PACRG

Summary

PACRG (parkin coregulated, HGNC:19152) is a protein-coding gene on chromosome 6q26, encoding Parkin coregulated gene protein (Q96M98). Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating.

This gene encodes a protein that is conserved across metazoans. In vertebrates, this gene is linked in a head-to-head arrangement with the adjacent parkin gene, which is associated with autosomal recessive juvenile Parkinson’s disease. These genes are co-regulated in various tissues and they share a bi-directional promoter. Both genes are associated with susceptibility to leprosy. The parkin co-regulated gene protein forms a large molecular complex with chaperones, including heat shock proteins 70 and 90, and chaperonin components. This protein is also a component of Lewy bodies in Parkinson’s disease patients, and it suppresses unfolded Pael receptor-induced neuronal cell death. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 135138 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 95 total — 9 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 1
• MANE Select transcript: NM_001080379

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19152
Approved symbol	PACRG
Name	parkin coregulated
Location	6q26
Locus type	gene with protein product
Status	Approved
Aliases	PARK2CRG, FLJ32724, Glup, HAK005771, BUG21, pf12
Ensembl gene	ENSG00000112530
Ensembl biotype	protein_coding
OMIM	608427
Entrez	135138

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000337019, ENST00000366888, ENST00000366889, ENST00000534958, ENST00000541974, ENST00000542669, ENST00000542936, ENST00000544266, ENST00000545186

RefSeq mRNA: 3 — MANE Select: NM_001080379 NM_001080378, NM_001080379, NM_152410

CCDS: CCDS43524, CCDS5284

Canonical transcript exons

ENST00000366888 — 5 exons

Exon	Start	End
ENSE00001442914	163314827	163315500
ENSE00002243099	162727974	162728391
ENSE00003575840	162814147	162814281
ENSE00003608527	163062150	163062321
ENSE00003685197	163089259	163089408

Expression profiles

Bgee: expression breadth ubiquitous, 197 present calls, max score 94.91.

FANTOM5 (CAGE): breadth broad, TPM avg 2.8700 / max 309.5807, expressed in 457 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
71083	1.4075	196
71085	0.8917	286
71086	0.3205	127
71082	0.2233	107
71084	0.0270	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	94.91	gold quality
right uterine tube	UBERON:0001302	94.53	gold quality
epithelium of bronchus	UBERON:0002031	94.06	gold quality
bronchus	UBERON:0002185	92.78	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.63	gold quality
left testis	UBERON:0004533	91.53	gold quality
right testis	UBERON:0004534	90.91	gold quality
testis	UBERON:0000473	89.87	gold quality
sperm	CL:0000019	89.33	gold quality
adenohypophysis	UBERON:0002196	88.40	gold quality
male germ cell	CL:0000015	88.01	gold quality
pituitary gland	UBERON:0000007	87.97	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.67	gold quality
mucosa of paranasal sinus	UBERON:0005030	87.32	gold quality
apex of heart	UBERON:0002098	86.52	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.50	gold quality
heart left ventricle	UBERON:0002084	85.32	gold quality
cardiac ventricle	UBERON:0002082	84.57	gold quality
epithelium of nasopharynx	UBERON:0001951	82.93	gold quality
nucleus accumbens	UBERON:0001882	82.89	gold quality
caudate nucleus	UBERON:0001873	82.11	gold quality
endothelial cell	CL:0000115	81.25	gold quality
hypothalamus	UBERON:0001898	80.99	gold quality
hindlimb stylopod muscle	UBERON:0004252	80.37	gold quality
prefrontal cortex	UBERON:0000451	80.30	gold quality
cortical plate	UBERON:0005343	79.81	gold quality
heart	UBERON:0000948	79.33	gold quality
right atrium auricular region	UBERON:0006631	79.01	gold quality
ventricular zone	UBERON:0003053	78.96	gold quality
putamen	UBERON:0001874	78.60	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	4609.74
E-GEOD-131882	yes	4535.66
E-CURD-114	yes	10.22
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

27 targeting PACRG, 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-1236-3P	99.94	68.04	1695
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-1284	99.67	73.56	1353
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-4524A-5P	99.57	71.73	1193
HSA-MIR-4524B-5P	99.57	71.68	1195
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-4999-5P	99.35	69.15	926
HSA-MIR-4796-5P	99.34	70.06	810
HSA-MIR-6719-3P	99.29	67.78	1387
HSA-MIR-3978	99.24	68.39	2201
HSA-MIR-2054	99.20	68.89	1699
HSA-MIR-3117-5P	99.04	67.93	618
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-455-3P	98.94	67.68	878
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-374B-3P	98.63	68.24	1360
HSA-MIR-4709-5P	98.51	67.25	1335
HSA-MIR-4457	98.09	67.12	1274
HSA-MIR-4708-5P	97.77	67.82	831
HSA-MIR-3190-3P	97.61	66.95	1406
HSA-MIR-219B-3P	97.31	66.96	672

Literature-anchored findings (GeneRIF, showing 20)

• PACRG is linked to parkin via a bi-directional promoter (PMID:12547187)
• Glup/PACRG forms a large molecular chaperone complex, suppresses cell death induced by accumulation of unfolded Pael receptor, facilitates the formation of Pael-R inclusions,and is a component of Lewy bodies in Parkinson’s disease (PMID:14532270)
• Variants in the regulatory region shared by PARK2 and PACRG therefore act as common risk factors for leprosy (PMID:14737177)
• mutation of PACRG plays little or no role in the development of early-onset parkinsonism (PMID:15925106)
• candidate tumor suppressor genes PARK2 and PACRG are epigenetically regulated in human leukemia, suggesting that abnormal methylation and regulation of PARK2 and PACRG may play a role in the pathogenesis and development of this hematological neoplasm (PMID:16287063)
• Suspected association of SNP’s with leprosy is not borne out in Indian population. (PMID:16391553)
• PACRG is regulated by the ubiquitin-proteasomal system and may play a role in the pathogenesis of Parkinson’s disease. (PMID:17590346)
• The observed features of genotypic distribution by PACRG marker point to the influence of the considered marker on the incidence of tuberculosis. (PMID:17722288)
• Thw results of this study suggested that point mutations in PACRG are not a common cause of EO-PD but haploinsufficiency for PACRG may be associated with disease. (PMID:19196541)
• Mutation of PACRG was not identified as a cause of male infertility, but variation in the promoter was demonstrated to be a risk factor associated with azoospermia. (PMID:19268936)
• PINK1, Omi/HtrA2 and parkin participate at different levels in mitochondrial quality control, converging through some overlapping and some distinct steps to maintain a common phenotype of healthy mitochondrial networks [REVIEW] (PMID:20012177)
• the association of polymorphisms rs9356058 and rs1040079 in gene PARK2/PACRG with leprosy (PMID:21816242)
• single nucleotide polymorphisms of PARK2 with leprosy susceptibility in Chinese population (PMID:22009144)
• Elevated levels of PACRG result in increased neuronal autophagy. (PMID:22652456)
• conducted high-density association mapping of PARK2/PACRG SNPs with leprosy and identified 69 SNPs significantly associated with leprosy in 198 single-case Vietnamese leprosy families (PMID:23052943)
• PARK2 and PACRG are commonly downregulated in clear-cell renal cell carcinoma and are associated with aggressive disease and poor clinical outcome. (PMID:23125027)
• Mapping of the PARK2 and PACRG gene regulatory region with 96 SNPs, with a resolution of 1 SNP per 1 Kb for PARK2 gene regulatory region in a North Indian population, showed an involvement of 11 SNPs in determining the susceptibility towards leprosy. (PMID:23861666)
• The parkin-coregulated gene product PACRG promotes TNF signaling by stabilizing LUBAC. (PMID:32019898)
• Associations of PRKN-PACRG SNPs and G x G and G x E interactions with the risk of hyperlipidaemia. (PMID:32747620)
• Crystal structure of human PACRG in complex with MEIG1 reveals roles in axoneme formation and tubulin binding. (PMID:33529594)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	pacrg	ENSDARG00000087556
mus_musculus	Pacrg	ENSMUSG00000037196
rattus_norvegicus	Pacrg	ENSRNOG00000068261
drosophila_melanogaster	CG17349	FBGN0032771
drosophila_melanogaster	CG15120	FBGN0034454
caenorhabditis_elegans		WBGENE00017122

Paralogs (1): PACRGL (ENSG00000163138)

Protein

Protein identifiers

Parkin coregulated gene protein — Q96M98 (reviewed: Q96M98)

Alternative names: Molecular chaperone/chaperonin-binding protein, PARK2 coregulated gene protein

All UniProt accessions (4): Q96M98, H0YFE8, H0YFW3, H0YGE0

UniProt curated annotations — full annotation on UniProt →

Function. Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating. Suppresses cell death induced by accumulation of unfolded Pael receptor (Pael-R, a substrate of Parkin). Facilitates the formation of inclusions consisting of Pael-R, molecular chaperones, protein degradation molecules and itself when proteasome is inhibited. May play an important role in the formation of Lewy bodies and protection of dopaminergic neurons against Parkinson disease.

Subunit / interactions. Microtubule inner protein component of sperm flagellar doublet microtubules. Forms a large molecular chaperone complex containing heat shock proteins 70 and 90 and chaperonin components. Interacts with STIP1, PRKN, GPR37, HSPA8, TCP1/CCT1, CCT2, CCT3, CCT4, CCT5, CCT6A, CCT7 and CCT8. Interacts with MEIG1.

Subcellular location. Cytoplasm. Cytoskeleton. Cilium axoneme. Flagellum axoneme.

Tissue specificity. Expressed in all immune tissues, spleen, lymph nodes, thymus, tonsils, leukocyte and bone marrow. Expressed also in heart, brain, skeletal muscle, kidney, lung and pancreas. Expressed in primary Schwann cells and very weakly by monocyte-derived macrophages the primary host cells of Mycobacterium leprae, the causative agent of leprosy. Component of Lewy bodies, intraneuronal inclusions found in the brain of Parkinson disease patients.

Polymorphism. Involved in susceptibility to leprosy (LPRS2) [MIM:607572]. LPRS2 is associated with polymorphisms in the 5’-regulatory region shared by the PRKN gene.

Miscellaneous. Linked to PRKN in a head-to-head arrangement on opposite DNA strands and share a common 5’-flanking promoter region. May be due to exon skipping.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96M98-1	1	yes
Q96M98-2	2

RefSeq proteins (3): NP_001073847, NP_001073848, NP_689623 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019399	Parkin_co-regulated_protein	Family

Pfam: PF10274

UniProt features (21 total): helix 15, sequence conflict 2, strand 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
6NEP	X-RAY DIFFRACTION	2.1
6NDU	X-RAY DIFFRACTION	2.1
6UCC	X-RAY DIFFRACTION	2.6
7UNG	ELECTRON MICROSCOPY	3.6
8J07	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96M98-F1	77.35	0.54

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 156 (showing top): TGCGCANK_UNKNOWN, GOBP_MALE_GAMETE_GENERATION, AAAYRNCTG_UNKNOWN, GOBP_CELLULAR_RESPONSE_TO_TOPOLOGICALLY_INCORRECT_PROTEIN, WEI_MYCN_TARGETS_WITH_E_BOX, CAIRO_HEPATOBLASTOMA_CLASSES_DN, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_CILIUM_MOVEMENT, chr6q26, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, CYTAGCAAY_UNKNOWN, GOMF_G_PROTEIN_COUPLED_RECEPTOR_BINDING, GOMF_ACTIN_BINDING

GO Biological Process (4): spermatid development (GO:0007286), intracellular protein localization (GO:0008104), flagellated sperm motility (GO:0030317), cellular response to unfolded protein (GO:0034620)

GO Molecular Function (10): G protein-coupled receptor binding (GO:0001664), actin binding (GO:0003779), Hsp70 protein binding (GO:0030544), heat shock protein binding (GO:0031072), ubiquitin protein ligase binding (GO:0031625), alpha-tubulin binding (GO:0043014), beta-tubulin binding (GO:0048487), protein-folding chaperone binding (GO:0051087), Hsp90 protein binding (GO:0051879), protein binding (GO:0005515)

GO Cellular Component (17): manchette (GO:0002177), nucleus (GO:0005634), cytosol (GO:0005829), axonemal microtubule (GO:0005879), vesicle (GO:0031982), neuron projection (GO:0043005), cell body (GO:0044297), sperm midpiece (GO:0097225), glial cell projection (GO:0097386), axonemal B tubule inner sheath (GO:0160112), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cilium (GO:0005929), membrane (GO:0016020), motile cilium (GO:0031514), sperm flagellum (GO:0036126), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	8
plasma membrane bounded cell projection	3
heat shock protein binding	2
protein binding	2
tubulin binding	2
membrane-bounded organelle	2
germ cell development	1
spermatid differentiation	1
macromolecule localization	1
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
response to unfolded protein	1
cellular response to topologically incorrect protein	1
signaling receptor binding	1
cytoskeletal protein binding	1
protein-folding chaperone binding	1
ubiquitin-like protein ligase binding	1
binding	1
microtubule cytoskeleton	1
intracellular membrane-bounded organelle	1
cytoplasm	1
cytoplasmic microtubule	1
axoneme	1
sperm flagellum	1
A axonemal microtubule	1
axonemal microtubule doublet inner sheath	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
intraciliary transport particle	1
cilium	1
9+2 motile cilium	1

Protein interactions and networks

STRING

2477 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PACRG	PRKN	O60260	878
PACRG	QKI	Q96PU8	663
PACRG	MEIG1	Q5JSS6	596
PACRG	EFHC1	Q5JVL4	583
PACRG	CCDC122	Q5T0U0	583
PACRG	MORN3	Q6PF18	575
PACRG	TUBB2B	Q9BVA1	509
PACRG	ENKUR	Q8TC29	509
PACRG	GALP	Q9UBC7	507
PACRG	GPR37	O15354	496
PACRG	CCDC40	Q4G0X9	496
PACRG	STK36	Q9NRP7	492
PACRG	CCDC39	Q9UFE4	486
PACRG	FBXO33	Q7Z6M2	478
PACRG	RTTN	Q86VV8	478

IntAct

5 interactions, top by confidence:

A	B	Type	Score
PACRG	MAD1L1	psi-mi:“MI:0915”(physical association)	0.400
PACRG	KLHL36	psi-mi:“MI:0915”(physical association)	0.400
CCDC40	PACRG	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (38): KLHL36 (Affinity Capture-MS), PACRG (Synthetic Growth Defect), STIP1 (Affinity Capture-MS), KLHL36 (Affinity Capture-MS), PACRG (Affinity Capture-MS), PACRG (Affinity Capture-RNA), PACRG (Biochemical Activity), PACRG (Proximity Label-MS), MEIG1 (Two-hybrid), MAD1L1 (Proximity Label-MS), PACRG (Affinity Capture-Western), PACRG (Affinity Capture-Western), PACRG (Co-fractionation), KLHL36 (Affinity Capture-MS), PACRG (Affinity Capture-RNA)

ESM2 similar proteins: A0A0B4K859, A1Z7L1, A1ZBE8, A5D8W1, A8XSV3, B0CM26, B0VXE6, F4JHT3, F4JY37, F6S215, O74447, P25355, P49815, P49816, P78527, P97313, P97357, Q03124, Q03280, Q14156, Q15573, Q19317, Q21106, Q571H0, Q5M6W3, Q5SPP5, Q5WNI9, Q61037, Q61QK6, Q641A2, Q6DFV1, Q6PQD5, Q6ZQ18, Q8BG67, Q8BH53, Q8C3Y4, Q8H0T4, Q8IGJ0, Q8QGX4, Q8WN22

Diamond homologs: A5PK71, Q96M98, Q9DAK2, A0A096LPI5, A6NIU2, A6NJG6, P51957, Q5H9K5, Q5T7P6, Q8IV13, Q8N2A0, Q8N9N2, Q96T75, Q9BUA6, Q9UHC9, F2Z398, Q68CZ1, Q92918, Q09FC8, Q8TDM0, Q8VED2, Q96MD7, Q9NUP1

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
PRKN	“down-regulates quantity by destabilization”	PACRG	polyubiquitination
HSPA1A	“up-regulates quantity by stabilization”	PACRG	binding
HSPA1B	“up-regulates quantity by stabilization”	PACRG	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	1
Uncertain significance	65
Likely benign	9
Benign	5

Top pathogenic / likely-pathogenic (10)

Variant ID	HGVS	Classification
1460158	NC_000006.11:g.(?162683537)(163148700_?)del	Pathogenic
1705255	NC_000006.11:g.(162683798_162864341)_(162864506_163148693)dup	Pathogenic
1708184	GRCh37/hg19 6q25.3-27(chr6:157318401-165233548)x1	Pathogenic
3062882	GRCh37/hg19 6q26(chr6:162899570-163540127)x1	Pathogenic
3246174	NC_000006.11:g.(?163148674)(163148700_?)del	Pathogenic
3768468	NC_000006.11:g.(162683798_162864341)_(162864506_163148693)del	Pathogenic
4279141	GRCh37/hg19 6q26(chr6:162932944-163449996)x1	Pathogenic
7049	NM_013988.2(PARK2):c.(8_8)_(171_171)+180544del	Pathogenic
7053	NM_004562.3(PRKN):c.7+1G>T	Pathogenic
545336	NC_000006.12:g.(?162609404)(162813090_?)del	Likely pathogenic

SpliceAI

4502 predictions. Top by Δscore:

Variant	Effect	Δscore
6:162731035:T:G	donor_gain	1.0000
6:162814140:A:AG	acceptor_gain	1.0000
6:162814142:TTAA:T	acceptor_loss	1.0000
6:162814144:AAG:A	acceptor_gain	1.0000
6:162814145:A:AT	acceptor_loss	1.0000
6:162814146:GGT:G	acceptor_gain	1.0000
6:162814146:GGTGA:G	acceptor_gain	1.0000
6:162906696:TTAC:T	donor_gain	1.0000
6:163062142:A:AG	acceptor_gain	1.0000
6:163062143:C:G	acceptor_gain	1.0000
6:163062145:TTCA:T	acceptor_loss	1.0000
6:163062147:CA:C	acceptor_loss	1.0000
6:163062148:A:AG	acceptor_gain	1.0000
6:163062149:G:GC	acceptor_gain	1.0000
6:163062149:GGT:G	acceptor_gain	1.0000
6:163062149:GGTA:G	acceptor_gain	1.0000
6:163062318:AAAAG:A	donor_loss	1.0000
6:163062319:AAA:A	donor_gain	1.0000
6:163062319:AAAGT:A	donor_loss	1.0000
6:163062320:AA:A	donor_gain	1.0000
6:163062320:AAG:A	donor_loss	1.0000
6:163062321:AGTA:A	donor_loss	1.0000
6:163062322:G:GG	donor_gain	1.0000
6:163062323:T:A	donor_loss	1.0000
6:163062324:AAGT:A	donor_loss	1.0000
6:163089404:GAATG:G	donor_gain	1.0000
6:163089406:ATGGT:A	donor_loss	1.0000
6:163089409:G:C	donor_loss	1.0000
6:163089409:G:GG	donor_gain	1.0000
6:163089410:T:G	donor_loss	1.0000

AlphaMissense

1691 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:162728359:T:C	F42L	0.999
6:162728361:C:A	F42L	0.999
6:162728361:C:G	F42L	0.999
6:162814276:T:A	W96R	0.999
6:162814276:T:C	W96R	0.999
6:162814278:G:C	W96C	0.998
6:162814278:G:T	W96C	0.998
6:163089319:T:C	L175P	0.998
6:162814277:G:C	W96S	0.997
6:163062184:T:C	L109P	0.997
6:163062201:G:T	G115W	0.997
6:163062202:G:A	G115E	0.997
6:163062238:C:A	A127D	0.997
6:163062304:T:C	L149P	0.997
6:163062201:G:A	G115R	0.996
6:163062201:G:C	G115R	0.996
6:163062246:G:A	G130R	0.996
6:163062246:G:C	G130R	0.996
6:163062262:T:C	L135P	0.996
6:163089301:T:C	L169P	0.996
6:163089310:T:C	L172P	0.996
6:163314899:T:C	L268P	0.996
6:162814205:T:C	F72S	0.994
6:163062205:T:C	L116P	0.994
6:163062247:G:A	G130E	0.994
6:163062316:T:A	I153K	0.994
6:163089376:T:C	L194P	0.994
6:162728360:T:C	F42S	0.993
6:163062304:T:A	L149H	0.993
6:163089274:G:C	R160P	0.993

dbSNP variants (sampled 300 via entrez): RS1000001075 (6:162952738 T>G), RS1000005591 (6:162774194 G>A), RS1000011694 (6:163268117 T>C), RS1000025698 (6:163164685 C>T), RS1000026136 (6:162821835 C>G,T), RS1000027038 (6:163276657 T>C), RS1000029916 (6:163198856 C>T), RS1000034658 (6:163093827 G>A,T), RS1000038127 (6:163038609 T>C,G), RS1000043931 (6:163258657 T>G), RS1000044696 (6:162815540 G>A), RS1000058122 (6:163276385 C>T), RS1000065964 (6:163274494 G>A), RS1000066464 (6:163132669 A>G), RS1000067396 (6:163237976 C>A)

Disease associations

OMIM: gene MIM:608427 | disease phenotypes: MIM:600116, MIM:181500, MIM:168601

GenCC curated gene-disease

Mondo (5): autosomal recessive juvenile Parkinson disease 2 (MONDO:0010820), young-onset Parkinson disease (MONDO:0017279), schizophrenia (MONDO:0005090), lung adenocarcinoma (MONDO:0005061), autosomal dominant Parkinson disease 1 (MONDO:0008200)

Orphanet (3): Young-onset Parkinson disease (Orphanet:2828), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140), NON RARE IN EUROPE: Adenocarcinoma of the lung (Orphanet:415268)

HPO phenotypes

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

HPO	Term
HP:0100753	Schizophrenia

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST003264_1078	Post bronchodilator FEV1/FVC ratio	4.000000e-06
GCST003264_1087	Post bronchodilator FEV1/FVC ratio	4.000000e-06
GCST005044_1	Primary vesicoureteric reflux	3.000000e-09
GCST007220_1	Schizophrenia and type 2 diabetes	5.000000e-09
GCST009191_2	Paracentral lobule volume	3.000000e-06
GCST010241_325	Apolipoprotein A1 levels	2.000000e-08
GCST010242_143	HDL cholesterol levels	4.000000e-12

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004713	FEV/FVC ratio
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C566823	Parkinson Disease, Familial, Type 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation, increases methylation	4
Valproic Acid	increases expression, affects expression, decreases methylation	3
Aflatoxin B1	affects methylation, decreases expression, decreases methylation, increases methylation	3
Smoke	decreases expression, increases abundance, increases expression	2
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	decreases methylation	1
sodium arsenite	affects methylation	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	decreases methylation	1
epoxomicin	decreases expression	1
Sunitinib	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects methylation	1
Atrazine	increases expression	1
Methapyrilene	increases methylation	1
Tobacco Smoke Pollution	decreases expression	1
Okadaic Acid	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TB86	HAP1 PACRG (-) 1	Cancer cell line	Male
CVCL_XR31	HAP1 PACRG (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety