TENM4

Summary

TENM4 (teneurin transmembrane protein 4, HGNC:29945) is a protein-coding gene on chromosome 11q14.1, encoding Teneurin-4 (Q6N022). Involved in neural development, regulating the establishment of proper connectivity within the nervous system.

The protein encoded by this gene plays a role in establishing proper neuronal connectivity during development. Defects in this gene have been associated with hereditary essential tremor-5.

Source: NCBI Gene 26011 — RefSeq curated summary.

At a glance

• Gene–disease (curated): tremor, hereditary essential, 5 (Strong, GenCC)
• GWAS associations: 30
• Clinical variants (ClinVar): 705 total — 2 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 14
• MANE Select transcript: NM_001098816

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29945
Approved symbol	TENM4
Name	teneurin transmembrane protein 4
Location	11q14.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1302, Ten-M4, TEN4, DOC4
Ensembl gene	ENSG00000149256
Ensembl biotype	protein_coding
OMIM	610084
Entrez	26011

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 5 protein_coding, 5 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000278550, ENST00000527736, ENST00000528688, ENST00000529798, ENST00000530738, ENST00000531583, ENST00000532654, ENST00000533013, ENST00000533038, ENST00000533074, ENST00000533525

RefSeq mRNA: 1 — MANE Select: NM_001098816 NM_001098816

CCDS: CCDS44688

Canonical transcript exons

ENST00000278550 — 34 exons

Exon	Start	End
ENSE00000989621	78661449	78661591
ENSE00000989622	78652829	78658816
ENSE00001151319	78672033	78672329
ENSE00001151429	78889785	78890020
ENSE00001469509	78720370	78720390
ENSE00001469521	78778602	78778628
ENSE00001507454	78668937	78670551
ENSE00001507456	78676152	78676387
ENSE00001507457	78688054	78688226
ENSE00001507459	78701526	78702403
ENSE00001507460	78708361	78708515
ENSE00001507462	78712482	78712714
ENSE00001507465	78722668	78722917
ENSE00001507466	78726079	78726222
ENSE00001507467	78729376	78729643
ENSE00001507468	78732316	78732577
ENSE00001507469	78738451	78738570
ENSE00001507470	78756805	78757021
ENSE00001507472	78786898	78787083
ENSE00001507473	78805292	78805492
ENSE00001507474	78812122	78812316
ENSE00001507475	78814294	78814395
ENSE00001507476	78854104	78854314
ENSE00001507477	78855964	78856178
ENSE00001507478	78862962	78863132
ENSE00001507483	79064738	79065007
ENSE00001704831	79440509	79441030
ENSE00001743330	79215808	79215909
ENSE00001788611	79148710	79148806
ENSE00001797679	79297488	79297543
ENSE00003465214	79069722	79070009
ENSE00003513999	78903268	78903523
ENSE00003694265	78891238	78891336
ENSE00003785125	78770992	78771138

Expression profiles

Bgee: expression breadth ubiquitous, 228 present calls, max score 92.03.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.2526 / max 182.6500, expressed in 943 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
121534	1.8366	644
121519	1.3281	319
121536	1.0659	542
121535	0.6785	366
121533	0.2844	107
121537	0.0592	14

Top tissues by expression

293 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
hair follicle	UBERON:0002073	92.03	gold quality
ganglionic eminence	UBERON:0004023	91.61	gold quality
lateral nuclear group of thalamus	UBERON:0002736	90.50	gold quality
embryo	UBERON:0000922	89.34	gold quality
sural nerve	UBERON:0015488	85.85	gold quality
ventricular zone	UBERON:0003053	84.73	gold quality
middle temporal gyrus	UBERON:0002771	83.77	gold quality
cortical plate	UBERON:0005343	83.15	gold quality
left ovary	UBERON:0002119	81.53	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.49	gold quality
Brodmann (1909) area 23	UBERON:0013554	80.44	gold quality
cranial nerve II	UBERON:0000941	80.38	gold quality
CA1 field of hippocampus	UBERON:0003881	80.25	gold quality
entorhinal cortex	UBERON:0002728	80.24	gold quality
ovary	UBERON:0000992	80.08	gold quality
stromal cell of endometrium	CL:0002255	79.83	gold quality
right ovary	UBERON:0002118	78.28	gold quality
gingival epithelium	UBERON:0001949	77.84	gold quality
cervix squamous epithelium	UBERON:0006922	77.60	silver quality
primary visual cortex	UBERON:0002436	76.74	gold quality
parietal lobe	UBERON:0001872	76.73	gold quality
postcentral gyrus	UBERON:0002581	76.59	gold quality
superior vestibular nucleus	UBERON:0007227	76.47	gold quality
pituitary gland	UBERON:0000007	76.42	gold quality
gingiva	UBERON:0001828	76.32	gold quality
corpus callosum	UBERON:0002336	76.16	gold quality
orbitofrontal cortex	UBERON:0004167	76.14	gold quality
occipital lobe	UBERON:0002021	76.05	gold quality
dorsal plus ventral thalamus	UBERON:0001897	75.82	gold quality
germinal epithelium of ovary	UBERON:0001304	75.76	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	41.95
E-MTAB-9388	yes	8.20
E-ANND-3	yes	6.96
E-MTAB-6058	no	57.76
E-MTAB-6075	no	35.02

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

191 targeting TENM4, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-12133	99.92	71.82	2006

Literature-anchored findings (GeneRIF, showing 8)

• An intronic variant in ODZ4 is being associated with bipolar disorder. (PMID:21926972)
• the ODZ4 risk variant influences reward processing in the amygdala (PMID:23611537)
• Data indicate that expression of several predicted chimeric genes and genes with disrupted exon structure including ALK, NBAS, FHIT, PTPRD and ODZ4 in neuroblastoma. (PMID:23991058)
• Ten-4 suppresses chondrogenic differentiation and regulates the expression and activation of the key molecules for chondrogenesis (PMID:24648313)
• Missense mutations in TENM4, a regulator of axon guidance and central myelination, cause essential tremor. Mutant proteins mislocalize in oligodendrocyte precursor cells. (PMID:26188006)
• This study demonstrated the TENM4 mutation associate with Essential tremor in Chinese. (PMID:27569844)
• TENM4 is not a cause for essential tremor in a Canadian population. (PMID:28158909)
• Han family with essential tremor caused by the P421L variant of the TENM4 gene in China. (PMID:36689009)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	tenm4	ENSDARG00000105088
mus_musculus	Tenm4	ENSMUSG00000048078
rattus_norvegicus	Tenm4	ENSRNOG00000011151
drosophila_melanogaster	Ten-m	FBGN0004449
drosophila_melanogaster	Ten-a	FBGN0267001
caenorhabditis_elegans		WBGENE00017892
caenorhabditis_elegans		WBGENE00018237

Paralogs (4): TENM1 (ENSG00000009694), NAGPA (ENSG00000103174), TENM2 (ENSG00000145934), TENM3 (ENSG00000218336)

Protein

Protein identifiers

Teneurin-4 — Q6N022 (reviewed: Q6N022)

Alternative names: Protein Odd Oz/ten-m homolog 4, Tenascin-M4, Teneurin transmembrane protein 4

All UniProt accessions (4): Q6N022, E9PPG4, H0YCJ4, H0YCW4

UniProt curated annotations — full annotation on UniProt →

Function. Involved in neural development, regulating the establishment of proper connectivity within the nervous system. Plays a role in the establishment of the anterior-posterior axis during gastrulation. Regulates the differentiation and cellular process formation of oligodendrocytes and myelination of small-diameter axons in the central nervous system (CNS). Promotes activation of focal adhesion kinase. May function as a cellular signal transducer.

Subunit / interactions. Homodimer; disulfide-linked. May also form heterodimer with either TENM1 or TENM2 or TENM3.

Subcellular location. Cell membrane. Cell projection. Nucleus. Cytoplasm.

Disease relevance. Tremor, hereditary essential 5 (ETM5) [MIM:616736] A common movement disorder mainly characterized by postural tremor of the arms. Head, legs, trunk, voice, jaw, and facial muscles may also be involved. The condition can be aggravated by emotions, hunger, fatigue and temperature extremes, and may cause a functional disability or even incapacitation. Inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. EGF-like domains 2 and 5 which have an odd number of cysteines might enable the formation of intermolecular disulfide bonds. Cytoplasmic proline-rich regions could serve as docking domains for intracellular SH3-containing proteins.

Similarity. Belongs to the tenascin family. Teneurin subfamily.

RefSeq proteins (1): NP_001092286* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000742	EGF	Domain
IPR006530	YD	Repeat
IPR008969	CarboxyPept-like_regulatory	Homologous_superfamily
IPR009471	Ten_N	Domain
IPR011042	6-blade_b-propeller_TolB-like	Homologous_superfamily
IPR022385	Rhs_assc_core	Domain
IPR028916	Tox-GHH_dom	Domain
IPR051216	Teneurin	Family
IPR056820	TEN_TTR-like	Domain
IPR056822	TEN_NHL	Domain
IPR056823	TEN-like_YD-shell	Domain
IPR057627	FN-plug_TEN1-4	Domain
IPR057629	Teneurin1-4_GBD	Domain

Pfam: PF06484, PF15636, PF23093, PF23538, PF24329, PF25020, PF25021, PF25023, PF25024

UniProt features (312 total): strand 151, helix 28, repeat 28, turn 23, disulfide bond 22, sequence variant 15, glycosylation site 12, domain 9, sequence conflict 8, compositionally biased region 6, region of interest 4, topological domain 2, modified residue 2, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
7PLP	X-RAY DIFFRACTION	1.4
7BAN	ELECTRON MICROSCOPY	2.7
7BAO	ELECTRON MICROSCOPY	2.7
7BAM	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

No AlphaFold model available for Q6N022 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 124, 178

Disulfide bonds (22): 566–576, 570–581, 583–592, 601–612, 614–623, 630–641, 635–646, 648–657, 662–673, 667–678, 680–689, 700–713, 715–724, 729–739, 733–744, 746–755, 760–770, 764–775, 777–786, 800–810 …

Glycosylation sites (12): 467, 940, 1259, 1609, 1705, 1741, 1799, 1884, 1985, 2188, 2328, 2646

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 257 (showing top): GOBP_MUSCLE_TISSUE_DEVELOPMENT, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GOBP_POSITIVE_REGULATION_OF_GLIAL_CELL_DIFFERENTIATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_GROWTH, GOBP_GLIAL_CELL_DEVELOPMENT, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_MYELINATION, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_MUSCLE_CELL_PROLIFERATION, GOBP_POSITIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_GASTRULATION_WITH_MOUTH_FORMING_SECOND, MORF_RAD51L3, MODULE_66, GOBP_CELL_CELL_ADHESION

GO Biological Process (12): gastrulation with mouth forming second (GO:0001702), signal transduction (GO:0007165), regulation of myelination (GO:0031641), positive regulation of myelination (GO:0031643), central nervous system myelin formation (GO:0032289), neuron development (GO:0048666), positive regulation of oligodendrocyte differentiation (GO:0048714), cardiac muscle cell proliferation (GO:0060038), cardiac cell fate specification (GO:0060912), synaptic membrane adhesion (GO:0099560), positive regulation of gastrulation (GO:2000543), cell differentiation (GO:0030154)

GO Molecular Function (5): protein homodimerization activity (GO:0042803), protein heterodimerization activity (GO:0046982), cell adhesion molecule binding (GO:0050839), protein binding (GO:0005515), identical protein binding (GO:0042802)

GO Cellular Component (7): nucleus (GO:0005634), cytoplasm (GO:0005737), plasma membrane (GO:0005886), neuron projection (GO:0043005), glutamatergic synapse (GO:0098978), membrane (GO:0016020), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
gastrulation	2
regulation of cellular process	2
myelination	2
protein dimerization activity	2
protein binding	2
cell communication	1
cellular process	1
signaling	1
cellular response to stimulus	1
regulation of nervous system development	1
regulation of myelination	1
positive regulation of nervous system process	1
positive regulation of cellular process	1
central nervous system myelination	1
myelin assembly	1
neuron differentiation	1
cell development	1
positive regulation of glial cell differentiation	1
oligodendrocyte differentiation	1
regulation of oligodendrocyte differentiation	1
striated muscle cell proliferation	1
cardiac muscle tissue growth	1
cell fate specification	1
cardiac cell fate commitment	1
synapse organization	1
cell-cell adhesion	1
regulation of gastrulation	1
positive regulation of embryonic development	1
cellular developmental process	1
identical protein binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
plasma membrane bounded cell projection	1
synapse	1

Protein interactions and networks

STRING

1348 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TENM4	OLFM1	Q99784	842
TENM4	ADGRL1	O94910	840
TENM4	ADGRL2	O95490	822
TENM4	ANK3	Q12955	722
TENM4	EGF	P01133	689
TENM4	ITIH3	Q06033	646
TENM4	TRANK1	O15050	644
TENM4	ADGRL3	Q9HAR2	643
TENM4	CACNA1C	Q13936	620
TENM4	NCAN	O14594	571
TENM4	CSMD1	Q96PZ7	527
TENM4	NKAIN3	Q8N8D7	526
TENM4	SYNE1	Q8NF91	519
TENM4	CACNB2	Q08289	510
TENM4	KCNS2	Q9ULS6	484

IntAct

37 interactions, top by confidence:

A	B	Type	Score
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
TENM4	DOCK2	psi-mi:“MI:0915”(physical association)	0.560
TENM4	ZNF587	psi-mi:“MI:0915”(physical association)	0.560
TENM4	PLSCR4	psi-mi:“MI:0915”(physical association)	0.560
TENM4	ZNF696	psi-mi:“MI:0915”(physical association)	0.560
LGALS4	TENM4	psi-mi:“MI:0915”(physical association)	0.560
TENM4	LCE3D	psi-mi:“MI:0915”(physical association)	0.560
HOXB9	TENM4	psi-mi:“MI:0915”(physical association)	0.560
TENM4	SHFL	psi-mi:“MI:0915”(physical association)	0.560
CLEC4A	SEMA7A	psi-mi:“MI:0914”(association)	0.530
DNAJC3	DEDD	psi-mi:“MI:0914”(association)	0.530
EVA1C	STK25	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
CAND1	GTPBP10	psi-mi:“MI:0914”(association)	0.350
EFNB2	TCAF2	psi-mi:“MI:0914”(association)	0.350
GOLPH3	FAM20B	psi-mi:“MI:0914”(association)	0.350
LMAN2L	NPC1	psi-mi:“MI:0914”(association)	0.350
SFTPC	CYTH3	psi-mi:“MI:0914”(association)	0.350
DISC1	TENM4	psi-mi:“MI:0915”(physical association)	0.000
DOCK2	TENM4	psi-mi:“MI:0915”(physical association)	0.000
ZNF587	TENM4	psi-mi:“MI:0915”(physical association)	0.000
PLSCR4	TENM4	psi-mi:“MI:0915”(physical association)	0.000
HOXB9	TENM4	psi-mi:“MI:0915”(physical association)	0.000
ZNF696	TENM4	psi-mi:“MI:0915”(physical association)	0.000
LGALS4	TENM4	psi-mi:“MI:0915”(physical association)	0.000
LCE3D	TENM4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (24): TENM4 (Two-hybrid), TENM4 (Two-hybrid), TENM4 (Two-hybrid), LCE3D (Two-hybrid), HOXB9 (Two-hybrid), LGALS4 (Two-hybrid), ZNF696 (Two-hybrid), ZNF587 (Two-hybrid), TENM4 (Affinity Capture-MS), TENM4 (Affinity Capture-MS), TENM4 (Affinity Capture-MS), TENM4 (Cross-Linking-MS (XL-MS)), TENM4 (Cross-Linking-MS (XL-MS)), TENM4 (Co-fractionation), TENM4 (Co-fractionation)

ESM2 similar proteins: A0A6I8RMG7, A7E2Z9, A8MWY0, B0S5G3, F1R520, L7VG99, O43556, O70258, O75829, O94985, P17404, P18564, P22413, P97259, P97675, Q08834, Q08B78, Q09328, Q13219, Q28IT1, Q29S03, Q3UHK6, Q3UZV7, Q4R5B1, Q5R9Q9, Q5RAP2, Q5RB89, Q6DDW2, Q6DYE8, Q6N022, Q6Q0N0, Q6YAT4, Q8BR76, Q8C1F4, Q8K1B9, Q8N6G5, Q8R4G6, Q8R4K8, Q8VDA1, Q99JH7

Diamond homologs: O61307, Q3UHK6, Q6N022, Q9DER5, Q9NT68, Q9P273, Q9R1K2, Q9UKZ4, Q9VYN8, Q9W6V6, Q9W7R3, Q9W7R4, Q9WTS4, Q9WTS5, Q9WTS6, Q7Z7M0, Q80Z71, G5EGQ6, Q55AP8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

705 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	532
Likely benign	64
Benign	43

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1344494	NM_001098816.3(TENM4):c.1262C>T (p.Pro421Leu)	Pathogenic
219133	NM_001098816.3(TENM4):c.4100C>A (p.Thr1367Asn)	Pathogenic
444266	NM_001098816.3(TENM4):c.2349del (p.Glu784fs)	Likely pathogenic

SpliceAI

7502 predictions. Top by Δscore:

Variant	Effect	Δscore
11:78658817:C:CC	acceptor_gain	1.0000
11:78661444:ATTAC:A	donor_loss	1.0000
11:78661445:TTACC:T	donor_loss	1.0000
11:78661446:TACCT:T	donor_loss	1.0000
11:78661447:A:AT	donor_loss	1.0000
11:78661448:CCTTG:C	donor_gain	1.0000
11:78668931:CCTTA:C	donor_loss	1.0000
11:78668932:CTTA:C	donor_loss	1.0000
11:78668933:TTAC:T	donor_loss	1.0000
11:78668934:TA:T	donor_loss	1.0000
11:78668935:ACCT:A	donor_loss	1.0000
11:78668936:C:CG	donor_loss	1.0000
11:78672062:T:TA	donor_gain	1.0000
11:78672063:C:A	donor_gain	1.0000
11:78676213:TC:T	donor_gain	1.0000
11:78676214:CC:C	donor_gain	1.0000
11:78676388:C:CC	acceptor_gain	1.0000
11:78701524:A:AC	donor_gain	1.0000
11:78701525:C:CG	donor_gain	1.0000
11:78701525:CT:C	donor_gain	1.0000
11:78708511:AATGC:A	acceptor_gain	1.0000
11:78708512:ATGC:A	acceptor_gain	1.0000
11:78708513:TGC:T	acceptor_gain	1.0000
11:78708514:GC:G	acceptor_gain	1.0000
11:78708515:CC:C	acceptor_gain	1.0000
11:78708516:C:CA	acceptor_loss	1.0000
11:78708516:C:CC	acceptor_gain	1.0000
11:78708517:T:C	acceptor_loss	1.0000
11:78708523:C:CT	acceptor_gain	1.0000
11:78708524:A:T	acceptor_gain	1.0000

AlphaMissense

18286 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:78661580:A:G	W2474R	1.000
11:78661580:A:T	W2474R	1.000
11:78669452:C:G	R2298P	1.000
11:78670001:C:T	G2115D	1.000
11:78676211:A:G	W1813R	1.000
11:78676211:A:T	W1813R	1.000
11:78701931:C:G	R1561P	1.000
11:78701937:C:G	R1559P	1.000
11:78722729:C:G	D1247H	1.000
11:78722819:A:G	C1217R	1.000
11:78722830:C:G	R1213T	1.000
11:78726222:A:T	V1136D	1.000
11:78771042:C:G	C830S	1.000
11:78771043:A:T	C830S	1.000
11:78771080:C:A	W817C	1.000
11:78771080:C:G	W817C	1.000
11:78771119:G:C	C804W	1.000
11:78771120:C:G	C804S	1.000
11:78771121:A:T	C804S	1.000
11:78786905:G:C	C786W	1.000
11:78786906:C:G	C786S	1.000
11:78786906:C:T	C786Y	1.000
11:78786907:A:T	C786S	1.000
11:78786920:C:A	W781C	1.000
11:78786920:C:G	W781C	1.000
11:78786922:A:G	W781R	1.000
11:78786922:A:T	W781R	1.000
11:78786960:C:T	G768E	1.000
11:78812211:C:G	C630S	1.000
11:78812212:A:G	C630R	1.000

dbSNP variants (sampled 300 via entrez): RS1000000221 (11:78844703 A>G), RS1000003231 (11:78919741 G>A), RS1000003400 (11:78706279 A>G), RS1000005659 (11:79313950 C>G), RS1000009511 (11:79208069 C>T), RS1000013656 (11:78886535 A>T), RS1000015002 (11:79185733 C>A,G), RS1000015563 (11:78750581 G>C), RS1000017237 (11:79421433 A>G), RS1000028902 (11:79225900 C>T), RS1000039967 (11:79388921 G>A), RS1000042947 (11:78788921 C>T), RS1000047486 (11:79383400 A>G), RS1000048543 (11:78959817 A>T), RS1000049816 (11:79038460 T>C)

Disease associations

OMIM: gene MIM:610084 | disease phenotypes: MIM:616736, MIM:618709, MIM:190300

GenCC curated gene-disease

Disease	Classification	Inheritance
tremor, hereditary essential, 5	Strong	Autosomal dominant

Mondo (5): tremor, hereditary essential, 5 (MONDO:0014756), neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures (MONDO:0032877), essential tremor (MONDO:0003233), retinal disorder (MONDO:0005283), cleft palate (MONDO:0016064)

Orphanet (2): Cleft palate (Orphanet:2014), NON RARE IN EUROPE: Hereditary essential tremor (Orphanet:862)

HPO phenotypes

14 total (14 of 14 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0002067	Bradykinesia
HP:0002080	Intention tremor
HP:0002174	Postural tremor
HP:0003584	Late onset
HP:0003596	Middle age onset
HP:0003621	Juvenile onset
HP:0003677	Slowly progressive
HP:0003829	Typified by incomplete penetrance
HP:0003831	Typified by age-related disease onset
HP:0011462	Young adult onset
HP:0011463	Childhood onset
HP:0030186	Kinetic tremor
HP:0031947	Tongue tremor

GWAS associations

30 associations (top):

Study	Trait	p-value
GCST001241_2	Bipolar disorder	4.000000e-08
GCST001762_497	Obesity-related traits	4.000000e-07
GCST001854_8	Retinopathy in non-diabetics	3.000000e-06
GCST001877_27	Autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia (combined)	4.000000e-08
GCST002385_3	Bipolar disorder	1.000000e-09
GCST002701_2	Verbal declarative memory	8.000000e-07
GCST002701_7	Verbal declarative memory	6.000000e-07
GCST002826_16	Urate levels (BMI interaction)	1.000000e-06
GCST003478_6	Hair greying	2.000000e-06
GCST003542_113	Night sleep phenotypes	4.000000e-06
GCST003671_7	Diastolic blood pressure	6.000000e-06
GCST003815_96	Late-onset Alzheimer’s disease	3.000000e-06
GCST004139_4	Bipolar disorder	3.000000e-09
GCST004747_22	Lung cancer in never smokers	1.000000e-06
GCST006013_5	Lactate dehydrogenase levels	5.000000e-09
GCST006224_6	Right lateral prefrontal cortical growth	8.000000e-06
GCST006248_8	Response to lurasidone in schizophrenia	2.000000e-06
GCST006865_12	Bipolar disorder	4.000000e-06
GCST007277_15	Tourette syndrome	5.000000e-06
GCST008103_56	Bipolar disorder	4.000000e-07
GCST008115_36	Bipolar I disorder	4.000000e-07
GCST008503_2	Fasting glucose change	9.000000e-07
GCST010219_14	Attention deficit hyperactivity disorder (inattention symptoms)	9.000000e-07
GCST010396_91	Gut microbiota (bacterial taxa, hurdle binary method)	1.000000e-06
GCST010818_23	Gut microbiota alpha diversity (PD_whole_tree index)	9.000000e-06
GCST011102_14	Bipolar disorder	2.000000e-08
GCST012189_1	Systolic blood pressure and diastolic blood pressure (bivariate analysis)	7.000000e-10
GCST012189_13	Systolic blood pressure and diastolic blood pressure (bivariate analysis)	2.000000e-06
GCST012465_36	Bipolar disorder	3.000000e-08
GCST90013407_66	Liver enzyme levels (gamma-glutamyl transferase)	5.000000e-30

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0004344	birth weight
EFO:0004874	memory performance
EFO:0006805	word list delayed recall measurement
EFO:0004340	body mass index
EFO:0004531	urate measurement
EFO:0006336	diastolic blood pressure
EFO:1001870	late-onset Alzheimers disease
EFO:0004808	L lactate dehydrogenase measurement
EFO:0009963	bipolar I disorder
EFO:0007874	gut microbiome measurement
EFO:0006335	systolic blood pressure
EFO:0004532	serum gamma-glutamyl transferase measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D002972	Cleft Palate	C05.500.460.185; C05.660.207.540.460.185; C07.320.440.185; C07.465.525.185; C07.650.500.460.185; C07.650.525.185; C16.131.621.207.540.460.185; C16.131.850.500.460.185; C16.131.850.525.185
D020329	Essential Tremor	C10.228.662.350
D012164	Retinal Diseases	C11.768

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs141531882	TENM4		0.00	0

CTD chemical–gene interactions

33 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	5
bisphenol A	affects cotreatment, increases expression, affects methylation	3
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	affects cotreatment, increases abundance, affects methylation, decreases expression	3
Estradiol	affects cotreatment, increases expression	3
Benzo(a)pyrene	affects methylation	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
benzo(e)pyrene	increases methylation	1
ferrous chloride	decreases expression	1
aflatoxin B2	increases methylation	1
hydroquinone	decreases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
bisphenol S	decreases methylation	1
NSC 689534	affects binding, decreases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Zoledronic Acid	increases expression	1
Fulvestrant	affects cotreatment, affects methylation, increases methylation	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Copper	affects binding, decreases expression	1
Doxorubicin	decreases expression	1
Methapyrilene	increases methylation	1
Progesterone	affects cotreatment, increases expression	1
Silicon Dioxide	decreases expression	1
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	1
Thiram	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_1400	MDA-MB-175-VII	Cancer cell line	Female
CVCL_A9SX	BL1391	Cancer cell line	Female

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00439699	PHASE4	COMPLETED	A Pilot Clinical Trial Of Memantine for Essential Tremor
NCT00584376	PHASE4	COMPLETED	Pregabalin (Lyrica) for the Treatment of Essential Tremor
NCT00998660	PHASE4	COMPLETED	RECHARGE Sub-Study to the Implantable Systems Performance Registry (ISPR)
NCT02111369	PHASE4	COMPLETED	Propranolol and Botulinum Toxin for Essential Vocal Tremor
NCT02495883	PHASE4	COMPLETED	Functional Imaging of Tremor Circuits and Mechanisms of Treatment Response
NCT01955135	PHASE4	COMPLETED	Anesthesia for Retinopathy of Prematurity
NCT02422056	PHASE4	COMPLETED	Acid Tranexamic Effectiveness in Reducing the Intraoperative Bleeding in Palatoplasty
NCT02915042	PHASE4	WITHDRAWN	Dexmedetomidine vs Placebo for Pediatric Cleft Palate Repair
NCT02953145	PHASE4	WITHDRAWN	The Use of Fibrin Sealant to Reduce Post Operative Pain in Cleft Palate Surgery
NCT03632044	PHASE4	ACTIVE_NOT_RECRUITING	Evaluation of Trigeminal Nerve Blockade
NCT06962306	PHASE4	RECRUITING	Optimizing Perioperative Analgesia to Lower Pain Following Cleft Palate Surgery
NCT00018564	PHASE3	COMPLETED	Novel Therapies for Essential Tremor
NCT00236496	PHASE3	COMPLETED	A Comparison of the Efficacy and Safety of Topiramate Versus Placebo in Treating Tremor of Unknown Cause.
NCT01441284	PHASE3	WITHDRAWN	Efficacy of Pramipexole Extended Release in the Treatment of Essential Tremor
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
NCT04265209	PHASE3	COMPLETED	[18F] LBT-999 PET Compared to [123I]-FP/CIT SPECT to Distinguish Between Parkinson’s Diseases and Essential Tremor
NCT06087276	PHASE3	ENROLLING_BY_INVITATION	Essential 3 - Decentralized, Phase 3 Study Evaluating the Safety and Efficacy of Ulixacaltamide in Essential Tremor (ET)
NCT00098319	PHASE3	COMPLETED	Oral Cleft Prevention Trial in Brazil
NCT00397917	PHASE3	COMPLETED	Oral Cleft Prevention Program
NCT04928352	PHASE3	RECRUITING	Nebulized Bupivacaine Analgesia for Cleft Palate Repair
NCT04928391	PHASE3	COMPLETED	A Single Bolus of Dexmedetomidine Versus Normal Saline in Postoperative Agitation
NCT00080366	PHASE2	COMPLETED	Octanol to Treat Essential Tremor
NCT00102596	PHASE2	COMPLETED	Clinical Trial Characterizing the Bioavailability of 1-Octanol in Adults With Ethanol-responsive Essential Tremor
NCT00223743	PHASE2	COMPLETED	A Safety/Efficacy Trial of Zonisamide for Essential Tremor
NCT00321087	PHASE2	TERMINATED	A Study of T2000 in Essential Tremor
NCT00598078	PHASE2	COMPLETED	Multiple-dose,Double-blind,Placebo-controlled Study of Sodium Oxybate in Patients With Essential Tremor
NCT00655278	PHASE2	TERMINATED	T2000 in Essential Tremor - Open Label Continuation
NCT01332695	PHASE2	COMPLETED	A Pilot Efficacy and Safety Study of ST101 in Essential Tremor
NCT02277106	PHASE2	COMPLETED	Evaluate SAGE-547 in Participants With Essential Tremor
NCT02551848	PHASE2	UNKNOWN	Kinematic-based BoNT-A Injections for Bilateral ET
NCT02668146	PHASE2	UNKNOWN	An Efficacy/Safety Study of Perampanel for Reducing Essential Tremor
NCT02978781	PHASE2	COMPLETED	A Study to Evaluate SAGE-217 in Participants With Essential Tremor
NCT03101241	PHASE2	COMPLETED	A Phase 2 RCT Study of CX-8998 for Essential Tremor
NCT03688685	PHASE2	COMPLETED	A Clinical Study to Evaluate CAD-1883 in Essential Tremor
NCT03780426	PHASE2	COMPLETED	tSMS in Essential Tremor
NCT04305275	PHASE2	COMPLETED	A Study to Evaluate the Efficacy, Safety, and Tolerability of SAGE-324 in Participants With Essential Tremor
NCT04727658	PHASE2	TERMINATED	Linac FRACtionated Radiosurgical THALamotomie in Tremors (FRACTHAL)
NCT04880616	PHASE2	COMPLETED	Safety, Efficacy, and Tolerability of NBI-827104 for the Treatment of Essential Tremor
NCT05021978	PHASE2	COMPLETED	A Clinical Trial of PRAX-944 in Participants With Essential Tremor
NCT05021991	PHASE2	COMPLETED	A Clinical Trial of 2 Doses of PRAX-944 in Participants With Essential Tremor