncertain significance | criteria provided, single submitter |
| 931802 | NM_001098816.3(TENM4):c.4681C>T (p.Arg1561Trp) | TENM4 | Uncertain significance | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 3 · 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 |
|---|---|---|---|---|
| TENM4 | Strong | Autosomal dominant | tremor, hereditary essential, 5 | 3 |
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 |
|---|---|---|---|---|---|
| TENM4 | HGNC:29945 | ENSG00000149256 | Q6N022 | Teneurin-4 | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| TENM4 | Teneurin-4 | Involved in neural development, regulating the establishment of proper connectivity within the nervous system. |
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) |
|---|---|---|---|---|
| TENM4 | Other/Unknown | no | EGF, YD, CarboxyPept-like_regulatory |
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 |
|---|---|
| ganglionic eminence | 1 |
| hair follicle | 1 |
| lateral nuclear group of thalamus | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| TENM4 | 228 | ubiquitous | marker | hair follicle, ganglionic eminence, lateral nuclear group of thalamus |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| TENM4 | 1,409 |
Structural data
PDB: 1 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| TENM4 | Q6N022 | 4 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).
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 |
|---|---|---|---|---|
| cardiac cell fate specification | 1 | 8426.0× | 0.001 | TENM4 |
| central nervous system myelin formation | 1 | 2407.4× | 0.002 | TENM4 |
| positive regulation of gastrulation | 1 | 2407.4× | 0.002 | TENM4 |
| gastrulation with mouth forming second | 1 | 936.2× | 0.002 | TENM4 |
| regulation of myelination | 1 | 887.0× | 0.002 | TENM4 |
| positive regulation of myelination | 1 | 766.0× | 0.002 | TENM4 |
| positive regulation of oligodendrocyte differentiation | 1 | 674.1× | 0.002 | TENM4 |
| cardiac muscle cell proliferation | 1 | 581.1× | 0.002 | TENM4 |
| synaptic membrane adhesion | 1 | 581.1× | 0.002 | TENM4 |
| neuron development | 1 | 255.3× | 0.004 | TENM4 |
| signal transduction | 1 | 16.1× | 0.062 | TENM4 |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1
Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| TENM4 | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
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 | TENM4 |
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) |
|---|---|---|
| TENM4 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.
Related Atlas pages
- Cohort genes: TENM4