TNR

Summary

TNR (tenascin R, HGNC:11953) is a protein-coding gene on chromosome 1q25.1, encoding Tenascin-R (Q92752). Neural extracellular matrix (ECM) protein involved in interactions with different cells and matrix components.

This gene encodes a member of the tenascin family of extracellular matrix glycoproteins. The encoded protein is restricted to the central nervous system. The protein may play a role in neurite outgrowth, neural cell adhesion and modulation of sodium channel function. It is a constituent of perineuronal nets.

Source: NCBI Gene 7143 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder, nonprogressive, with spasticity and transient opisthotonus (Definitive, ClinGen)
• GWAS associations: 10
• Clinical variants (ClinVar): 295 total — 9 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 26
• MANE Select transcript: NM_003285

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11953
Approved symbol	TNR
Name	tenascin R
Location	1q25.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000116147
Ensembl biotype	protein_coding
OMIM	601995
Entrez	7143

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 2 nonsense_mediated_decay

ENST00000367674, ENST00000422274, ENST00000713954, ENST00000713955, ENST00000713977, ENST00000713978

RefSeq mRNA: 2 — MANE Select: NM_003285 NM_001328635, NM_003285

CCDS: CCDS1318

Canonical transcript exons

ENST00000367674 — 23 exons

Exon	Start	End
ENSE00000789989	175396544	175396807
ENSE00001162104	175403140	175403616
ENSE00001445344	175528269	175528369
ENSE00001445345	175743226	175743595
ENSE00001608891	175355503	175355633
ENSE00001617257	175362663	175362809
ENSE00001617834	175379552	175379737
ENSE00001618382	175363708	175363827
ENSE00001647591	175335711	175335807
ENSE00001650570	175391288	175391438
ENSE00001662994	175365010	175365279
ENSE00001670014	175337528	175337679
ENSE00001677785	175324356	175324519
ENSE00001679263	175359612	175359731
ENSE00001707744	175354391	175354523
ENSE00001708080	175367208	175367297
ENSE00001763163	175386032	175386301
ENSE00001781385	175356319	175356462
ENSE00001799901	175330074	175330235
ENSE00001805365	175365875	175366138
ENSE00003706855	175315194	175323476
ENSE00003709708	175393780	175393895
ENSE00004021874	175406216	175406777

Expression profiles

Bgee: expression breadth ubiquitous, 109 present calls, max score 98.27.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 3.3060 / max 272.7187, expressed in 123 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
16003	3.0637	123
16002	0.1122	70
16004	0.0810	55
16005	0.0490	38

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
CA1 field of hippocampus	UBERON:0003881	98.27	gold quality
entorhinal cortex	UBERON:0002728	98.25	gold quality
inferior vagus X ganglion	UBERON:0005363	98.18	gold quality
medulla oblongata	UBERON:0001896	97.51	gold quality
subthalamic nucleus	UBERON:0001906	97.51	gold quality
superior vestibular nucleus	UBERON:0007227	97.39	gold quality
ventral tegmental area	UBERON:0002691	97.31	gold quality
postcentral gyrus	UBERON:0002581	97.30	gold quality
inferior olivary complex	UBERON:0002127	97.23	gold quality
parietal lobe	UBERON:0001872	97.14	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.77	gold quality
Brodmann (1909) area 46	UBERON:0006483	96.77	gold quality
dorsal plus ventral thalamus	UBERON:0001897	96.73	gold quality
orbitofrontal cortex	UBERON:0004167	96.71	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	96.70	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.18	gold quality
substantia nigra pars compacta	UBERON:0001965	96.14	gold quality
middle temporal gyrus	UBERON:0002771	96.07	gold quality
pons	UBERON:0000988	95.76	gold quality
superior frontal gyrus	UBERON:0002661	95.75	gold quality
lateral globus pallidus	UBERON:0002476	95.38	gold quality
lateral nuclear group of thalamus	UBERON:0002736	95.30	gold quality
middle frontal gyrus	UBERON:0002702	95.20	gold quality
temporal lobe	UBERON:0001871	94.89	gold quality
frontal pole	UBERON:0002795	94.87	gold quality
Brodmann (1909) area 10	UBERON:0013541	94.29	gold quality
paraflocculus	UBERON:0005351	94.15	gold quality
corpus callosum	UBERON:0002336	93.80	gold quality
cranial nerve II	UBERON:0000941	93.15	gold quality
amygdala	UBERON:0001876	92.83	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-GEOD-180759	yes	4894.61
E-HCAD-30	yes	3975.36
E-HCAD-35	yes	3963.99
E-GEOD-84465	yes	3717.54
E-HCAD-25	yes	2693.57
E-MTAB-11121	yes	769.68
E-MTAB-9435	yes	718.05
E-GEOD-137537	yes	6.74
E-ANND-3	yes	6.44
E-GEOD-93593	yes	4.07
E-GEOD-99795	no	1.82

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

63 targeting TNR, 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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-12130	99.75	65.47	452
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-516A-3P	99.46	67.96	1378
HSA-MIR-516B-3P	99.46	67.96	1378
HSA-MIR-7162-5P	99.46	68.08	1368
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119

Literature-anchored findings (GeneRIF, showing 10)

• citation presents comparison with human gene. (PMID:12927810)
• Tenascin R is expressed and glycosylated in neurons (PMID:14681222)
• An extracellular matrix molecule TNR and its associated carbohydrate human natural killer cell glycan (HNK-1) provide conditions beneficial for induction of long-term potentiation in the hippocampus. (PMID:17537973)
• The researchers found evidence that the tenascin R gene is a potential susceptiblity or marker gene for IgA nephropathy. (PMID:19890582)
• KIAA0510, the 3’-untranslated region of the tenascin-R gene, and tenascin-R are overexpressed in pilocytic astrocytomas (PMID:20202125)
• results show that tenascin-R expression is tightly regulated in a spatiotemporal manner during brain development, especially cortical plate formation; its pattern of expression suggests a role for tenascin-R in corticogenesis (PMID:21456020)
• TnC and TnR play important roles in nervous and immune systems. [Review] (PMID:23269478)
• TNR is a novel candidate for Biopolar Disorder in humans and anxiety in mice (PMID:26190982)
• Two genes, TNR (and TNK2), were found to have genetic variations linked to familial Parkinson’s Disease. (PMID:26595808)
• Study observed a genome-wide significant association between attention deficit hyperactivity disorder and rs6686722, mapped to the Tenascin R (TNR) gene. (PMID:30563984)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tnr	ENSDARG00000020771
mus_musculus	Tnr	ENSMUSG00000015829
rattus_norvegicus	Tnr	ENSRNOG00000002468

Paralogs (25): TNC (ENSG00000041982), FCN1 (ENSG00000085265), ANGPT2 (ENSG00000091879), ANGPT4 (ENSG00000101280), FGL1 (ENSG00000104760), FN1 (ENSG00000115414), ANGPTL1 (ENSG00000116194), TNN (ENSG00000120332), FGL2 (ENSG00000127951), FIBCD1 (ENSG00000130720), ANGPTL6 (ENSG00000130812), ANGPTL3 (ENSG00000132855), ANGPTL2 (ENSG00000136859), FCN3 (ENSG00000142748), FNDC7 (ENSG00000143107), ANGPT1 (ENSG00000154188), FCN2 (ENSG00000160339), MFAP4 (ENSG00000166482), ANGPTL4 (ENSG00000167772), TNXB (ENSG00000168477), FGG (ENSG00000171557), FGA (ENSG00000171560), FGB (ENSG00000171564), ANGPTL7 (ENSG00000171819), ANGPTL5 (ENSG00000187151)

Protein

Protein identifiers

Tenascin-R — Q92752 (reviewed: Q92752)

Alternative names: Janusin, Restrictin

All UniProt accessions (6): Q92752, A0AAQ5BH57, A0AAQ5BH84, A0AAQ5BH92, A0AAQ5BHB2, H0Y668

UniProt curated annotations — full annotation on UniProt →

Function. Neural extracellular matrix (ECM) protein involved in interactions with different cells and matrix components. These interactions can influence cellular behavior by either evoking a stable adhesion and differentiation, or repulsion and inhibition of neurite growth. Binding to cell surface gangliosides inhibits RGD-dependent integrin-mediated cell adhesion and results in an inhibition of PTK2/FAK1 (FAK) phosphorylation and cell detachment. Binding to membrane surface sulfatides results in a oligodendrocyte adhesion and differentiation. Interaction with CNTN1 induces a repulsion of neurons and an inhibition of neurite outgrowth. Interacts with SCN2B may play a crucial role in clustering and regulation of activity of sodium channels at nodes of Ranvier. TNR-linked chondroitin sulfate glycosaminoglycans are involved in the interaction with FN1 and mediate inhibition of cell adhesion and neurite outgrowth. The highly regulated addition of sulfated carbohydrate structure may modulate the adhesive properties of TNR over the course of development and during synapse maintenance.

Subunit / interactions. Forms oligomers. Interacts with CNTN1, TNC, and FN1. Interacts with BCAN and ACAN in a calcium-dependent manner. Interacts with SCN2B, PTPRZ1, and CSPG3.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Brain specific.

Post-translational modifications. Contains N-linked oligosaccharides, O-linked sialylated structures and O-linked chondroitin sulfate glycosaminoglycans. Contains N-linked oligosaccharides with a sulfated carbohydrate structure. O-glycosylated on Thr-36 or Thr-37 with a core 1 or possibly core 8 glycan.

Disease relevance. Neurodevelopmental disorder, non-progressive, with spasticity and transient opisthotonus (NEDSTO) [MIM:619653] An autosomal recessive disorder characterized by delayed motor milestones, delayed walking, speech delay, axial hypotonia, and peripheral spasticity apparent from infancy or early childhood. Affected individuals often show transient opisthotonic posturing in infancy, and later show abnormal involuntary movements. Variably impaired intellectual development, and brain myelination defects are present in some patients. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The EGF-like domains mediate interaction with CNTN1. The fibronectin type-III domains 3-5 mediate interaction with BCAN. The fibronectin type-III domains 1-2 and 7-9 mediate interaction with SCN2B.

Similarity. Belongs to the tenascin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q92752-1	1	yes
Q92752-2	2

RefSeq proteins (2): NP_001315564, NP_003276* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000742	EGF	Domain
IPR002181	Fibrinogen_a/b/g_C_dom	Domain
IPR003961	FN3_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR014716	Fibrinogen_a/b/g_C_1	Homologous_superfamily
IPR036056	Fibrinogen-like_C	Homologous_superfamily
IPR036116	FN3_sf	Homologous_superfamily
IPR050991	ECM_Regulatory_Proteins	Family

Pfam: PF00041, PF00147, PF23106, PF25024

UniProt features (75 total): glycosylation site 17, domain 15, sequence variant 11, strand 11, helix 10, disulfide bond 3, turn 2, signal peptide 1, chain 1, coiled-coil region 1, modified residue 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
8FNA	X-RAY DIFFRACTION	1.75
8FN9	X-RAY DIFFRACTION	1.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92752-F1	79.00	0.26

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 (1): 724

Disulfide bonds (3): 292–301, 297–312, 314–323

Glycosylation sites (17): 36, 37, 55, 176, 180, 198, 271, 278, 302, 392, 470, 581, 791, 874, 1036, 1046, 1261

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-3000178	ECM proteoglycans
R-HSA-1474244	Extracellular matrix organization

MSigDB gene sets: 0 (showing top):

GO Biological Process (26): cell adhesion (GO:0007155), neuron cell-cell adhesion (GO:0007158), nervous system development (GO:0007399), axon guidance (GO:0007411), associative learning (GO:0008306), negative regulation of neuron projection development (GO:0010977), telencephalon cell migration (GO:0022029), negative regulation of cell-cell adhesion (GO:0022408), regulation of cell adhesion (GO:0030155), extracellular matrix organization (GO:0030198), regulation of cell migration (GO:0030334), synaptic transmission, glutamatergic (GO:0035249), locomotory exploration behavior (GO:0035641), regulation of cell differentiation (GO:0045595), axon extension involved in regeneration (GO:0048677), negative regulation of axon extension involved in regeneration (GO:0048692), negative regulation of synaptic transmission (GO:0050805), synapse organization (GO:0050808), neuromuscular process controlling balance (GO:0050885), positive regulation of synaptic transmission, glutamatergic (GO:0051968), positive regulation of transmission of nerve impulse (GO:0051971), long-term synaptic potentiation (GO:0060291), neuroblast migration (GO:0097402), negative regulation of axon extension (GO:0030517), axon extension (GO:0048675), modulation of chemical synaptic transmission (GO:0050804)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (9): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cell surface (GO:0009986), extracellular matrix (GO:0031012), membrane raft (GO:0045121), perineuronal net (GO:0072534), tenascin complex (GO:0090733), Schaffer collateral - CA1 synapse (GO:0098685), glutamatergic synapse (GO:0098978)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Extracellular matrix organization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell-cell adhesion	2
regulation of cellular process	2
chemical synaptic transmission	2
cellular anatomical structure	2
synapse	2
cellular process	1
system development	1
axonogenesis	1
neuron projection guidance	1
learning	1
regulation of neuron projection development	1
neuron projection development	1
negative regulation of cell projection organization	1
telencephalon development	1
forebrain cell migration	1
negative regulation of cell adhesion	1
regulation of cell-cell adhesion	1
cell adhesion	1
extracellular structure organization	1
external encapsulating structure organization	1
cell migration	1
regulation of cell motility	1
locomotory behavior	1
exploration behavior	1
cell differentiation	1
regulation of developmental process	1
regeneration	1
axon extension	1
sprouting of injured axon	1
negative regulation of axon extension	1
axon extension involved in regeneration	1
negative regulation of sprouting of injured axon	1
negative regulation of cell communication	1
negative regulation of signaling	1
modulation of chemical synaptic transmission	1
cell junction organization	1
musculoskeletal movement	1
neuromuscular process	1
synaptic transmission, glutamatergic	1
positive regulation of synaptic transmission	1

Protein interactions and networks

STRING

1384 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TNR	CYP21A2	P04033	497
TNR	CNTN1	Q12860	370
TNR	EGF	P01133	299
TNR	BSN	Q9UPA5	280
TNR	RIMS2	Q9UQ26	275
TNR	NPEPPS	P55786	252
TNR	NFASC	O94856	248
TNR	TMEM235	A6NFC5	239
TNR	WHR1	P49842	231
TNR	ATF6B	Q99941	223
TNR	VWC2L	B2RUY7	220
TNR	SPTLC1	O15269	209
TNR	RPH3A	Q9Y2J0	208
TNR	CSPG5	O95196	206
TNR	PVALB	P20472	205

IntAct

6 interactions, top by confidence:

A	B	Type	Score
TNR	TLR4	psi-mi:“MI:0407”(direct interaction)	0.440
PRNP	CARNS1	psi-mi:“MI:0914”(association)	0.350
PRNP	WDR91	psi-mi:“MI:0914”(association)	0.350
MYC		psi-mi:“MI:0914”(association)	0.350
TRIM54	TNR	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (15): TNR (Two-hybrid), TNR (Two-hybrid), NCK2 (Two-hybrid), POLR3C (Two-hybrid), WDYHV1 (Two-hybrid), LGALS14 (Two-hybrid), CCDC146 (Two-hybrid), TNR (Affinity Capture-MS), ACAN (Reconstituted Complex), TNR (Two-hybrid), TNR (Affinity Capture-MS), PTPRZ1 (Reconstituted Complex), NCAN (Reconstituted Complex), TNR (Affinity Capture-MS), TNR (Co-fractionation)

ESM2 similar proteins: A2AED3, B1AUH1, B2RU80, B3DK56, B3EX02, F1NWE3, O14522, O42422, O73875, O88488, P08922, P08941, P0C5E4, P16621, P23467, P28827, P28828, P35822, P35992, P53767, P54755, P54757, P54759, Q00546, Q02763, Q02858, Q05546, Q06806, Q06807, Q15262, Q15375, Q2EY13, Q2EY15, Q2VWP7, Q2VWP9, Q5R412, Q5VTL7, Q61772, Q63132, Q64455

Diamond homologs: A0A8J8, A2AV25, D8VNS7, D8VNS8, D8VNS9, D8VNT0, E2IYB3, E9PV24, O00602, O08538, O15123, O18920, O35460, O35462, O35608, O43827, O70165, O70497, O75636, O77802, O93526, O95841, P02671, P02675, P02676, P02678, P02679, P02680, P04115, P06399, P10039, P12799, P12804, P14448, P14480, P17634, P19477, P21520, P22105, P24821

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	4
Uncertain significance	215
Likely benign	36
Benign	14

Top pathogenic / likely-pathogenic (13)

Variant ID	HGVS	Classification
1328505	NM_003285.3(TNR):c.1475del (p.Arg492fs)	Pathogenic
1686264	NM_003285.3(TNR):c.3916A>C (p.Thr1306Pro)	Pathogenic
1686265	NM_003285.3(TNR):c.2818del (p.Glu940fs)	Pathogenic
4689372	NM_003285.3(TNR):c.861C>A (p.Tyr287Ter)	Pathogenic
691951	NM_003285.3(TNR):c.2713C>T (p.Arg905Ter)	Pathogenic
691952	NM_003285.3(TNR):c.2744_2745del (p.Val915fs)	Pathogenic
691953	NM_003285.3(TNR):c.3574C>T (p.Arg1192Trp)	Pathogenic
691954	NM_003285.3(TNR):c.1899del (p.Glu634fs)	Pathogenic
691955	NM_003285.3(TNR):c.207C>G (p.Tyr69Ter)	Pathogenic
2146033	NM_003285.3(TNR):c.1240+1G>A	Likely pathogenic
3341364	NM_003285.3(TNR):c.1305G>A (p.Trp435Ter)	Likely pathogenic
691957	NM_003285.3(TNR):c.1594G>A (p.Asp532Asn)	Likely pathogenic
691958	NM_003285.3(TNR):c.1189G>A (p.Ala397Thr)	Likely pathogenic

SpliceAI

5670 predictions. Top by Δscore:

Variant	Effect	Δscore
1:175323384:C:CA	donor_gain	1.0000
1:175324350:GCTTA:G	donor_loss	1.0000
1:175324351:CTTA:C	donor_loss	1.0000
1:175324352:TTACC:T	donor_loss	1.0000
1:175324353:TA:T	donor_loss	1.0000
1:175324354:A:AC	donor_gain	1.0000
1:175324355:C:CC	donor_gain	1.0000
1:175324355:CCTGA:C	donor_gain	1.0000
1:175324382:T:TA	donor_gain	1.0000
1:175324383:C:A	donor_gain	1.0000
1:175324515:GTCCC:G	acceptor_gain	1.0000
1:175324516:TCCC:T	acceptor_gain	1.0000
1:175324517:CCC:C	acceptor_gain	1.0000
1:175324517:CCCC:C	acceptor_gain	1.0000
1:175324518:CC:C	acceptor_gain	1.0000
1:175324518:CCC:C	acceptor_gain	1.0000
1:175324519:CC:C	acceptor_gain	1.0000
1:175324519:CCTG:C	acceptor_loss	1.0000
1:175324520:C:CC	acceptor_gain	1.0000
1:175324520:CTGCA:C	acceptor_loss	1.0000
1:175330093:T:TA	donor_gain	1.0000
1:175335713:AG:A	donor_gain	1.0000
1:175335714:G:C	donor_gain	1.0000
1:175335724:AT:A	donor_gain	1.0000
1:175337526:A:AC	donor_gain	1.0000
1:175337526:ACAAT:A	donor_gain	1.0000
1:175337527:C:CC	donor_gain	1.0000
1:175337527:CAAT:C	donor_gain	1.0000
1:175337527:CAATC:C	donor_gain	1.0000
1:175354385:CCTCA:C	donor_loss	1.0000

AlphaMissense

8891 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:175324405:C:G	C1303S	1.000
1:175324406:A:T	C1303S	1.000
1:175324444:C:G	C1290S	1.000
1:175324445:A:T	C1290S	1.000
1:175323456:C:A	W1326C	0.999
1:175323456:C:G	W1326C	0.999
1:175323465:C:A	W1323C	0.999
1:175323465:C:G	W1323C	0.999
1:175323476:C:A	G1320C	0.999
1:175324404:G:C	C1303W	0.999
1:175324405:C:A	C1303F	0.999
1:175324405:C:T	C1303Y	0.999
1:175324406:A:G	C1303R	0.999
1:175324416:C:A	W1299C	0.999
1:175324416:C:G	W1299C	0.999
1:175324418:A:G	W1299R	0.999
1:175324418:A:T	W1299R	0.999
1:175324419:C:A	W1298C	0.999
1:175324419:C:G	W1298C	0.999
1:175324421:A:G	W1298R	0.999
1:175324421:A:T	W1298R	0.999
1:175324443:A:C	C1290W	0.999
1:175324444:C:A	C1290F	0.999
1:175324444:C:T	C1290Y	0.999
1:175324445:A:G	C1290R	0.999
1:175330187:C:G	R1227P	0.999
1:175330190:A:G	L1226P	0.999
1:175335717:A:G	W1209R	0.999
1:175335717:A:T	W1209R	0.999
1:175335760:C:A	W1194C	0.999

dbSNP variants (sampled 300 via entrez): RS1000006797 (1:175341186 C>G), RS1000008955 (1:175734219 C>A,T), RS1000014955 (1:175696809 G>A,T), RS1000023536 (1:175427959 C>T), RS1000028745 (1:175505966 G>A,C,T), RS1000038620 (1:175505803 G>A), RS1000040140 (1:175734504 G>T), RS1000049438 (1:175615070 G>A), RS1000050252 (1:175664429 G>A), RS1000060822 (1:175544304 C>A), RS1000069052 (1:175576786 A>G), RS1000071739 (1:175342710 G>A,T), RS1000073484 (1:175356985 C>T), RS1000139149 (1:175571365 G>C,T), RS1000140114 (1:175499876 G>A,T)

Disease associations

OMIM: gene MIM:601995 | disease phenotypes: MIM:619653, MIM:168600, MIM:614162

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder, nonprogressive, with spasticity and transient opisthotonus	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
neurodevelopmental disorder, nonprogressive, with spasticity and transient opisthotonus	Definitive	AR

Mondo (3): neurodevelopmental disorder, nonprogressive, with spasticity and transient opisthotonus (MONDO:0859212), Parkinson disease (MONDO:0005180), autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome (MONDO:0013599)

Orphanet (2): STAT1-related autoimmune enteropathy and endocrinopathy-susceptibility to chronic infections syndrome (Orphanet:391487), NON RARE IN EUROPE: Parkinson disease (Orphanet:319705)

HPO phenotypes

26 total (26 of 26 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000514	Slow saccadic eye movements
HP:0000750	Delayed speech and language development
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001266	Choreoathetosis
HP:0001270	Motor delay
HP:0001285	Spastic tetraparesis
HP:0001300	Parkinsonism
HP:0001332	Dystonia
HP:0001338	Partial agenesis of the corpus callosum
HP:0001347	Hyperreflexia
HP:0002179	Opisthotonus
HP:0002186	Apraxia
HP:0002188	Delayed CNS myelination
HP:0002395	Lower limb hyperreflexia
HP:0002540	Inability to walk
HP:0003593	Infantile onset
HP:0007149	Distal upper limb amyotrophy
HP:0007305	CNS demyelination
HP:0007325	Generalized dystonia
HP:0007350	Upper limb hyperreflexia
HP:0008936	Axial hypotonia
HP:0008959	Distal upper limb muscle weakness
HP:0033725	Thin corpus callosum

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST000107_12	Tonometry	4.000000e-06
GCST005358_1	Disease progression to choroidal neovascularization form in age-related macular degeneration	2.000000e-08
GCST005803_12	Corneal astigmatism	7.000000e-06
GCST005951_39	Body mass index	4.000000e-08
GCST006485_1	Telomere length	2.000000e-06
GCST006916_2	Attention deficit hyperactivity disorder	3.000000e-08
GCST007673_5	3-month functional outcome in ischaemic stroke (modified Rankin score)	4.000000e-06
GCST008469_1	Liver fibrosis in non-alcoholic fatty liver disease	5.000000e-06
GCST011153_1	Testosterone levels x fluid intelligence interaction	3.000000e-08
GCST012034_1	Sleep (1/2-day periodicity)	5.000000e-08

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0008336	disease progression measurement
EFO:1002040	Corneal astigmatism
EFO:0004340	body mass index
EFO:0009603	stroke outcome severity measurement
EFO:0004337	intelligence
EFO:0004908	testosterone measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D010300	Parkinson Disease	C10.228.140.079.862.500; C10.228.662.600.400; C10.574.928.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
peracetylated N-azidoacetylmannosamine	decreases expression	1
propionaldehyde	decreases expression	1
bisphenol A	affects cotreatment, affects methylation	1
O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate	affects expression, affects response to substance	1
mono-(2-ethylhexyl)phthalate	decreases methylation, increases abundance	1
perfluorooctanoic acid	affects methylation	1
benzo(e)pyrene	increases methylation	1
Fulvestrant	affects cotreatment, affects methylation	1
Vehicle Emissions	increases methylation	1
Benzo(a)pyrene	affects methylation	1
Diethylhexyl Phthalate	increases abundance, decreases methylation	1
Ivermectin	decreases expression	1
Lead	decreases expression	1
Methapyrilene	increases methylation	1
Phthalic Acids	decreases methylation	1
Tamoxifen	increases expression	1
Aflatoxin B1	decreases methylation	1
Asbestos, Serpentine	increases methylation	1
Cadmium Chloride	increases expression	1
Copper Sulfate	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00030979	PHASE4	COMPLETED	Donepezil to Treat Dementia in Parkinson’s Disease
NCT00043849	PHASE4	COMPLETED	Treatment of Agitation/Psychosis in Dementia/Parkinsonism (TAP/DAP)
NCT00095810	PHASE4	COMPLETED	Aripiprazole in Patients With Psychosis Associated With Parkinson’s Disease
NCT00125567	PHASE4	COMPLETED	Stalevo in Early Wearing-Off Patients
NCT00143026	PHASE4	COMPLETED	Study to Compare the Effect of Treatment With Carbidopa/Levodopa/Entacapone on the Quality of Life of Patients With Parkinson’s Disease. This Study is Not Recruiting in the United States
NCT00144300	PHASE4	COMPLETED	Ophthalmologic Safety Study of Pramipexole Immediate Release (IR) Versus Ropinirole in Early Parkinson’s Disease (PD) Patients
NCT00153972	PHASE4	COMPLETED	Dopamine Turnover Rate as Surrogate Parameter for Diagnosis of Early Parkinson’s Disease
NCT00174239	PHASE4	TERMINATED	Study Of Cabaser and Sinemet CR For The Treatment Of Nighttime Symptoms Associated With Parkinson’s Disease.
NCT00215904	PHASE4	COMPLETED	D-serine Adjuvant Treatment for Parkinson’s Disease
NCT00247247	PHASE4	COMPLETED	Comtess® Versus Cabaseril® as Add-on to Levodopa in the Treatment of Parkinsonian Patients Suffering From Wearing- Off.
NCT00272688	PHASE4	COMPLETED	Continuous Delivery of Levodopa in Patients With Advanced Idiopathic Parkinsons Disease - Cost-benefit
NCT00297778	PHASE4	COMPLETED	Pramipexole Versus Placebo in Parkinson’s Disease (PD) Patients With Depressive Symptoms
NCT00304161	PHASE4	COMPLETED	Effectiveness of Antidepressant Treatment for Depression in People With Parkinson’s Disease
NCT00307450	PHASE4	COMPLETED	Efficacy and Safety of Levetiracetam Versus Placebo on Levodopa-induced Dyskinesias in Advanced Parkinson’s Disease
NCT00321854	PHASE4	COMPLETED	Study of (Mirapex) Pramipexole for the Early Treatment of Parkinsons Disease (PD)
NCT00354133	PHASE4	UNKNOWN	Controlled Trial With Deep Brain Stimulation in Patients With Early Parkinson’s Disease
NCT00373087	PHASE4	COMPLETED	COMT Polymorphism and Entacapone Efficacy
NCT00391898	PHASE4	COMPLETED	Efficacy of Levodopa/Carbidopa/Entacapone vs Levodopa/Carbidopa in Parkinson’s Disease Patients With Early Wearing-off
NCT00399477	PHASE4	COMPLETED	A Non-Blinded Study Demonstrating the Effectiveness and Safety of Azilect Alone or in Combination Therapy in Parkinson’s Disease
NCT00402233	PHASE4	COMPLETED	A Randomized, Double-blind, Active (Pramipexole 0.5 mg Tid) and Placebo Controlled, Study of Pramipexole Given 0.5 mg and 0.75 mg Bid Over 12-week Treatment in Early Parkinson’s Disease (PD) Patients
NCT00437125	PHASE4	COMPLETED	Study on the Tolerability of Duloxetine in Depressed Patients With Parkinson’s Disease
NCT00443872	PHASE4	COMPLETED	Efficacy of Orally Disintegrating Selegiline in Parkinson’s Patients Experiencing Adverse Effects With Dopamine Agonists
NCT00455143	PHASE4	TERMINATED	Cognitive Protection - Dexmedetomidine and Cognitive Reserve
NCT00462007	PHASE4	COMPLETED	Study to Evaluate Initiation of Stalevo in Early Wearing-off
NCT00462254	PHASE4	TERMINATED	Ramelteon (ROZEREM) in the Treatment of Sleep Disturbances Associated With Parkinson’s Disease
NCT00477802	PHASE4	TERMINATED	Botulinum Toxin Type A (Botox) in the Management of Levodopa-Induced Peak-Dose Dyskinesias in Parkinson’s Disease
NCT00485069	PHASE4	COMPLETED	REQUIP (Ropinirole Hydrochloride) IR Long-Term Phase 4 Study
NCT00489255	PHASE4	COMPLETED	Safety/Efficacy of Tigan® to Control Nausea/Vomiting Experienced During Apokyn® Initiation and Treatment
NCT00526630	PHASE4	COMPLETED	Methylphenidate for the Treatment of Gait Impairment in Parkinson’s Disease
NCT00561678	PHASE4	COMPLETED	Perioperative Cognitive Function - Dexmedetomidine and Cognitive Reserve
NCT00571285	PHASE4	TERMINATED	Clinical Effects of Vitamin D Repletion in Patients With Parkinson’s Disease
NCT00584025	PHASE4	WITHDRAWN	Keppra IV for the Treatment of Motor Fluctuations in Parkinson’s Disease
NCT00584090	PHASE4	WITHDRAWN	Solifenacin Succinate (VESIcare) for the Treatment of Urinary Incontinence in Parkinson’s Disease
NCT00590122	PHASE4	COMPLETED	Parcopa Versus Carbidopa-levodopa in a Single Dose Cross-over Comparison Study
NCT00594464	PHASE4	COMPLETED	A Trial of Neupro® (Rotigotine Transdermal Patch) in Patients With Parkinson’s Disease Undergoing Surgery
NCT00601978	PHASE4	WITHDRAWN	Carbidopa/Levodopa Versus Carbidopa/Levodopa/Entacapone on Markers of Event Related Potentials (ERPs) in Patients With Idiopathic Parkinson’s Disease (PD) and End-of-dose Wearing Off
NCT00632762	PHASE4	COMPLETED	Long-Term Effects of Amantadine in Parkinsonian (AMANDYSK)
NCT00640159	PHASE4	COMPLETED	Selegiline to Zelapar Switch Study in Parkinson Disease Patients
NCT00642356	PHASE4	TERMINATED	Carbidopa/Levodopa/Entacapone Versus Immediate Release (IR) Carbidopa/Levodopa on Non-motor Symptoms in Patients With Idiopathic Parkinson’s Disease and Demonstrating Non-motor Symptoms of Wearing Off
NCT00646204	PHASE4	COMPLETED	Namenda (Memantine) for Non-motor Symptoms in Parkinson’s Disease