TENM2

Summary

TENM2 (teneurin transmembrane protein 2, HGNC:29943) is a protein-coding gene on chromosome 5q34, encoding Teneurin-2 (Q9NT68). Involved in neural development, regulating the establishment of proper connectivity within the nervous system.

Enables cell adhesion molecule binding activity and signaling receptor binding activity. Involved in retrograde trans-synaptic signaling by trans-synaptic protein complex. Located in cell-cell junction and plasma membrane.

Source: NCBI Gene 57451 — RefSeq curated summary.

At a glance

• GWAS associations: 40
• Clinical variants (ClinVar): 434 total
• Phenotypes (HPO): 2
• MANE Select transcript: NM_001395460

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29943
Approved symbol	TENM2
Name	teneurin transmembrane protein 2
Location	5q34
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1127, Ten-M2, TEN2
Ensembl gene	ENSG00000145934
Ensembl biotype	protein_coding
OMIM	610119
Entrez	57451

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 6 protein_coding, 5 protein_coding_CDS_not_defined, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000517586, ENST00000517941, ENST00000518659, ENST00000518693, ENST00000519204, ENST00000520394, ENST00000521126, ENST00000522488, ENST00000695884, ENST00000695885, ENST00000695886, ENST00000695887, ENST00000695888, ENST00000695961, ENST00000695962

RefSeq mRNA: 5 — MANE Select: NM_001395460 NM_001080428, NM_001122679, NM_001368145, NM_001368146, NM_001395460

CCDS: CCDS83040, CCDS93818, CCDS93819

Canonical transcript exons

ENST00000518659 — 31 exons

Exon	Start	End
ENSE00000769040	168124850	168125050
ENSE00001026033	168216768	168216922
ENSE00001026037	168244420	168244716
ENSE00001026038	168218125	168218999
ENSE00001026040	168203689	168203832
ENSE00001026041	168226088	168226263
ENSE00001026044	168199864	168200131
ENSE00001026046	168246757	168248371
ENSE00001026050	168215040	168215272
ENSE00001084271	168260283	168260413
ENSE00001084276	168162611	168162757
ENSE00001084281	168190337	168190547
ENSE00001308822	168195176	168195295
ENSE00001328175	168198853	168199114
ENSE00001473888	168098026	168098127
ENSE00001473889	168090574	168090769
ENSE00001473890	168062060	168062265
ENSE00001473891	168047427	168047549
ENSE00001504357	168211734	168211754
ENSE00001504358	168118292	168118486
ENSE00002099756	168262049	168264157
ENSE00002104612	168126754	168126966
ENSE00002110576	167375198	167375473
ENSE00002126960	167284764	167285063
ENSE00002491449	168204372	168204621
ENSE00003467751	168227895	168228130
ENSE00003500286	167992944	167993182
ENSE00003593717	167952588	167952822
ENSE00003624937	167875986	167876195
ENSE00003965346	166979029	166979523
ENSE00003965359	167073242	167073356

Expression profiles

Bgee: expression breadth ubiquitous, 207 present calls, max score 99.44.

FANTOM5 (CAGE): breadth broad, TPM avg 12.1836 / max 1320.5325, expressed in 774 samples.

FANTOM5 promoters (30 alternative TSS)

Promoter ID	TPM avg	Samples expressed
60025	3.8804	304
60017	3.1460	441
60012	1.0446	205
60023	1.0256	184
60057	0.7022	94
60011	0.3637	81
60013	0.2607	82
60016	0.2453	89
60014	0.2214	59
60010	0.1796	73

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	99.44	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.35	gold quality
middle temporal gyrus	UBERON:0002771	97.92	gold quality
endothelial cell	CL:0000115	97.83	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.42	gold quality
myocardium	UBERON:0002349	96.56	gold quality
dorsal root ganglion	UBERON:0000044	96.16	gold quality
heart right ventricle	UBERON:0002080	96.05	gold quality
buccal mucosa cell	CL:0002336	95.42	gold quality
gingival epithelium	UBERON:0001949	94.60	gold quality
sural nerve	UBERON:0015488	93.86	gold quality
trigeminal ganglion	UBERON:0001675	93.17	gold quality
postcentral gyrus	UBERON:0002581	91.84	gold quality
gingiva	UBERON:0001828	91.83	gold quality
primary visual cortex	UBERON:0002436	91.74	gold quality
occipital lobe	UBERON:0002021	91.73	gold quality
entorhinal cortex	UBERON:0002728	91.70	gold quality
parietal lobe	UBERON:0001872	91.34	gold quality
cardiac ventricle	UBERON:0002082	91.32	gold quality
lateral nuclear group of thalamus	UBERON:0002736	91.22	gold quality
heart left ventricle	UBERON:0002084	91.13	gold quality
superior frontal gyrus	UBERON:0002661	90.78	gold quality
cortical plate	UBERON:0005343	88.44	gold quality
cardiac atrium	UBERON:0002081	87.72	gold quality
right atrium auricular region	UBERON:0006631	86.94	gold quality
Brodmann (1909) area 46	UBERON:0006483	86.69	gold quality
upper arm skin	UBERON:0004263	86.01	gold quality
heart	UBERON:0000948	85.52	gold quality
apex of heart	UBERON:0002098	85.12	gold quality
vena cava	UBERON:0004087	84.55	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-GEOD-180759	yes	6074.54
E-CURD-53	yes	245.09
E-HCAD-35	yes	92.91
E-HCAD-25	yes	77.08
E-CURD-119	yes	31.20
E-GEOD-137537	yes	7.88
E-ANND-3	yes	7.17
E-GEOD-81547	yes	4.89
E-MTAB-7249	yes	3.27
E-MTAB-11268	no	953.53
E-GEOD-83139	no	2.71

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

103 targeting TENM2, 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-6867-5P	100.00	82.21	3464
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-219A-5P	99.91	73.36	735

Literature-anchored findings (GeneRIF, showing 4)

• intracellular domain of teneurin-2 has a nuclear function and role in repressing zic-1-mediated transcription (PMID:12783990)
• Gene rearrangements of ODZ2 is associated with mucosa-associated lymphoid tissue lymphoma. (PMID:18927281)
• TENM2 knockdown induces both UCP1 mRNA and protein expression upon adipogenic differentiation without affecting mitochondrial mass. (PMID:28088466)
• These findings reveal a novel mechanism of axonal pathfinding, whereby latrophilin-1 and Lasso mediate both short-range interaction that supports synaptogenesis, and long-range signaling that induces axonal attraction. (PMID:30457553)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	tenm2b	ENSDARG00000011171
danio_rerio	tenm2a	ENSDARG00000037122
danio_rerio	tenm2b	ENSDARG00000090676
mus_musculus	Tenm2	ENSMUSG00000049336
rattus_norvegicus	Tenm2	ENSRNOG00000027341
drosophila_melanogaster	Ten-m	FBGN0004449
drosophila_melanogaster	Ten-a	FBGN0267001
caenorhabditis_elegans		WBGENE00017892
caenorhabditis_elegans		WBGENE00018237

Paralogs (4): TENM1 (ENSG00000009694), NAGPA (ENSG00000103174), TENM4 (ENSG00000149256), TENM3 (ENSG00000218336)

Protein

Protein identifiers

Teneurin-2 — Q9NT68 (reviewed: Q9NT68)

Alternative names: Protein Odd Oz/ten-m homolog 2, Tenascin-M2, Teneurin transmembrane protein 2

All UniProt accessions (7): A0A8Q3SI53, A0A8Q3SI97, A0A8Q3SIA3, A0A8Q3SIB5, F8VNQ3, G3V106, Q9NT68

UniProt curated annotations — full annotation on UniProt →

Function. Involved in neural development, regulating the establishment of proper connectivity within the nervous system. Acts as a ligand of the ADGRL1 and ADGRL3 receptors that are expressed at the surface of adjacent cells. Promotes the formation of filopodia and enlarged growth cone in neuronal cells. Mediates axon guidance and homophilic and heterophilic cell-cell adhesion. May function as a cellular signal transducer. Acts as a ligand of the ADGRL1 receptor. Mediates axon guidance and heterophilic cell-cell adhesion. Induces gene transcription inhibition.

Subunit / interactions. Homodimer; disulfide-linked. Heterodimer with either TENM1 or TENM3. May also form heterodimer with TENM4. Isoform 2 (C-terminal globular domain) interacts with ADGRL1 isoform 2.

Subcellular location. Cell membrane. Presynaptic cell membrane. Postsynaptic cell membrane. Endoplasmic reticulum. Golgi apparatus. Synapse. Cell projection. Dendritic spine. Filopodium. Growth cone Cell membrane Nucleus. PML body.

Tissue specificity. Highly expressed in heart, followed by brain, liver, kidney and fetal brain and weakly expressed in lung and testis. No expression was detected in skeletal muscle, pancreas, spleen, ovary and fetal liver.

Post-translational modifications. Derives from the membrane form by proteolytic processing. Derives from the plasma membrane form by proteolytic cleavage and translocates to the nucleus. Homophilic binding of the C-terminal extracellular domain stimulates its proteolytic cleavage and release in the cytoplasmic. Is subjected to rapid degradation by the proteasome pathway.

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.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NT68-1	1	yes
Q9NT68-2	2, Lasso, LPH1-associated synaptic surface organizer

RefSeq proteins (5): NP_001073897, NP_001116151, NP_001355074, NP_001355075, NP_001382389* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000742	EGF	Domain
IPR001881	EGF-like_Ca-bd_dom	Domain
IPR006530	YD	Repeat
IPR008969	CarboxyPept-like_regulatory	Homologous_superfamily
IPR009471	Ten_N	Domain
IPR011042	6-blade_b-propeller_TolB-like	Homologous_superfamily
IPR011044	Quino_amine_DH_bsu	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 (293 total): strand 157, repeat 28, disulfide bond 22, turn 19, helix 19, glycosylation site 15, domain 9, compositionally biased region 5, modified residue 4, splice variant 4, chain 3, topological domain 2, sequence variant 2, transmembrane region 1, region of interest 1, site 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6VHH	ELECTRON MICROSCOPY	2.97
6CMX	ELECTRON MICROSCOPY	3.1

Predicted structure (AlphaFold)

No AlphaFold model available for Q9NT68 — 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.

Catalytic / active sites (1): 528–529 (cleavage)

Post-translational modifications (4): 90, 124, 155, 157

Disulfide bonds (22): 576–586, 580–591, 593–602, 611–622, 624–633, 640–651, 645–656, 658–667, 672–683, 677–688, 690–699, 710–723, 725–734, 739–749, 743–754, 756–765, 770–780, 774–785, 787–796, 810–820 …

Glycosylation sites (15): 443, 482, 925, 948, 1267, 1616, 1712, 1749, 1773, 1807, 1892, 1993, 2197, 2337, 2648

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 154 (showing top): GOBP_NEUROGENESIS, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_CELL_CELL_SIGNALING, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, GOBP_CELL_CELL_ADHESION, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, MARTINEZ_RB1_TARGETS_DN, GOBP_POSITIVE_REGULATION_OF_FILOPODIUM_ASSEMBLY, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN, GOBP_SYNAPTIC_SIGNALING, CHIANG_LIVER_CANCER_SUBCLASS_INTERFERON_DN, GOCC_NEURON_PROJECTION, GOBP_CELL_PROJECTION_ORGANIZATION, CUI_TCF21_TARGETS_2_DN

GO Biological Process (7): negative regulation of transcription by RNA polymerase II (GO:0000122), signal transduction (GO:0007165), neuron development (GO:0048666), positive regulation of filopodium assembly (GO:0051491), cell-cell adhesion (GO:0098609), retrograde trans-synaptic signaling by trans-synaptic protein complex (GO:0098942), cell adhesion (GO:0007155)

GO Molecular Function (5): signaling receptor binding (GO:0005102), calcium ion binding (GO:0005509), protein homodimerization activity (GO:0042803), protein heterodimerization activity (GO:0046982), cell adhesion molecule binding (GO:0050839)

GO Cellular Component (17): nucleus (GO:0005634), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), PML body (GO:0016605), cell junction (GO:0030054), filopodium (GO:0030175), dendrite (GO:0030425), growth cone (GO:0030426), presynaptic membrane (GO:0042734), neuron projection (GO:0043005), dendritic spine (GO:0043197), synapse (GO:0045202), postsynaptic membrane (GO:0045211), membrane (GO:0016020), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	3
cellular anatomical structure	3
cellular process	2
protein binding	2
protein dimerization activity	2
cytoplasm	2
endomembrane system	2
synaptic membrane	2
postsynapse	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
neuron differentiation	1
cell development	1
filopodium assembly	1
regulation of filopodium assembly	1
positive regulation of plasma membrane bounded cell projection assembly	1
cell adhesion	1
retrograde trans-synaptic signaling	1
trans-synaptic signaling by trans-synaptic complex	1
metal ion binding	1
identical protein binding	1
membrane	1
cell periphery	1
anchoring junction	1
nuclear body	1
actin-based cell projection	1
neuron projection	1
dendritic tree	1
site of polarized growth	1
distal axon	1
presynapse	1
plasma membrane bounded cell projection	1
dendrite	1
neuron spine	1
cell junction	1

Protein interactions and networks

STRING

1333 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TENM2	ADGRL1	O94910	971
TENM2	ADGRL2	O95490	943
TENM2	ADGRL3	Q9HAR2	896
TENM2	FLRT3	Q9NZU0	871
TENM2	ZIC1	Q15915	605
TENM2	EGF	P01133	541
TENM2	NXPE1	Q8N323	501
TENM2	LCT	P09848	478
TENM2	CNTN6	Q9UQ52	478
TENM2	ROBO2	Q9HCK4	449
TENM2	A0A3B3IT14	A0A3B3IT14	444
TENM2	FOXP1	Q9H334	444
TENM2	NRXN1	Q9ULB1	430
TENM2	FRS3	O43559	428
TENM2	ARHGAP9	Q9BRR9	428

IntAct

24 interactions, top by confidence:

A	B	Type	Score
TSPAN15	ADAM10	psi-mi:“MI:0914”(association)	0.840
TSPAN5	ADAM10	psi-mi:“MI:0914”(association)	0.800
CD9	ADAM10	psi-mi:“MI:0914”(association)	0.750
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
CLEC4A	SEMA7A	psi-mi:“MI:0914”(association)	0.530
CTLA4	B4GALT5	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
DCAF4	IGLL5	psi-mi:“MI:0914”(association)	0.350
MYC		psi-mi:“MI:0914”(association)	0.350
CLGN	TMEM131L	psi-mi:“MI:0914”(association)	0.350
EFNB1	IPO5	psi-mi:“MI:0914”(association)	0.350
EFNB2	TCAF2	psi-mi:“MI:0914”(association)	0.350
LMAN2L	NPC1	psi-mi:“MI:0914”(association)	0.350
PACC1	IPO5	psi-mi:“MI:0914”(association)	0.350
PCDHGB5	TMEM223	psi-mi:“MI:0914”(association)	0.350
SFTPC	CYTH3	psi-mi:“MI:0914”(association)	0.350
TMEM169	PTGES3L-AARSD1	psi-mi:“MI:0914”(association)	0.350
LAMP1	PIPSL	psi-mi:“MI:2364”(proximity)	0.270
DISC1	TENM2	psi-mi:“MI:0915”(physical association)	0.000

ESM2 similar proteins: A0A0R4IKU3, A0A8M9PFP2, A1A5Y0, A2A863, A2VCU8, A5A6L1, B0S5G3, L7VG99, O00622, O08841, O35118, O42493, O93512, P08163, P08833, P16042, P16144, P17668, P18406, Q07663, Q0VCN6, Q13753, Q501P1, Q53RD9, Q5R9Q9, Q61220, Q61592, Q64632, Q6DDW2, Q7T3Q2, Q7ZV46, Q7ZXL5, Q8R4Y4, Q8R553, Q8VDA1, Q91166, Q91167, Q91713, Q99JH7, Q9BQT9

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	394
Likely benign	16
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

2054 predictions. Top by Δscore:

Variant	Effect	Δscore
5:167285038:G:GT	donor_gain	1.0000
5:167285046:A:G	donor_gain	1.0000
5:167284999:G:GT	donor_gain	0.9900
5:167285046:A:AG	donor_gain	0.9900
5:167285059:ACAAG:A	donor_loss	0.9900
5:167285060:CAAGG:C	donor_loss	0.9900
5:167285062:AGGT:A	donor_loss	0.9900
5:167285063:GGT:G	donor_loss	0.9900
5:167285065:T:A	donor_loss	0.9900
5:167375469:GAACG:G	donor_gain	0.9900
5:167406695:A:G	donor_gain	0.9900
5:167418623:GAAGA:G	donor_gain	0.9900
5:167401433:GCCA:G	donor_gain	0.9800
5:167406693:GTA:G	donor_gain	0.9800
5:167406694:TAT:T	donor_gain	0.9800
5:167406695:ATA:A	donor_gain	0.9800
5:167418627:A:G	donor_gain	0.9800
5:167426053:T:A	acceptor_gain	0.9800
5:167346376:G:T	donor_gain	0.9700
5:167375191:A:AG	acceptor_gain	0.9700
5:167375192:CCCTA:C	acceptor_loss	0.9700
5:167375193:CCTA:C	acceptor_loss	0.9700
5:167375194:CTA:C	acceptor_loss	0.9700
5:167375195:TAGG:T	acceptor_loss	0.9700
5:167375196:AGG:A	acceptor_loss	0.9700
5:167375197:G:GA	acceptor_loss	0.9700
5:167375470:AACG:A	donor_loss	0.9700
5:167375471:ACGG:A	donor_loss	0.9700
5:167375472:CG:C	donor_loss	0.9700
5:167375473:GG:G	donor_loss	0.9700

AlphaMissense

18334 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:168062192:T:C	F481S	1.000
5:168062230:T:G	Y494D	1.000
5:168062237:G:T	R496I	1.000
5:168062252:C:A	P501Q	1.000
5:168062252:C:G	P501R	1.000
5:168090703:T:A	W549R	1.000
5:168090703:T:C	W549R	1.000
5:168098054:C:G	C580W	1.000
5:168098065:G:A	G584D	1.000
5:168098120:T:G	C602W	1.000
5:168118309:T:A	C611S	1.000
5:168118309:T:C	C611R	1.000
5:168118310:G:A	C611Y	1.000
5:168118310:G:C	C611S	1.000
5:168118311:C:G	C611W	1.000
5:168118322:G:A	G615E	1.000
5:168118342:T:A	C622S	1.000
5:168118343:G:C	C622S	1.000
5:168118348:T:A	C624S	1.000
5:168118349:G:C	C624S	1.000
5:168118375:T:A	C633S	1.000
5:168118375:T:C	C633R	1.000
5:168118376:G:C	C633S	1.000
5:168118377:C:G	C633W	1.000
5:168126824:G:C	W760C	1.000
5:168126824:G:T	W760C	1.000
5:168162706:T:A	C840S	1.000
5:168162707:G:C	C840S	1.000
5:168198861:T:C	L970P	1.000
5:168199918:A:C	S1073R	1.000

dbSNP variants (sampled 300 via entrez): RS1000001159 (5:167974430 G>A,T), RS1000001570 (5:167824305 T>C,G), RS1000001761 (5:167951543 G>A), RS1000003976 (5:167683572 C>T), RS1000008268 (5:167071508 A>G,T), RS1000010100 (5:167280952 G>A), RS1000010756 (5:167070184 C>T), RS1000012267 (5:167478549 G>A), RS1000014337 (5:167754186 G>C), RS1000021941 (5:167782878 C>T), RS1000022213 (5:167865917 G>A,T), RS1000023335 (5:167527061 C>T), RS1000025670 (5:166980073 C>A), RS1000029503 (5:167235180 C>A), RS1000030745 (5:167485738 G>T)

Disease associations

OMIM: gene MIM:610119 | disease phenotypes:

GenCC curated gene-disease

Mondo (3): neurodevelopmental disorder (MONDO:0700092), esophageal atresia (MONDO:0001044), pyloric stenosis (MONDO:0001561)

Orphanet (0):

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0002032	Esophageal atresia
HP:0002021	Pyloric stenosis

GWAS associations

40 associations (top):

Study	Trait	p-value
GCST001017_12	Diabetic retinopathy	1.000000e-06
GCST001374_5	Uric acid levels	5.000000e-06
GCST001532_5	Immune response to smallpox vaccine (IL-6)	5.000000e-07
GCST001588_7	Periodontal microbiota	1.000000e-06
GCST002541_18	Menarche (age at onset)	1.000000e-11
GCST002571_2	Body mass index	3.000000e-07
GCST002955_7	Forced expiratory volume in 1 second (occupational environmental exposures interaction)	1.000000e-07
GCST003075_92	Cognitive decline rate in late mild cognitive impairment	7.000000e-07
GCST003264_1595	Post bronchodilator FEV1/FVC ratio	7.000000e-09
GCST003542_122	Night sleep phenotypes	5.000000e-06
GCST003783_3	Multiple system atrophy (pathologically confirmed)	4.000000e-06
GCST003880_6	Schizophrenia	6.000000e-07
GCST003963_2	Possible neuropathic pain in post total joint replacement surgery for osteoarthritis	5.000000e-06
GCST004691_7	Huntington’s disease progression	3.000000e-06
GCST005839_31	Depression	7.000000e-09
GCST006285_2	Response to aripiprazole in schizophrenia	4.000000e-07
GCST006618_1	Uterine fibroid size (maximum dimension)	2.000000e-09
GCST006922_13	Regular attendance at a religious group	5.000000e-10
GCST007160_12	Refractive astigmatism	7.000000e-06
GCST007277_8	Tourette syndrome	2.000000e-06
GCST007323_4	Risk-taking tendency (4-domain principal component model)	4.000000e-09
GCST007326_69	Number of sexual partners	1.000000e-08
GCST007327_217	Smoking status (ever vs never smokers)	8.000000e-14
GCST007576_420	Chronotype	2.000000e-08
GCST007576_63	Chronotype	5.000000e-10
GCST007603_37	Smoking initiation	6.000000e-09
GCST008550_5	Mental health study participation (completed survey)	5.000000e-09
GCST008757_38	Alcohol consumption	3.000000e-09
GCST008810_40	Smoking initiation (ever regular vs never regular)	1.000000e-09
GCST009600_54	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	7.000000e-09

EFO canonical traits (24, from GWAS)

EFO ID	Trait name
EFO:0004761	uric acid measurement
EFO:0004645	response to vaccine
EFO:0004873	cytokine measurement
EFO:0004703	age at menarche
EFO:0004340	body mass index
EFO:0004314	forced expiratory volume
EFO:0006994	response to gases and fumes exposure
EFO:0007710	cognitive decline measurement
EFO:0004713	FEV/FVC ratio
EFO:0005762	neuropathic pain
EFO:0008336	disease progression measurement
EFO:0009410	uterine fibroid measurement
EFO:0009592	social interaction measurement
EFO:0008579	risk-taking behaviour
EFO:0004318	smoking behavior
EFO:0008328	chronotype measurement
EFO:0005670	smoking initiation
EFO:0010130	health study participation
EFO:0007874	gut microbiome measurement
EFO:0005665	white matter hyperintensity measurement
EFO:0005674	white matter microstructure measurement
EFO:0004531	urate measurement
EFO:0009749	age at first sexual intercourse measurement
EFO:0004532	serum gamma-glutamyl transferase measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D004933	Esophageal Atresia	C06.198.330; C06.405.117.260; C16.131.314.330
D017219	Gastric Outlet Obstruction	C06.405.748.340
D065886	Neurodevelopmental Disorders	F03.625
D011707	Pyloric Stenosis	C06.405.748.340.690

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
rs17495520	TENM2	3	0.00	1	salbutamol

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, affects cotreatment, increases expression	7
bisphenol A	increases expression, increases methylation, affects cotreatment, affects methylation, decreases expression	3
trichostatin A	affects cotreatment, increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	3
Aflatoxin B1	decreases expression, increases methylation	3
sodium arsenite	affects methylation, affects cotreatment, decreases expression, increases abundance	2
(+)-JQ1 compound	decreases expression	2
Panobinostat	affects cotreatment, increases expression	2
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Estradiol	affects expression, affects cotreatment, increases expression	2
Formaldehyde	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
methylmercuric chloride	decreases expression	1
methyleugenol	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
senecionine	decreases expression	1
senkirkine	decreases expression	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
heliotrine	decreases expression	1
zinc chromate	increases abundance, decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	increases expression	1
aflatoxin B2	decreases methylation	1
chromium hexavalent ion	decreases expression, increases abundance	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	increases expression, affects cotreatment	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT00556283	PHASE4	COMPLETED	RCT: STARR vs Biofeedback
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT00226044	PHASE3	COMPLETED	Rectal and Oral Omeprazole Treatment of Reflux Disease in Infants.
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT03127345	PHASE2	WITHDRAWN	Omega 3 Fatty Acid Treatment for Pediatric Musculoskeletal Health
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age