| Gene Symbol | Chromosome/Locus | Study/Year | Evidence Type | Key Finding | PMID where available |
|---|---|---|---|---|---|
| LINGO1 | 15q24.3 | deCODE GWAS; summarized in Kuhlenbäumer et al. / 2022 review | GWAS | First ET GWAS signal; rs9652490 reached genome-wide significance in combined analysis (reported p = 1.2 × 10⁻²⁹); LINGO1 remains one of the strongest replicated susceptibility signals in ET genetics (pqac-00000008, pqac-00000002) | 16650084, 16809426 (via OpenTargets pqac-00000000) |
| FUS | 16p11.2 | Exome sequencing family study; summarized in Kuhlenbäumer et al. / 2022 review | Exome / familial | Stop-gain variant c.868C>T (p.Gln290*) segregated with ET in a Franco-Canadian family; follow-up studies found limited additional mutations, so evidence supports rare familial contribution rather than common risk (pqac-00000008, pqac-00000001) | 19861302, 22863194 (pqac-00000000) |
| TENM4 | 11q14-q21 | Familial sequencing / prior linkage-supported candidate; OpenTargets | Familial / candidate gene | Missense mutations reported in familial ET; gene implicated in axon guidance and central myelination; currently among the strongest disease-target associations in OpenTargets for ET (pqac-00000001, pqac-00000011, pqac-00000000) | 26188006 (pqac-00000000) |
| STK32B | 4p16.2 | Common variant association in Chinese cohort / 2023; susceptibility locus in later GWAS meta-analyses | GWAS / replication | rs10937625 in/near STK32B associated with increased ET risk in eastern Chinese cohort (OR 1.50, 95% CI 1.17–1.93); STK32B also prioritized as a susceptibility locus in later meta-analysis (pqac-00000011, pqac-00000009) | Not provided in context |
| CA3 | 8q21.2 | Skuladottir et al. / 2024 | GWAS meta-analysis | Skuladottir 2024 meta-analysis (16,480 cases, 1,936,173 controls) identified 12 sequence variants at 11 loci and highlighted CA3 as a putative causal gene; protective lead variant correlated with lower CA3 expression/plasma carbonic anhydrase, nominating carbonic anhydrase biology as therapeutic target (pqac-00000051, pqac-00000052) | 38671141 |
| CPLX1 | 4p16.3 | Skuladottir et al. / 2024 | GWAS meta-analysis | Intronic risk variant implicated CPLX1, a regulator of neurotransmitter release; top cis-eQTL signal in blood strengthened candidacy as ET gene in Skuladottir 2024 (pqac-00000051, pqac-00000053) | 38671141 |
| BACE2 | 21q22.3 | Single-cell cerebellar eQTL / 2024; Ogonowski / 2025 | Single-cell eQTL integrated with GWAS / GWAS meta-analysis | ET-associated variants at the BACE2 locus were causally linked to BACE2 downregulation in cerebellar immature oligodendrocytes, suggesting oligodendrocyte vulnerability/demyelination; BACE2 also emerged as a causal gene in the 2025 meta-analysis (pqac-00000032, pqac-00000037, pqac-00000009) | 39024449 (OpenTargets pqac-00000000) |
| CACNA1A | 19p13.13 | Ogonowski et al. / 2025 | GWAS meta-analysis | Prioritized among significant loci in 2025 meta-analysis; biologically plausible ET gene because it encodes the P/Q-type calcium channel, linking ET risk to neuronal calcium homeostasis and cerebellar signaling (pqac-00000007, pqac-00000009) | Not provided in context |
| EHBP1 | 2p15 | Ogonowski et al. / 2025; Skuladottir et al. / 2024 | GWAS / replicated locus | Replicated previously reported ET locus in 2025 meta-analysis; nearby variation also raised OTX1 as a candidate effector in 2024 GWAS interpretation (pqac-00000007, pqac-00000053, pqac-00000000) | 38671141 (OpenTargets evidence set, pqac-00000000) |
| SLC1A2 | 11p13-p12 | Prior GWAS; summarized in Kuhlenbäumer / 2022 review | GWAS | Encodes major glial glutamate transporter EAAT2; achieved genome-wide significance in earlier ET GWAS work and supports glutamatergic involvement in ET pathophysiology (pqac-00000008, pqac-00000012) | Not provided in context |
| CALN1 | 7q11.23 | OpenTargets / linked to recent ET genetics | GWAS-linked target prioritization | CALN1 is listed among current ET-associated targets in OpenTargets with evidence derived from recent ET genetic studies, supporting calcium-signaling-related mechanisms (pqac-00000000) | 39024449 (pqac-00000000) |
| PPM1J | 1q32.1 | Ogonowski et al. / 2025; OpenTargets | GWAS meta-analysis | Identified among key genes/loci in 2025 GWAS meta-analysis; encodes Mg²⁺/Mn²⁺-dependent phosphatase and contributes to expanded common-variant architecture of ET (pqac-00000007, pqac-00000000) | 39024449 (pqac-00000000) |
| PIK3R1 | 5q13.1 | OpenTargets / recent ET genetic studies | GWAS-linked target prioritization | Appears among ET-associated targets in OpenTargets based on recent human genetic evidence, suggesting PI3K signaling may contribute to ET susceptibility (pqac-00000000) | 38671141, 39024449 (pqac-00000000) |
| NOTCH2NLC | 1q21.2 | Repeat-expansion disorder overlap studies; OpenTargets | Repeat expansion / syndromic overlap | Associated mainly with hereditary essential tremor subtype/NIID-spectrum overlap rather than typical complex ET; illustrates diagnostic overlap between clinically defined ET and repeat-expansion disorders (pqac-00000000, pqac-00000001) | 32333675 (pqac-00000000) |
| PPARGC1A | 4p15.1 | Ogonowski et al. / 2025 | GWAS meta-analysis | Prioritized in 2025 meta-analysis; implicates mitochondrial biogenesis/energy metabolism (PGC-1α biology) in ET genetic risk architecture (pqac-00000007) | Not provided in context |
| **ET GWAS summary** | Multiple loci | **Skuladottir 2024** | GWAS meta-analysis | **16,480 ET cases and 1,936,173 controls; 12 sequence variants at 11 loci (8 novel); ~4.4% of genetic variance explained; putative causal genes included CA3 and CPLX1; enrichment in dopaminergic and GABAergic neurons; positive genetic correlation with Parkinson's disease (rg = 0.28)** (pqac-00000051, pqac-00000052) | 38671141 |
| **ET GWAS summary** | Multiple loci | **Ogonowski 2025** | GWAS meta-analysis (preprint) | **20,268 ET cases and 723,761 controls; 50 independent genome-wide significant loci, 47 novel; SNP-based heritability 24% (18.5% liability scale); implicated BACE2, CACNA1A, PPARGC1A, PPM1J and cerebellar/ventral diencephalic morphometry** (pqac-00000006, pqac-00000007, pqac-00000010) | Not yet available in context |
| **OpenTargets ET disease node** | MONDO_0003233 | OpenTargets (current database snapshot) | Integrated genetics / target prioritization | **ET is mapped to MONDO_0003233; top associated targets include TENM4, FUS, NOTCH2NLC, BACE2, DRD3, SCN4A, CALN1, PPM1J, PIK3R1, EHBP1, and SLC24A2** (pqac-00000000) | Database context only |


*Table: This table summarizes major ET-associated genes across GWAS, familial/exome, and repeat-expansion studies, with emphasis on the 2024 and 2025 large-scale genetic analyses. It is useful for linking named candidate genes to their study context, evidence type, and current level of support.*