TENM1

Summary

TENM1 (teneurin transmembrane protein 1, HGNC:8117) is a protein-coding gene on chromosome Xq25, encoding Teneurin-1 (Q9UKZ4). Involved in neural development, regulating the establishment of proper connectivity within the nervous system.

The protein encoded by this gene belongs to the tenascin family and teneurin subfamily. It is expressed in the neurons and may function as a cellular signal transducer. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 10178 — RefSeq curated summary.

At a glance

• Gene–disease (curated): isolated congenital anosmia (Supportive, GenCC) — +2 more curated relationships
• GWAS associations: 7
• Clinical variants (ClinVar): 723 total — 1 likely-pathogenic
• Phenotypes (HPO): 1
• MANE Select transcript: NM_001163278

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8117
Approved symbol	TENM1
Name	teneurin transmembrane protein 1
Location	Xq25
Locus type	gene with protein product
Status	Approved
Aliases	TEN-M1, TEN1
Ensembl gene	ENSG00000009694
Ensembl biotype	protein_coding
OMIM	300588
Entrez	10178

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000371130, ENST00000422452, ENST00000461429

RefSeq mRNA: 3 — MANE Select: NM_001163278 NM_001163278, NM_001163279, NM_014253

CCDS: CCDS14609

Canonical transcript exons

ENST00000422452 — 35 exons

Exon	Start	End
ENSE00000857625	124963537	124963817
ENSE00001024688	124895981	124896241
ENSE00001168728	124382670	124382812
ENSE00001168733	124383634	124384854
ENSE00001168738	124385677	124386064
ENSE00001168750	124392052	124392348
ENSE00001168757	124405031	124405266
ENSE00001168764	124406317	124406489
ENSE00001168768	124420311	124420821
ENSE00001168772	124422272	124422638
ENSE00001168776	124453337	124453491
ENSE00001168787	124497016	124497265
ENSE00001168791	124503560	124503703
ENSE00001168796	124520517	124520784
ENSE00001168803	124523364	124523625
ENSE00001168814	124529864	124529983
ENSE00001168824	124546874	124547090
ENSE00001168831	124561671	124561817
ENSE00001168839	124563749	124563772
ENSE00001168847	124565375	124565560
ENSE00001168855	124641791	124641991
ENSE00001168863	124645143	124645337
ENSE00001168872	124646709	124646810
ENSE00001168878	124651914	124652124
ENSE00001168885	124653584	124653783
ENSE00001168891	124671683	124671835
ENSE00001168899	124705013	124705251
ENSE00001168907	124736957	124737197
ENSE00001435132	124894296	124894352
ENSE00001454404	124375903	124381294
ENSE00003547080	124487209	124487229
ENSE00003694190	124481732	124481964
ENSE00003973285	125203804	125204312
ENSE00003973286	125184708	125184782
ENSE00003973287	125185643	125185709

Expression profiles

Bgee: expression breadth ubiquitous, 218 present calls, max score 95.63.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1413 / max 53.1294, expressed in 41 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
200394	0.0749	33
200411	0.0323	4
200410	0.0175	3
200409	0.0166	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar vermis	UBERON:0004720	95.63	gold quality
paraflocculus	UBERON:0005351	93.69	gold quality
endothelial cell	CL:0000115	90.56	gold quality
cerebellum	UBERON:0002037	85.35	gold quality
Brodmann (1909) area 23	UBERON:0013554	85.29	gold quality
tendon of biceps brachii	UBERON:0008188	84.93	gold quality
cerebellar cortex	UBERON:0002129	84.38	gold quality
cerebellar hemisphere	UBERON:0002245	84.20	gold quality
right hemisphere of cerebellum	UBERON:0014890	83.94	gold quality
tendon	UBERON:0000043	81.68	gold quality
calcaneal tendon	UBERON:0003701	80.06	gold quality
right uterine tube	UBERON:0001302	78.49	gold quality
liver	UBERON:0002107	78.40	gold quality
right lobe of liver	UBERON:0001114	78.03	gold quality
entorhinal cortex	UBERON:0002728	77.90	gold quality
middle temporal gyrus	UBERON:0002771	76.90	gold quality
CA1 field of hippocampus	UBERON:0003881	76.73	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.55	gold quality
Brodmann (1909) area 10	UBERON:0013541	76.15	gold quality
primary visual cortex	UBERON:0002436	73.65	gold quality
lower esophagus muscularis layer	UBERON:0035833	73.24	gold quality
lower esophagus	UBERON:0013473	73.14	gold quality
thymus	UBERON:0002370	72.94	gold quality
mucosa of stomach	UBERON:0001199	72.31	gold quality
cortical plate	UBERON:0005343	72.25	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	72.09	gold quality
superior frontal gyrus	UBERON:0002661	72.07	gold quality
orbitofrontal cortex	UBERON:0004167	71.12	silver quality
pituitary gland	UBERON:0000007	71.02	gold quality
skin of hip	UBERON:0001554	71.02	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	71.05
E-HCAD-25	yes	38.55
E-ANND-3	yes	7.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

327 targeting TENM1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-12136	99.98	72.81	5713

Literature-anchored findings (GeneRIF, showing 16)

• teneurin-1 plays a role in intracellular signaling (PMID:15777793)
• Data show that human teneurin-1 is directly regulated by EMX2 at a conserved promoter region upstream of the transcription start site, and identify and characterize the EMX2 dependent promoter element of human teneurin-1. (PMID:21651764)
• Subsequent analysis showed that the deletion in both cousins was identical and involved the whole SH2D1A gene and a part of the adjacent ODZ1 gene. (PMID:22271700)
• Studies indicate that teneurin-1 has been suggested as a candidate target gene for X-lined mental retardation. (PMID:25152333)
• The teneurin-1 intracellular domain binds HINT1, thus switching on MITF-dependent transcription of GPNMB. (PMID:25648896)
• This study identified predicted pathogenic, hemizygous variants on chromosome X in disease genes TENM1. (PMID:25666757)
• Data suggest teneurin-1/TENM1 (and possibly TENM3) undergoes proteolysis to TCAPs (teneurin C-terminal associated peptides) that form intercellular adhesive units with latrophilin; signaling via TENM1 TCAPs appears to regulate reproduction. [REVIEW] (PMID:26485751)
• Results of our study, that describes a new Tenm1 mouse, agree with the hypothesis that TENM1 has a role in olfaction. However, additional studies should be done in larger Congenital general anosmia (CGA) cohorts, to provide statistical evidence that loss-of-function mutations in TENM1 can solely cause the disease in our and other CGA cases (PMID:27040985)
• ODZ1, a protein that participates in the embryonic development of the brain, is also involved in cancer progression by promoting the growth and invasion capabilities of GSCs via a transcriptional pathway that induces the expression of RhoA and activation of downstream ROCK. (PMID:27641332)
• Taken together, the results indicate that distinct pathways are involved in papillary thyroid cancer progression, and TENM1 is a potential marker of cancer progression. (PMID:28004221)
• MicroRNA-486 inhibits cell proliferation, invasion and migration via down-regulating the TENM1 expressions and affecting ERK and Akt signaling pathways and epithelial-to-mesenchymal transition in papillary thyroid carcinoma. (PMID:31646573)
• Glioblastoma invasion factor ODZ1 is induced by microenvironmental signals through activation of a Stat3-dependent transcriptional pathway. (PMID:34376733)
• Identification and functional modelling of plausibly causative cis-regulatory variants in a highly-selected cohort with X-linked intellectual disability. (PMID:34388204)
• HIF2alpha Upregulates the Migration Factor ODZ1 under Hypoxia in Glioblastoma Stem Cells. (PMID:35054927)
• A Potential Four-Gene Signature and Nomogram for Predicting the Overall Survival of Papillary Thyroid Cancer. (PMID:36193505)
• The Invasion Factor ODZ1 Is Upregulated through an Epidermal Growth Factor Receptor-Induced Pathway in Primary Glioblastoma Cells. (PMID:38727302)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	tenm1	ENSDARG00000003403
mus_musculus	Tenm1	ENSMUSG00000016150
rattus_norvegicus	Tenm1	ENSRNOG00000062454
drosophila_melanogaster	Ten-m	FBGN0004449
drosophila_melanogaster	Ten-a	FBGN0267001
caenorhabditis_elegans		WBGENE00017892
caenorhabditis_elegans		WBGENE00018237

Paralogs (4): NAGPA (ENSG00000103174), TENM2 (ENSG00000145934), TENM4 (ENSG00000149256), TENM3 (ENSG00000218336)

Protein

Protein identifiers

Teneurin-1 — Q9UKZ4 (reviewed: Q9UKZ4)

Alternative names: Protein Odd Oz/ten-m homolog 1, Tenascin-M1, Teneurin transmembrane protein 1

All UniProt accessions (2): Q9UKZ4, A0A8Z5AZJ6

UniProt curated annotations — full annotation on UniProt →

Function. Involved in neural development, regulating the establishment of proper connectivity within the nervous system. May function as a cellular signal transducer. Plays a role in the regulation of neuroplasticity in the limbic system. Mediates a rapid reorganization of actin- and tubulin-based cytoskeleton elements with an increase in dendritic arborization and spine density formation of neurons in the hippocampus and amygdala. Induces BDNF transcription inhibition in neurons. Activates the mitogen-activated protein (MAP) kinase 2 (MEK2) and extracellular signal-regulated kinase (ERK) cascade. Also acts as a bioactive neuroprotective peptide on limbic neurons of the brain and regulates stress-induced behavior: attenuates alkalosis-associated necrotic cell death and the effects of corticotropin-releasing factor (CRF) on c-fos/FOS induction and on the reinstatement of cocaine seeking. Induces gene transcription activation.

Subunit / interactions. Homodimer; disulfide-linked. Heterodimer with either TENM2 or TENM3. May also form heterodimer with TENM4. Ten-1 ICD interacts with SORBS1 (via third SH3 domain). Interacts with MBD1. Ten-1 ICD interacts with HINT1.

Subcellular location. Cell membrane Nucleus. Nucleus speckle. Nucleus matrix. Cytoplasm. Cytoskeleton Nucleus. Cell membrane.

Tissue specificity. Expressed in fetal brain.

Post-translational modifications. Derives from the plasma membrane form by proteolytic processing. Further proteolytic cleavage may be generated.

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.

Miscellaneous. Binds to the plasma membrane and may be internalized by a receptor- and caveolae-mediated endocytosis manner to reach cytosolic compartments in a dynamin-dependent manner.

Similarity. Belongs to the tenascin family. Teneurin subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UKZ4-1	1	yes
Q9UKZ4-2	2

RefSeq proteins (3): NP_001156750, NP_001156751, NP_055068 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000742	EGF	Domain
IPR006530	YD	Repeat
IPR009471	Ten_N	Domain
IPR011042	6-blade_b-propeller_TolB-like	Homologous_superfamily
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 (109 total): repeat 28, disulfide bond 22, glycosylation site 13, sequence variant 10, domain 9, sequence conflict 9, modified residue 4, chain 3, topological domain 2, region of interest 2, short sequence motif 2, compositionally biased region 2, transmembrane region 1, site 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

No AlphaFold model available for Q9UKZ4 — 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): 2595–2596 (cleavage)

Post-translational modifications (4): 105, 109, 116, 2580

Disulfide bonds (22): 532–542, 536–547, 549–558, 567–578, 580–589, 596–607, 601–612, 614–623, 628–639, 633–644, 646–655, 666–679, 681–690, 695–705, 699–710, 712–721, 726–736, 730–741, 743–752, 765–775 …

Glycosylation sites (13): 433, 905, 1084, 1550, 1567, 1663, 1699, 1757, 1781, 1842, 2145, 2285, 2602

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 517 (showing top): GOBP_RNA_TEMPLATED_DNA_BIOSYNTHETIC_PROCESS, GOBP_CHROMOSOME_ORGANIZATION, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, HNF3ALPHA_Q6, GOBP_NEGATIVE_REGULATION_OF_TELOMERE_MAINTENANCE_VIA_TELOMERASE, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_TELOMERE_CAPPING, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_PEPTIDYL_SERINE_MODIFICATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_TRANSCRIPTION_BY_RNA_POLYMERASE_III, GOBP_TELOMERE_MAINTENANCE_VIA_TELOMERE_LENGTHENING

GO Biological Process (12): regulation of transcription by RNA polymerase III (GO:0006359), immune response (GO:0006955), neuropeptide signaling pathway (GO:0007218), nervous system development (GO:0007399), negative regulation of cell population proliferation (GO:0008285), positive regulation of actin filament polymerization (GO:0030838), positive regulation of peptidyl-serine phosphorylation (GO:0033138), positive regulation of MAP kinase activity (GO:0043406), neuron development (GO:0048666), positive regulation of filopodium assembly (GO:0051491), positive regulation of intracellular protein transport (GO:0090316), signal transduction (GO:0007165)

GO Molecular Function (5): heparin binding (GO:0008201), protein homodimerization activity (GO:0042803), protein heterodimerization activity (GO:0046982), cell adhesion molecule binding (GO:0050839), identical protein binding (GO:0042802)

GO Cellular Component (12): extracellular region (GO:0005576), nucleus (GO:0005634), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), nuclear matrix (GO:0016363), nuclear speck (GO:0016607), neuron projection (GO:0043005), perinuclear region of cytoplasm (GO:0048471), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
intracellular membrane-bounded organelle	3
cytoplasm	3
protein dimerization activity	2
protein binding	2
endomembrane system	2
regulation of DNA-templated transcription	1
transcription by RNA polymerase III	1
immune system process	1
response to stimulus	1
G protein-coupled receptor signaling pathway	1
system development	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
actin filament polymerization	1
regulation of actin filament polymerization	1
positive regulation of protein polymerization	1
positive regulation of cytoskeleton organization	1
positive regulation of supramolecular fiber organization	1
positive regulation of protein phosphorylation	1
peptidyl-serine phosphorylation	1
regulation of peptidyl-serine phosphorylation	1
MAP kinase activity	1
regulation of MAP kinase activity	1
positive regulation of MAPK cascade	1
positive regulation of protein serine/threonine kinase activity	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
intracellular protein transport	1
positive regulation of intracellular transport	1
regulation of intracellular protein transport	1
positive regulation of protein transport	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1

Protein interactions and networks

STRING

1661 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TENM1	SORBS1	Q9BX66	913
TENM1	ADGRL3	Q9HAR2	670
TENM1	ADGRL1	O94910	617
TENM1	ADGRL2	O95490	611
TENM1	EGF	P01133	562
TENM1	DAG1	Q14118	499
TENM1	TRIM71	Q2Q1W2	448
TENM1	AFF2	P51816	434
TENM1	ANOS1	P23352	416
TENM1	ASTN2	O75129	401
TENM1	DLGAP2	Q9P1A6	387
TENM1	ADGRG2	Q8IZP9	385
TENM1	PABIR3	Q6P4D5	378
TENM1	FAT2	Q9NYQ8	365
TENM1	HINT1	P49773	349
TENM1	PTPRD	P23468	349

IntAct

6 interactions, top by confidence:

A	B	Type	Score
YES1	TENM1	psi-mi:“MI:0407”(direct interaction)	0.440
TENM1	H2BC21	psi-mi:“MI:0915”(physical association)	0.400
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350

BioGRID (24): TENM1 (Proximity Label-MS), TENM1 (Affinity Capture-MS), CSNK2B (Two-hybrid), POLR2J (Two-hybrid), APBB1 (Two-hybrid), BEX1 (Two-hybrid), NUBP1 (Two-hybrid), HINT1 (Two-hybrid), MACF1 (Two-hybrid), PTPN12 (Two-hybrid), FIBP (Two-hybrid), PICALM (Two-hybrid), GNB2L1 (Two-hybrid), HINT1 (Co-localization), TENM1 (Proximity Label-MS)

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	219
Likely benign	32
Benign	40

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
982217	NM_001163278.2(TENM1):c.4874T>G (p.Leu1625Arg)	Likely pathogenic

SpliceAI

6135 predictions. Top by Δscore:

Variant	Effect	Δscore
X:124386061:CAGA:C	acceptor_gain	1.0000
X:124386065:C:CC	acceptor_gain	1.0000
X:124405029:AC:A	donor_gain	1.0000
X:124405030:CC:C	donor_gain	1.0000
X:124405078:T:TA	donor_gain	1.0000
X:124405262:ATTTT:A	acceptor_gain	1.0000
X:124405263:TTTT:T	acceptor_gain	1.0000
X:124405264:TTT:T	acceptor_gain	1.0000
X:124420309:A:AC	donor_gain	1.0000
X:124420310:C:CC	donor_gain	1.0000
X:124420310:CT:C	donor_gain	1.0000
X:124420818:TCAC:T	acceptor_gain	1.0000
X:124420819:CAC:C	acceptor_gain	1.0000
X:124420819:CACC:C	acceptor_gain	1.0000
X:124420820:ACCT:A	acceptor_loss	1.0000
X:124420821:CCTGT:C	acceptor_loss	1.0000
X:124420822:C:CC	acceptor_gain	1.0000
X:124420823:T:A	acceptor_loss	1.0000
X:124422266:TCATA:T	donor_loss	1.0000
X:124422267:CATAC:C	donor_loss	1.0000
X:124422268:ATACC:A	donor_loss	1.0000
X:124422269:TACCT:T	donor_loss	1.0000
X:124422270:ACC:A	donor_loss	1.0000
X:124422271:C:A	donor_loss	1.0000
X:124422634:CGCAC:C	acceptor_gain	1.0000
X:124422636:CAC:C	acceptor_gain	1.0000
X:124422637:ACCT:A	acceptor_loss	1.0000
X:124422639:C:CG	acceptor_loss	1.0000
X:124422640:T:A	acceptor_loss	1.0000
X:124453331:GCCTA:G	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000016119 (X:124716889 T>C,G), RS1000022342 (X:124714313 A>G), RS1000023237 (X:124390144 G>C), RS1000026866 (X:124589566 A>C,T), RS1000027734 (X:124733521 G>A,C), RS1000031500 (X:124524594 A>G), RS1000032350 (X:124576012 C>T), RS1000041437 (X:124727436 GA>G), RS1000060644 (X:124646677 C>T), RS1000075469 (X:124578800 T>C), RS1000076703 (X:124667894 T>C), RS1000077747 (X:124475149 A>T), RS1000085852 (X:124779773 G>A), RS1000091529 (X:124408563 T>A), RS1000094995 (X:125087538 G>A)

Disease associations

OMIM: gene MIM:300588 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
isolated congenital anosmia	Supportive	Autosomal dominant
cerebral palsy	Limited	X-linked
anosmia	Limited	X-linked

Mondo (4): sensorineural hearing loss disorder (MONDO:0020678), cerebral palsy (MONDO:0006497), anosmia (MONDO:0010528), isolated congenital anosmia (MONDO:0007137)

Orphanet (1): Moyamoya angiopathy (Orphanet:477768)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000407	Sensorineural hearing impairment

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST001538_3	Immune reponse to smallpox (secreted IFN-alpha)	1.000000e-07
GCST001651_41	Response to amphetamines	7.000000e-06
GCST002187_5	Systolic blood pressure in sickle cell anemia	2.000000e-06
GCST002875_137	Diisocyanate-induced asthma	9.000000e-09
GCST003430_2	Incident myocardial infarction	3.000000e-07
GCST007201_327	Schizophrenia	4.000000e-08
GCST007201_471	Schizophrenia	1.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0004873	cytokine measurement
EFO:0006335	systolic blood pressure
EFO:0006995	response to diisocyanate

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D002547	Cerebral Palsy	C10.228.140.140.254
D000857	Olfaction Disorders	C10.597.751.600; C23.888.592.763.550
C535983	Congenital anosmia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	7
Benzo(a)pyrene	decreases methylation, increases expression, decreases expression	3
Nickel	decreases expression	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
senecionine	decreases expression	1
senkirkine	decreases expression	1
heliotrine	decreases expression	1
trichostatin A	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
enzalutamide	decreases expression	1
(+)-JQ1 compound	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic Trioxide	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases methylation, increases abundance	1
Amphotericin B	decreases expression	1
Catechin	affects cotreatment, increases expression	1
Copper	affects cotreatment, decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Endosulfan	increases expression	1
Ethinyl Estradiol	affects expression	1
Methotrexate	decreases expression	1
N-Nitrosopyrrolidine	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00154830	PHASE4	COMPLETED	Alterations of Functional Activities and Leg Stiffness After Hamstring Lengthening in Cerebral Palsy Children
NCT00432055	PHASE4	COMPLETED	Effects of Botulinum Toxin Type A in Adults With Cerebral Palsy
NCT00549471	PHASE4	TERMINATED	Improvement After Botulinum Toxin Injections to the Arms in Children With Cerebral Palsy
NCT00752934	PHASE4	TERMINATED	Does Oral Baclofen Improve Care and Comfort in Spastic Children in Nursing Homes?
NCT00964639	PHASE4	COMPLETED	Postoperative Pain in Children With Cerebral Palsy After Pelvic and Femoral Osteotomies
NCT01386255	PHASE4	WITHDRAWN	Placebo Controlled Study of Baclofen for GERD in Children With Cerebral Palsy
NCT02546999	PHASE4	COMPLETED	Does Botulinum Toxin A Make Walking Easier in Children With Cerebral Palsy?
NCT02633241	PHASE4	COMPLETED	A Pilot Study of Dexmedetomidine-Propofol in Children Undergoing Magnetic Resonance Imaging
NCT03117322	PHASE4	COMPLETED	Synbiotic, Prebiotics and Probiotics in Children With Cerebral Palsy and Constipation
NCT03648658	PHASE4	UNKNOWN	Paracetamol Study in Patients With Low Muscle Mass
NCT04074265	PHASE4	COMPLETED	Peri-operative Use of a Pain Injection in Pediatric Patients With Cerebral Palsy
NCT04273737	PHASE4	TERMINATED	Amantadine in Treating Cognitive & Motor Impairments in Adolescents and Adults With Cerebral Palsy
NCT04523935	PHASE4	COMPLETED	Excessive Crying in Children With Cerebral Palsy and Communication Deficits
NCT05887765	PHASE4	COMPLETED	Effect of Systematic Dexamethasone on the Duration of Popliteal Nerve Block for Anesthesia After Pediatric Ankle Surgery
NCT06176430	PHASE4	UNKNOWN	Comparison of Twice Weekly Versus Daily Iron Therapy in Treating Anemia in Children With Cerebral Palsy
NCT06189781	PHASE4	RECRUITING	Pain Injection Versus Epidural Anesthesia for Hip Surgery in Pediatric Patients With Cerebral Palsy
NCT00014989	PHASE3	COMPLETED	Beneficial Effects of Antenatal Magnesium Sulfate (BEAM Trial)
NCT00065949	PHASE3	UNKNOWN	Magnesium Sulfate to Prevent Brain Injury in Premature Infants
NCT00367068	PHASE3	COMPLETED	Dutch National ITB Study in Children With Cerebral Palsy
NCT00491894	PHASE3	COMPLETED	Safety and Efficacy Study of Oral Glycopyrrolate Liquid for the Treatment of Pathologic (Chronic Moderate to Severe) Drooling in Pediatric Patients 3 to 18 Years of Age With Cerebral Palsy or Other Neurologic Conditions
NCT00632528	PHASE3	COMPLETED	MEOPA to Improve Physical Therapy Results After Multilevel Surgery
NCT00822029	PHASE3	TERMINATED	Use of Oral Bisphosphonates in the Treatment of Osteoporosis of Non-walking Children With Cerebral Palsy
NCT00922077	PHASE3	COMPLETED	Individualized Neurodevelopmental Treatment
NCT01249417	PHASE3	COMPLETED	Dysport® Pediatric Lower Limb Spasticity Study
NCT01251380	PHASE3	COMPLETED	Dysport® Pediatric Lower Limb Spasticity Follow-on Study
NCT01437644	PHASE3	COMPLETED	The Post-Operative Pain in Cerebral Palsy (POPPIES) Trial
NCT01492608	PHASE3	COMPLETED	Magnesium Sulphate for Preterm Birth (MASP Study)
NCT01603602	PHASE3	COMPLETED	BOTOX® Treatment in Pediatric Upper Limb Spasticity
NCT01603615	PHASE3	COMPLETED	BOTOX® Open-Label Treatment in Pediatric Upper Limb Spasticity
NCT01603628	PHASE3	COMPLETED	BOTOX® Treatment in Pediatric Lower Limb Spasticity
NCT01603641	PHASE3	COMPLETED	BOTOX® Open-Label Treatment in Pediatric Lower Limb Spasticity
NCT01633736	PHASE3	UNKNOWN	Targeted Hip Strength Training in Children With Cerebral Palsy (CP)
NCT01898520	PHASE3	COMPLETED	A Safety, Efficacy and Tolerability Study of Sativex for the Treatment of Spasticity in Children Aged 8 to 18 Years
NCT01929434	PHASE3	COMPLETED	Efficacy of Stem Cell Transplantation Compared to Rehabilitation Treatment of Patients With Cerebral Paralysis
NCT02002884	PHASE3	COMPLETED	Dose-response Study of Efficacy and Safety of Botulinum Toxin Type A to Treat Spasticity of the Arm(s) or of Arm(s) and Leg(s) in Cerebral Palsy
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02839785	PHASE3	TERMINATED	Analgesia and Physiotherapy in Children With Cerebral Palsy (ANTALKINECP)
NCT03110341	PHASE3	UNKNOWN	Effect of Erythropoietin in Premature Infants on White Matter Lesions and Neurodevelopmental Outcome
NCT03302871	PHASE3	COMPLETED	Integrated Management Enhances Functional Gains in Children With Cerebral Palsy Treated by BoNT-A
NCT03306212	PHASE3	COMPLETED	Efficacy of Intermittent Serial Casting on Spastic Wrist Flexion Deformity