RIC3

Summary

RIC3 (RIC3 acetylcholine receptor chaperone, HGNC:30338) is a protein-coding gene on chromosome 11p15.4, encoding Protein RIC-3 (Q7Z5B4). Molecular chaperone which facilitates proper subunit assembly and surface trafficking of alpha-7 (CHRNA7) and alpha-8 (CHRNA8) nicotinic acetylcholine receptors.

This gene encodes a member of the resistance to inhibitors of cholinesterase 3-like family which functions as a chaperone of specific 5-hydroxytryptamine type 3 receptor and nicotinic acetylcholine receptor subtypes. The encoded protein influences the folding and assembly of these receptor subunits in the endoplasmic reticulum and expression on the cell surface. This protein contains an N-terminal transmembrane domain, a proline-rich spacer, and a cytosolic C-terminal coiled-coil domain. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 79608 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Parkinson disease (Limited, GenCC) — +1 more curated relationship
• GWAS associations: 7
• Clinical variants (ClinVar): 500 total — 6 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 1
• MANE Select transcript: NM_001206671

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30338
Approved symbol	RIC3
Name	RIC3 acetylcholine receptor chaperone
Location	11p15.4
Locus type	gene with protein product
Status	Approved
Aliases	FLJ11608, PRO1385, AYST720
Ensembl gene	ENSG00000166405
Ensembl biotype	protein_coding
OMIM	610509
Entrez	79608

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 6 protein_coding, 4 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000309737, ENST00000335425, ENST00000343202, ENST00000419822, ENST00000425599, ENST00000524799, ENST00000526962, ENST00000528463, ENST00000529035, ENST00000529271, ENST00000530060, ENST00000531450, ENST00000699457

RefSeq mRNA: 9 — MANE Select: NM_001206671 NM_001135109, NM_001206671, NM_001206672, NM_001346690, NM_001346691, NM_001346692, NM_001346693, NM_001346694, NM_024557

CCDS: CCDS44533, CCDS55741, CCDS55742, CCDS7788

Canonical transcript exons

ENST00000309737 — 6 exons

Exon	Start	End
ENSE00002145868	8106056	8111137
ENSE00003499930	8139967	8140193
ENSE00003601864	8138272	8138347
ENSE00003669114	8137378	8137471
ENSE00003681012	8126659	8126807
ENSE00003848333	8168866	8169025

Expression profiles

Bgee: expression breadth ubiquitous, 178 present calls, max score 94.77.

FANTOM5 (CAGE): breadth broad, TPM avg 6.3894 / max 186.5970, expressed in 529 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
118489	6.3894	529

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adenohypophysis	UBERON:0002196	94.77	gold quality
left lobe of thyroid gland	UBERON:0001120	94.68	gold quality
right lobe of thyroid gland	UBERON:0001119	94.56	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.40	gold quality
cerebellar hemisphere	UBERON:0002245	94.13	gold quality
cerebellar cortex	UBERON:0002129	93.93	gold quality
body of pancreas	UBERON:0001150	93.66	gold quality
right uterine tube	UBERON:0001302	92.88	gold quality
thyroid gland	UBERON:0002046	92.09	gold quality
left ovary	UBERON:0002119	92.03	gold quality
pituitary gland	UBERON:0000007	91.56	gold quality
mucosa of stomach	UBERON:0001199	91.36	gold quality
skin of abdomen	UBERON:0001416	91.18	gold quality
minor salivary gland	UBERON:0001830	90.92	gold quality
cerebellum	UBERON:0002037	90.58	gold quality
skin of leg	UBERON:0001511	90.43	gold quality
metanephros cortex	UBERON:0010533	90.19	gold quality
right ovary	UBERON:0002118	90.18	gold quality
lower esophagus muscularis layer	UBERON:0035833	89.82	gold quality
lower esophagus	UBERON:0013473	89.81	gold quality
right frontal lobe	UBERON:0002810	89.72	gold quality
left adrenal gland cortex	UBERON:0035825	89.51	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	89.29	gold quality
left adrenal gland	UBERON:0001234	89.23	gold quality
right adrenal gland cortex	UBERON:0035827	89.14	gold quality
right adrenal gland	UBERON:0001233	89.02	gold quality
body of uterus	UBERON:0009853	88.83	gold quality
muscle layer of sigmoid colon	UBERON:0035805	87.72	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.65	gold quality
left uterine tube	UBERON:0001303	87.46	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.03
E-MTAB-6379	no	474.41

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

162 targeting RIC3, 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-8485	100.00	77.57	4731
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267

Literature-anchored findings (GeneRIF, showing 24)

• the hric3 locus encodes for multiple transcripts, is likely to produce multiple hric3 isoforms, and hric3 is expressed in neurons and muscles, thus enabling its interactions with nicotinic acetylcholine receptors in vivo (PMID:12821669)
• ric-3 appears to be necessary for proper folding and/or assembly of alpha7 receptors in HEK293 cells (PMID:15504725)
• RIC-3 may play a role in 5-HT(3A) receptor folding, assembly, or transport to the cell surface (PMID:15809299)
• hRIC-3 can act as a specific regulator of alpha7 and 5-HT3 expression at different levels by increasing the number of mature receptors and facilitating its transport to the membrane (PMID:15927954)
• Mutations in the ric-3 gene affect maturation of nicotinic acetylcholine receptors. (PMID:17192664)
• both isoforms of RIC-3 play a role in determining 5-HT3 receptor composition. (PMID:17609200)
• Immunohistochemistry demonstrated the presence of RIC-3 in rat brain localized, in general, in places where alpha7 nAChRs were found. (PMID:18179477)
• When expressed in a human cell line, human RIC-3 enhances neuronal nicotinic acetylcholine receptor maturation more efficiently than Drosophila melanogaster RIC-3. (PMID:18208544)
• this review provides a brief history of RIC-3–REVIEW (PMID:18246096)
• we describe the generation and functional and pharmacological characterization of a Chinese hamster ovary (CHO)-K1 cell line co-expressing the human alpha7 nAChR and RIC-3 (PMID:18471073)
• The RIC-3e protein is functionally active and enables surface expression of mature alpha7-nAChRs in cell lines not otherwise permissive for the expression of this receptor. (PMID:18691158)
• RIC-3 exclusively enhances the surface expression of human homomeric 5-hydroxytryptamine type 3A (5-HT3A) receptors despite direct interactions with 5-HT3A, -C, -D, and -E subunits. (PMID:20522555)
• Xenopus laevis RIC-3 is more effective than either the homomeric human or C. elegans protein in chaperoning the expression of nematode nicotinic receptor ACR-16 in Xenopus oocytes. (PMID:22970690)
• RIC-3 gene rs1528133 variation was not found to be effective over any analyzed obesity related parameter, but associated with higher glycemic load, protein and fat eating behavior and antihypertensive drug use (PMID:23153976)
• RIC-3 differentially regulates assembly and expression of different nicotinic receptor subunits. These results also show that nicotine-mediated upregulation of alpha4beta2 receptors can be dynamically regulated by the presence of the chaperone, RIC-3. (PMID:23586521)
• expression of chaperones such as Ric-3 can influence proteins associating with alpha7-nAChRs (PMID:26258666)
• 5-HT3A-ICD is not only required but also sufficient for interaction with RIC-3 (PMID:27045630)
• RIC3 is a known chaperone of neuronal nicotinic acetylcholine receptor subunit alpha-7 (CHRNA7). (PMID:27055476)
• RIC3 mutations are not a common cause of PD in the French-Canadian and French populations. (PMID:28153381)
• Two RIC3 gene haplotypes of four variants: A-G-C-G, and C-A-C-A might relate to either protection against or increased susceptibility to PD in the Han Chinese population, respectively. (PMID:28606768)
• RIC3, the cholinergic anti-inflammatory pathway, and neuroinflammation. (PMID:32179243)
• RIC3 variants are not associated with Parkinson’s disease in large European, Latin American, or East Asian cohorts. (PMID:34538707)
• Deletion induced splicing in RIC3 drives nicotinic acetylcholine receptor regulation with implications for endoplasmic reticulum stress in human astrocytes. (PMID:36602087)
• Unraveling the molecular interactions between alpha7 nicotinic receptor and a RIC3 variant associated with backward speech. (PMID:38472514)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000101185
danio_rerio	ric3a	ENSDARG00000105549
mus_musculus	Ric3	ENSMUSG00000048330
rattus_norvegicus	Ric3	ENSRNOG00000014691
caenorhabditis_elegans		WBGENE00004363

Protein

Protein identifiers

Protein RIC-3 — Q7Z5B4 (reviewed: Q7Z5B4)

Alternative names: Resistant to inhibitor of cholinesterase 3

All UniProt accessions (6): A0A0S2Z607, A0A0S2Z6D3, Q7Z5B4, E9PK46, E9PKX8, E9PNI0

UniProt curated annotations — full annotation on UniProt →

Function. Molecular chaperone which facilitates proper subunit assembly and surface trafficking of alpha-7 (CHRNA7) and alpha-8 (CHRNA8) nicotinic acetylcholine receptors. May also promote functional expression of homomeric serotoninergic 5-HT3 receptors, and of heteromeric acetylcholine receptors alpha-3/beta-2, alpha-3/beta-4, alpha-4/beta-2 and alpha-4/beta-4.

Subunit / interactions. Monomer and homodimer. Interacts with CHRNA7, CHRNA3, CHRNA4, CHRNB2, CHRNB4 and HTR3A.

Subcellular location. Endoplasmic reticulum membrane Endoplasmic reticulum membrane. Golgi apparatus membrane.

Tissue specificity. Broadly expressed, with high levels in muscle, brain, heart, pancreas and testis. In the central nervous system, highest levels are detected in the cerebellum and pituitary gland. Over-expressed in brains from patients with bipolar disease or schizophrenia. Isoform 5 is predominantly expressed in the brain.

Domain organisation. The coiled-coil domain mediates transient homodimerization with other acetylcholine receptor-bound RIC3 molecules, promoting stepwise ACHR homomeric assembly at the membrane.

Similarity. Belongs to the ric-3 family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q7Z5B4-1	1, a	yes
Q7Z5B4-2	2, d
Q7Z5B4-3	3, c
Q7Z5B4-5	4, b
Q7Z5B4-6	5, e

RefSeq proteins (9): NP_001128581, NP_001193600, NP_001193601, NP_001333619, NP_001333620, NP_001333621, NP_001333622, NP_001333623, NP_078833 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026160	Ric3	Family
IPR032763	RIC3_N	Domain

Pfam: PF15361

UniProt features (24 total): splice variant 5, sequence variant 3, sequence conflict 3, region of interest 3, compositionally biased region 2, topological domain 2, signal peptide 1, chain 1, modified residue 1, cross-link 1, transmembrane region 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z5B4-F1	58.55	0.04

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): 202, 202

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 107 (showing top): GOBP_SYNAPTIC_TRANSMISSION_CHOLINERGIC, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION_TO_CELL_SURFACE, GOBP_CELL_CELL_SIGNALING, GOBP_PROTEIN_MATURATION, GOBP_REGULATION_OF_PROTEIN_LOCALIZATION_TO_CELL_SURFACE, GGAANCGGAANY_UNKNOWN, CCTGTGA_MIR513, GOBP_PROTEIN_FOLDING, GOBP_SYNAPTIC_SIGNALING, AACTTT_UNKNOWN, GOBP_PROTEIN_LOCALIZATION_TO_CELL_SURFACE, GOCC_NEURON_PROJECTION, GOMF_SIGNALING_RECEPTOR_BINDING, GOCC_SYNAPSE

GO Biological Process (6): positive regulation of cytosolic calcium ion concentration (GO:0007204), synaptic transmission, cholinergic (GO:0007271), protein localization to cell surface (GO:0034394), protein-containing complex assembly (GO:0065003), positive regulation of protein localization to cell surface (GO:2000010), protein folding (GO:0006457)

GO Molecular Function (3): acetylcholine receptor binding (GO:0033130), protein folding chaperone (GO:0044183), protein binding (GO:0005515)

GO Cellular Component (8): Golgi membrane (GO:0000139), endoplasmic reticulum membrane (GO:0005789), neuron projection (GO:0043005), neuronal cell body (GO:0043025), synapse (GO:0045202), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
endomembrane system	2
intracellular membrane-bounded organelle	2
regulation of biological quality	1
chemical synaptic transmission	1
intracellular protein localization	1
cellular component assembly	1
protein-containing complex organization	1
protein localization to cell surface	1
positive regulation of protein localization	1
regulation of protein localization to cell surface	1
cellular process	1
protein maturation	1
signaling receptor binding	1
molecular_function	1
protein folding	1
binding	1
Golgi apparatus	1
bounding membrane of organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
plasma membrane bounded cell projection	1
somatodendritic compartment	1
cell body	1
cell junction	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1014 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RIC3	HTR3A	P46098	938
RIC3	DEGS2	Q6QHC5	870
RIC3	UNC50	Q53HI1	858
RIC3	CHRNB4	P30926	755
RIC3	CHRNA4	P43681	751
RIC3	CHRNA3	P32297	662
RIC3	DNAJC13	O75165	652
RIC3	BCHE	P06276	631
RIC3	RAPSN	Q13702	620
RIC3	LMO1	P25800	593
RIC3	HTR2A	P28223	589
RIC3	TMEM230	Q96A57	583
RIC3	FBXO7	Q9Y3I1	573
RIC3	TMX3	Q96JJ7	572
RIC3	PTRHD1	Q6GMV3	572

IntAct

6 interactions, top by confidence:

A	B	Type	Score
CCAR2	CEP170	psi-mi:“MI:0914”(association)	0.640
RIC3	ATP9A	psi-mi:“MI:0914”(association)	0.530
RIC3	Klc1	psi-mi:“MI:0915”(physical association)	0.400
RIC3	CACNA1C	psi-mi:“MI:0915”(physical association)	0.370
RIC3	QSOX1	psi-mi:“MI:0914”(association)	0.350

BioGRID (83): VDAC3 (Affinity Capture-MS), PHB (Affinity Capture-MS), ERLIN2 (Affinity Capture-MS), ATP1A3 (Affinity Capture-MS), NCAPG2 (Affinity Capture-MS), ATP2A2 (Affinity Capture-MS), IPO7 (Affinity Capture-MS), HSPA8 (Affinity Capture-MS), DNAJC11 (Affinity Capture-MS), NCAPD3 (Affinity Capture-MS), SMC2 (Affinity Capture-MS), USP22 (Affinity Capture-MS), HMGCR (Affinity Capture-MS), PHB2 (Affinity Capture-MS), SLC30A5 (Affinity Capture-MS)

ESM2 similar proteins: A0A804C8T0, A4ZNR4, A4ZNR5, B2RX88, F7C1E2, O00165, O08623, O35387, O70367, O75829, O77770, P17404, P25686, P58340, Q03157, Q08E24, Q13501, Q15773, Q16626, Q29407, Q2KIE2, Q32KY3, Q3UIL6, Q4R992, Q5R491, Q5R4T3, Q5RBA5, Q5XIA0, Q64337, Q6AYN2, Q6BEG7, Q6IQ23, Q6PAQ9, Q7TNY7, Q7TSE9, Q7Z5B4, Q8BK03, Q8BPM6, Q8K3I4, Q8NFW9

Diamond homologs: Q0VFF9, Q7Z5B4, Q8BPM6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	1
Uncertain significance	261
Likely benign	189
Benign	20

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
1070074	NM_177972.3(TUB):c.256C>T (p.Gln86Ter)	Pathogenic
1075292	NM_177972.3(TUB):c.967C>T (p.Arg323Ter)	Pathogenic
1460462	NM_177972.3(TUB):c.781dup (p.Gln261fs)	Pathogenic
162490	NM_177972.3(TUB):c.1194_1195del (p.Arg398fs)	Pathogenic
2021852	NM_177972.3(TUB):c.1192_1211del (p.Arg398fs)	Pathogenic
860995	NM_177972.3(TUB):c.726dup (p.Pro243fs)	Pathogenic
3691480	NM_177972.3(TUB):c.565+1G>A	Likely pathogenic

SpliceAI

1918 predictions. Top by Δscore:

Variant	Effect	Δscore
11:8111136:ACCT:A	acceptor_loss	1.0000
11:8111138:C:CC	acceptor_gain	1.0000
11:8111138:C:G	acceptor_loss	1.0000
11:8126654:TTTAC:T	donor_loss	1.0000
11:8126655:TTA:T	donor_loss	1.0000
11:8126656:TA:T	donor_loss	1.0000
11:8126658:C:CT	donor_loss	1.0000
11:8126661:T:A	donor_gain	1.0000
11:8126809:T:C	acceptor_gain	1.0000
11:8138407:CCTCA:C	acceptor_gain	1.0000
11:8138410:C:CT	acceptor_gain	1.0000
11:8168862:TTA:T	donor_loss	1.0000
11:8168863:TA:T	donor_loss	1.0000
11:8168865:C:A	donor_loss	1.0000
11:8111134:TAAC:T	acceptor_gain	0.9900
11:8126653:GTTTA:G	donor_loss	0.9900
11:8126809:T:TC	acceptor_gain	0.9900
11:8137468:CTGG:C	acceptor_gain	0.9900
11:8138270:A:AC	donor_gain	0.9900
11:8138271:C:CC	donor_gain	0.9900
11:8138274:ATTTT:A	donor_gain	0.9900
11:8138411:A:C	acceptor_gain	0.9900
11:8138415:C:CT	acceptor_gain	0.9900
11:8168864:A:AC	donor_gain	0.9900
11:8168865:C:CC	donor_gain	0.9900
11:8168865:CCTT:C	donor_gain	0.9900
11:8126803:CTCTG:C	acceptor_gain	0.9800
11:8137377:CCT:C	donor_gain	0.9800
11:8137472:C:CC	acceptor_gain	0.9800
11:8138271:CTA:C	donor_gain	0.9800

AlphaMissense

2411 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:8140001:C:T	G106E	0.997
11:8140007:C:T	G104D	0.997
11:8137438:A:G	L154P	0.996
11:8126757:A:G	L191P	0.995
11:8137450:A:G	L150P	0.995
11:8139986:A:T	I111K	0.995
11:8140002:C:G	G106R	0.994
11:8140002:C:T	G106R	0.994
11:8140008:C:G	G104R	0.992
11:8139986:A:C	I111R	0.991
11:8139990:A:C	Y110D	0.989
11:8168950:C:G	G14R	0.989
11:8168950:C:T	G14R	0.989
11:8137421:C:G	A160P	0.988
11:8140011:A:C	Y103D	0.988
11:8139998:A:T	I107N	0.987
11:8140019:A:T	I100N	0.987
11:8168940:A:C	L17R	0.987
11:8168949:C:T	G14E	0.987
11:8139967:C:A	K117N	0.986
11:8139967:C:G	K117N	0.986
11:8140013:A:T	I102N	0.986
11:8168943:A:T	V16D	0.985
11:8137429:G:A	T157I	0.984
11:8139998:A:G	I107T	0.984
11:8126769:A:G	L187S	0.983
11:8168940:A:T	L17Q	0.983
11:8139990:A:G	Y110H	0.982
11:8126748:A:C	I194S	0.981
11:8137459:A:G	L147P	0.980

dbSNP variants (sampled 300 via entrez): RS1000006631 (11:8092818 G>A), RS1000036415 (11:8099076 G>A), RS1000119731 (11:8159799 T>A,C), RS1000142840 (11:8127381 A>T), RS1000146600 (11:8166009 G>A), RS1000148513 (11:8124328 C>A,T), RS1000166872 (11:8116009 A>G), RS1000172878 (11:8121477 A>G), RS1000231286 (11:8115606 G>A,C), RS1000255676 (11:8160163 T>C), RS1000259698 (11:8131836 G>A), RS1000295514 (11:8151211 A>C), RS1000331989 (11:8092551 A>G), RS1000387481 (11:8161843 TCC>T), RS1000391328 (11:8156669 T>C)

Disease associations

OMIM: gene MIM:610509 | disease phenotypes: MIM:616188

GenCC curated gene-disease

Disease	Classification	Inheritance
Parkinson disease	Limited	Autosomal dominant
movement disorder	Limited	Autosomal recessive

Mondo (4): retinal dystrophy and obesity (MONDO:0014522), inherited retinal dystrophy (MONDO:0019118), Parkinson disease (MONDO:0005180), movement disorder (MONDO:0005395)

Orphanet (2): Retinitis pigmentosa (Orphanet:791), OBSOLETE: Inherited retinal disorder (Orphanet:71862)

HPO phenotypes

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

HPO	Term
HP:0000556	Retinal dystrophy

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST005950_10	Body mass index x sex x age interaction (4df test)	6.000000e-11
GCST005951_51	Body mass index	8.000000e-11
GCST005953_4	Body mass index (age <50)	4.000000e-11
GCST006585_637	Blood protein levels	2.000000e-06
GCST010725_20	Malaria	4.000000e-69
GCST010725_33	Malaria	2.000000e-67
GCST010725_51	Malaria	1.000000e-55

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D009069	Movement Disorders	C10.228.662
D010300	Parkinson Disease	C10.228.140.079.862.500; C10.228.662.600.400; C10.574.928.750
D058499	Retinal Dystrophies	C11.768.585.658

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
terbufos	increases methylation	1
arsenite	increases methylation	1
sodium arsenite	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1
Arsenic	affects methylation	1
Vehicle Emissions	increases expression, increases abundance	1
Benzo(a)pyrene	decreases methylation	1
Doxorubicin	decreases expression	1
Fonofos	increases methylation	1
N-Nitrosopyrrolidine	decreases expression	1
Parathion	increases methylation	1
Testosterone	decreases expression	1
Theophylline	affects binding	1
Tobacco Smoke Pollution	decreases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1KI	PrecisION hnAChR alpha7/ric3-HEK	Transformed cell line	Female
CVCL_E2JB	HAP1 RIC3 (-) 2	Cancer cell line	Male
CVCL_E2JC	HAP1 RIC3 (-) 3	Cancer cell line	Male
CVCL_XS26	HAP1 RIC3 (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

339 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