PAQR3

Summary

PAQR3 (progestin and adipoQ receptor family member 3, HGNC:30130) is a protein-coding gene on chromosome 4q21.21, encoding Progestin and adipoQ receptor family member 3 (Q6TCH7). Golgi-scaffold protein which modulates its interactors acitivies by anchoring them to the Golgi apparatus.

This gene encodes a seven-transmembrane protein localized in the Golgi apparatus in mammalian cells. The encoded protein belongs to the progestin and adipoQ receptor (PAQR) family. This protein functions as a tumor suppressor by inhibiting the Raf/MEK/ERK signaling cascade. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 152559 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 34 total
• MANE Select transcript: NM_001040202

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30130
Approved symbol	PAQR3
Name	progestin and adipoQ receptor family member 3
Location	4q21.21
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000163291
Ensembl biotype	protein_coding
OMIM	614577
Entrez	152559

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 6 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined, 2 retained_intron, 2 protein_coding

ENST00000342820, ENST00000395594, ENST00000503343, ENST00000505715, ENST00000505735, ENST00000508599, ENST00000511594, ENST00000512299, ENST00000512733, ENST00000512760, ENST00000515541, ENST00000515853, ENST00000956603

RefSeq mRNA: 3 — MANE Select: NM_001040202 NM_001040202, NM_001350105, NM_001350106

CCDS: CCDS34020

Canonical transcript exons

ENST00000512733 — 6 exons

Exon	Start	End
ENSE00001258993	78935121	78935283
ENSE00001522204	78939040	78939438
ENSE00002042550	78911878	78920681
ENSE00003480793	78930170	78930325
ENSE00003565767	78926521	78926718
ENSE00003693608	78923857	78923947

Expression profiles

Bgee: expression breadth ubiquitous, 269 present calls, max score 95.11.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.7375 / max 155.8396, expressed in 1759 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
52734	12.8450	1755
52732	0.8095	302
52733	0.0830	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	95.11	gold quality
jejunal mucosa	UBERON:0000399	92.12	gold quality
male germ cell	CL:0000015	92.07	gold quality
right testis	UBERON:0004534	91.66	gold quality
left testis	UBERON:0004533	91.34	gold quality
cortical plate	UBERON:0005343	91.34	gold quality
ganglionic eminence	UBERON:0004023	91.08	gold quality
testis	UBERON:0000473	90.69	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.12	gold quality
upper leg skin	UBERON:0004262	89.69	gold quality
ventricular zone	UBERON:0003053	89.63	gold quality
choroid plexus epithelium	UBERON:0003911	89.10	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.09	gold quality
Brodmann (1909) area 23	UBERON:0013554	88.76	gold quality
primary visual cortex	UBERON:0002436	88.42	gold quality
lower esophagus muscularis layer	UBERON:0035833	88.13	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.10	gold quality
lower esophagus	UBERON:0013473	88.04	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	87.89	gold quality
cerebellar hemisphere	UBERON:0002245	87.34	gold quality
cerebellar cortex	UBERON:0002129	87.26	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	87.02	gold quality
secondary oocyte	CL:0000655	86.95	gold quality
Brodmann (1909) area 9	UBERON:0013540	86.54	gold quality
mucosa of stomach	UBERON:0001199	86.30	gold quality
caudate nucleus	UBERON:0001873	86.24	gold quality
endothelial cell	CL:0000115	86.09	gold quality
prefrontal cortex	UBERON:0000451	85.91	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	85.82	gold quality
cerebellum	UBERON:0002037	85.57	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.90

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 35)

• reveal a paradigm of spatial regulation of Raf kinase by RKTG via sequestrating Raf-1 to the Golgi apparatus and thereby inhibiting the ERK signaling pathway. (PMID:17724343)
• RKTG may play a suppressive role in human melanoma that harbors an oncogenic B-Raf mutation via its antagonistic action on B-Raf. (PMID:18515281)
• Analysis in detail of the topology and functional domains of RKTG (Raf kinase trapping to Golgi). (PMID:18547165)
• Data show that adiponectin functions as an agonist of PAQR3. (PMID:19519172)
• RKTG can modulate GPCR signaling through sequestering G betagamma to the Golgi apparatus and thereby attenuating the functions of G betagamma. (PMID:19884349)
• Loss of PAQR3 is associated with tumorigenesis of colorectal cancers. (PMID:22828136)
• PAQR3 is markedly down-regulated in human gastric cancers. PAQR3 expression level is closely associated with the progression and metastasis of gastric cancers (PMID:24799462)
• PAQR3 may play an important role in the progression of hepatocellular carcinoma and serve as a potential candidate for the targeted therapy of hepatocellular carcinoma (PMID:25310770)
• PAQR3 might act as a tumor suppressor in osteosarcoma. (PMID:25510670)
• PAQR3 (progestin and adipoQ receptors member 3), a tumour suppressor specifically localized in the Golgi apparatus, negatively regulates H3K4 trimethylation (H3K4me3). (PMID:25706881)
• Our data indicate that PAQR3 functions as a tumor suppressor in the development of human breast cancers. (PMID:25900239)
• DDB2 is involved in ubiquitination and degradation of PAQR3 in gastric cancer cells. (PMID:26205499)
• PAQR3 plays a tumor suppressive role in laryngeal squamous cell carcinoma (PMID:26232324)
• PAQR3 regulates cholesterol homeostasis by anchoring Scap/SREBP to the Golgi and disruption of such function reduces cholesterol biosynthesis. (PMID:26311497)
• A novel role for the newly characterized, Golgi-localized PAQR3 in regulating heterotrimeric G-proteins at the non-canonical subcellular location of the Golgi. (PMID:26327583)
• findings not only pinpoint that Twist1 mediates the modulatory function of PAQR3 on EMT and metastasis but also suggest that targeting Twist1 is a promising strategy to control metastasis of tumors with downregulation of PAQR3 (PMID:26905590)
• our study pinpoints that PAQR3 functions as an adaptor protein to promote Nrf2-Keap1 complex formation, thereby modulating the Nrf2-Keap2 pathway and playing an important role in controlling antioxidant response of the cell (PMID:27212020)
• our results suggested that the aberrant methylation of PAQR3 underlies its downregulation in breast cancer and our data indicated that epigenetic silencing of PAQR3 gene expression by promoter hypermethylation may play an important role in breast cancer (PMID:27461225)
• This finding reveals a new mode of regulation of mTORC1 signaling and autophagy by PAQR3 in response to alterations of amino acids. (PMID:28214587)
• The expression of PAQR3 protein significantly decreased in lung cancer. (PMID:28442015)
• Data suggest that expression of PAQR3 is down-regulated in glioma tissues and cell lines; PAQR3 overexpression suppresses cell migration of glioma cells, suppresses invasivness of glioma in xenograft experiments, and prevents epithelial-mesenchymal transition. (PMID:28528182)
• we demonstrated that overexpression of PAQR3 suppresses cell proliferation, migration, and invasion in esophageal cancer in vitro and in vivo. (PMID:28548040)
• Low expression of PAQR3 is associated with gastric cancer metastasis. (PMID:28560431)
• PAQR3 is epigenetically silenced in esophageal squamous cell carcinoma (ESCC) and restoration of PAQR3 suppresses the aggressive phenotype of ESCC cells (PMID:28802234)
• that PAQR3 can be a promising methylation marker candidate for the detection and monitoring of prostate cancer (PMID:29122400)
• Ubiquitination modification through the coordinated action of PAQR3 with HUWE1 plays a crucial role in regulating the activity of hepatic PPARalpha in response to starvation. (PMID:29331071)
• Silencing of PAQR3 suppresses extracellular matrix accumulation in high glucose-stimulated human glomerular mesangial cells via PI3K/AKT signaling pathway (PMID:29787774)
• PAQR3 might regulate the phosphorylation of FoxO1 and the expressions of GCK and LDLR through NF-kappaB pathway, thereby regulating the glucose and lipid metabolism disorders induced by insulin resistance. (PMID:31095939)
• PAQR3 suppresses the growth of non-small cell lung cancer cells via modulation of EGFR-mediated autophagy. (PMID:31448672)
• Associations of the BRAF V600E Mutation and PAQR3 Protein Expression with Papillary Thyroid Carcinoma Clinicopathological Features. (PMID:31758408)
• MiR-15b facilitates breast cancer progression via repressing tumor suppressor PAQR3. (PMID:32016977)
• PAQR3 inhibits proliferation and aggravates ferroptosis in acute lymphoblastic leukemia through modulation Nrf2 stability. (PMID:33955706)
• Circular RNA hsa_circ_0043280 inhibits cervical cancer tumor growth and metastasis via miR-203a-3p/PAQR3 axis. (PMID:34588429)
• Golgi scaffold protein PAQR3 as a candidate suppressor of gastric cardia adenocarcinoma via regulating TGF-beta/Smad pathway. (PMID:35870178)
• Systematic pan-cancer analyses of the potential function of the Golgi scaffold protein PAQR3. (PMID:38321173)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	paqr3a	ENSDARG00000017703
danio_rerio	paqr3b	ENSDARG00000044253
mus_musculus	Paqr3	ENSMUSG00000055725
rattus_norvegicus	Paqr3	ENSRNOG00000002035
drosophila_melanogaster	CG7530	FBGN0038256
caenorhabditis_elegans		WBGENE00013457

Paralogs (10): ADIPOR2 (ENSG00000006831), MMD (ENSG00000108960), MMD2 (ENSG00000136297), PAQR5 (ENSG00000137819), ADIPOR1 (ENSG00000159346), PAQR6 (ENSG00000160781), PAQR4 (ENSG00000162073), PAQR8 (ENSG00000170915), PAQR7 (ENSG00000182749), PAQR9 (ENSG00000188582)

Protein

Protein identifiers

Progestin and adipoQ receptor family member 3 — Q6TCH7 (reviewed: Q6TCH7)

Alternative names: Progestin and adipoQ receptor family member III, Raf kinase trapping to Golgi

All UniProt accessions (3): D6RDU4, F8W784, Q6TCH7

UniProt curated annotations — full annotation on UniProt →

Function. Golgi-scaffold protein which modulates its interactors acitivies by anchoring them to the Golgi apparatus. Functions as a spatial regulator of RAF1 kinase by sequestrating it to the Golgi apparatus. Acts as a positive regulator of cholesterol biosynthesis by mediating the anchoring of the SCAP:SREBP complex in the Golgi apparatus, thereby promoting SCAP:SREBF2 complex formation, potentiating SREBF2 and SREBF1 processing and enhancing lipid synthesis. Also regulates PPARA and PPARG functions by mediating their interaction with E3 ubiquitin ligases, such as STUB1 or HUWE1, leading to their polyubiquitination and proteasome-mediated degradation.

Subunit / interactions. Interacts with SCAP and SREBF2; the interactions are direct, increase in low cholesterol conditions and tether SCAP:SREBP complex to the Golgi apparatus. Interaction with SCAP is mutually exclusive with INSIG1. In hepatocytes, interacts with PPARA and HUWE1; the interactions promote PPARA poylubiquitination and HUWE1-mediated degradation. In macrophages, interacts with PPARG and STUB1; the interactions promote PPARG poylubiquitination and STUB1-mediated degradation.

Subcellular location. Golgi apparatus membrane.

Tissue specificity. Widely expressed in a range of tissues.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the ADIPOR family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q6TCH7-1	1	yes
Q6TCH7-2	2
Q6TCH7-3	3
Q6TCH7-4	4

RefSeq proteins (3): NP_001035292, NP_001337034, NP_001337035 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004254	AdipoR/HlyIII-related	Family

Pfam: PF03006

UniProt features (26 total): topological domain 8, transmembrane region 7, region of interest 4, splice variant 4, sequence conflict 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6TCH7-F1	89.51	0.83

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5675221	Negative regulation of MAPK pathway

MSigDB gene sets: 225 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, GOBP_NEGATIVE_REGULATION_OF_MAP_KINASE_ACTIVITY, ACTACCT_MIR196A_MIR196B, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_NEGATIVE_REGULATION_OF_KINASE_ACTIVITY, GOBP_PEPTIDYL_SERINE_MODIFICATION, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, TATTATA_MIR374, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOBP_NEUROGENESIS

GO Biological Process (13): negative regulation of protein phosphorylation (GO:0001933), negative regulation of neuron projection development (GO:0010977), positive regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032436), negative regulation of peptidyl-serine phosphorylation (GO:0033137), protein localization to Golgi apparatus (GO:0034067), negative regulation of peroxisome proliferator activated receptor signaling pathway (GO:0035359), negative regulation of MAP kinase activity (GO:0043407), positive regulation of cholesterol biosynthetic process (GO:0045542), positive regulation of SREBP signaling pathway (GO:2000640), NLS-bearing protein import into nucleus (GO:0006607), peroxisome proliferator activated receptor signaling pathway (GO:0035357), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), protein maturation (GO:0051604)

GO Molecular Function (4): protein-membrane adaptor activity (GO:0043495), ubiquitin-like ligase-substrate adaptor activity (GO:1990756), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (3): Golgi membrane (GO:0000139), Golgi apparatus (GO:0005794), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
RAF/MAP kinase cascade	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of protein phosphorylation	1
protein phosphorylation	1
negative regulation of protein modification process	1
negative regulation of phosphorylation	1
regulation of neuron projection development	1
neuron projection development	1
negative regulation of cell projection organization	1
regulation of proteasomal ubiquitin-dependent protein catabolic process	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
positive regulation of proteasomal protein catabolic process	1
positive regulation of ubiquitin-dependent protein catabolic process	1
negative regulation of protein phosphorylation	1
peptidyl-serine phosphorylation	1
regulation of peptidyl-serine phosphorylation	1
protein localization to organelle	1
peroxisome proliferator activated receptor signaling pathway	1
regulation of peroxisome proliferator activated receptor signaling pathway	1
negative regulation of intracellular signal transduction	1
MAP kinase activity	1
regulation of MAP kinase activity	1
negative regulation of MAPK cascade	1
negative regulation of protein serine/threonine kinase activity	1
cholesterol biosynthetic process	1
regulation of cholesterol biosynthetic process	1
positive regulation of cholesterol metabolic process	1
positive regulation of sterol biosynthetic process	1
positive regulation of alcohol biosynthetic process	1
SREBP signaling pathway	1
positive regulation of intracellular signal transduction	1
regulation of SREBP signaling pathway	1
protein import into nucleus	1
nuclear receptor-mediated signaling pathway	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
gene expression	1
protein metabolic process	1
protein-macromolecule adaptor activity	1
enzyme-substrate adaptor activity	1
binding	1
cation binding	1

Protein interactions and networks

STRING

688 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PAQR3	MMD	Q15546	762
PAQR3	ATG14	Q6ZNE5	723
PAQR3	ADIPOQ	Q15848	643
PAQR3	MMD2	Q8IY49	634
PAQR3	SCAP	Q12770	587
PAQR3	SUCLG2	Q96I99	527
PAQR3	BECN1	Q14457	504
PAQR3	PIK3C3	Q8NEB9	493
PAQR3	RBBP5	Q15291	481
PAQR3	PAQR9	Q6ZVX9	467
PAQR3	DUSP19	Q8WTR2	446
PAQR3	PAQR6	Q6TCH4	437
PAQR3	ASH2L	Q9UBL3	421
PAQR3	ADIPOR1	Q96A54	383
PAQR3	ADIPOR2	Q86V24	383

IntAct

9 interactions, top by confidence:

A	B	Type	Score
RAF1	MAP2K1	psi-mi:“MI:0914”(association)	0.960
PAQR3	RAF1	psi-mi:“MI:0915”(physical association)	0.580
AVPR2	GXYLT2	psi-mi:“MI:0914”(association)	0.350
C5AR1	TCAF2	psi-mi:“MI:0914”(association)	0.350
NRSN1	FAM171A2	psi-mi:“MI:0914”(association)	0.350
GPR182	SLC12A8	psi-mi:“MI:0914”(association)	0.350
PAQR3	AGFG1	psi-mi:“MI:0914”(association)	0.350

BioGRID (42): DDB2 (Affinity Capture-Western), PAQR3 (Affinity Capture-Western), DDB2 (Co-localization), DDB2 (Reconstituted Complex), PAQR3 (Affinity Capture-Western), TWIST1 (Affinity Capture-Western), PAQR3 (Affinity Capture-Western), BTRC (Affinity Capture-Western), BTRC (Reconstituted Complex), TWIST1 (Co-localization), NFE2L2 (Affinity Capture-Western), KEAP1 (Affinity Capture-Western), PAQR3 (Affinity Capture-Western), PAQR3 (Affinity Capture-Western), PAQR3 (Affinity Capture-Western)

ESM2 similar proteins: A0JNC1, A4IFN5, A6QL84, B1H3H9, B2LYG4, D3ZEH5, O08650, O35052, O95674, P48651, P59266, P98191, Q00576, Q0JR55, Q0V9V2, Q10PI5, Q17QZ3, Q1LZA0, Q2KHY9, Q5F3L7, Q5PQL5, Q5QJU3, Q5RBJ7, Q5ZM65, Q6I628, Q6IQ69, Q6NQI8, Q6PHN7, Q6TCG8, Q6TCH7, Q803C9, Q80ZE4, Q865K8, Q86WK9, Q8BFQ2, Q8BWB6, Q8CIF6, Q8IY49, Q8N6M3, Q8NBD8

Diamond homologs: A8WZU4, Q03419, Q09749, Q09910, Q12442, Q6ETK9, Q6TCH7, Q753H5, Q86V24, Q8BQS5, Q91VH1, Q93ZH9, Q94177, Q96A54, Q9SVF3, Q9SZG0, Q9VCY8, Q9ZUH8, Q07959, Q6TCG8, Q75F81, B7F9G7, Q10PI5, Q6TCG2, Q6TCG5, Q6TCH4, Q6ZVX9, Q84N34, Q8N4S7

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
AMPK	“up-regulates activity”	PAQR3	phosphorylation
PAQR3	“up-regulates activity”	“Vps34 Complex I”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1432 predictions. Top by Δscore:

Variant	Effect	Δscore
4:78920596:CA:C	donor_gain	1.0000
4:78926516:CCTA:C	donor_loss	1.0000
4:78926517:CTAC:C	donor_loss	1.0000
4:78926518:TA:T	donor_loss	1.0000
4:78926520:C:CT	donor_loss	1.0000
4:78926714:CAGTA:C	acceptor_gain	1.0000
4:78926715:AGTA:A	acceptor_gain	1.0000
4:78926716:GTA:G	acceptor_gain	1.0000
4:78926716:GTACT:G	acceptor_gain	1.0000
4:78926717:TA:T	acceptor_gain	1.0000
4:78926717:TACTA:T	acceptor_loss	1.0000
4:78926718:AC:A	acceptor_loss	1.0000
4:78926719:C:CC	acceptor_gain	1.0000
4:78930165:CTT:C	donor_loss	1.0000
4:78930166:TTA:T	donor_loss	1.0000
4:78930167:TACGT:T	donor_loss	1.0000
4:78930168:A:AC	donor_gain	1.0000
4:78930168:A:AT	donor_loss	1.0000
4:78930169:C:A	donor_loss	1.0000
4:78930169:C:CT	donor_gain	1.0000
4:78930169:CG:C	donor_gain	1.0000
4:78930169:CGTT:C	donor_gain	1.0000
4:78930198:C:CA	donor_gain	1.0000
4:78930321:CAGAC:C	acceptor_gain	1.0000
4:78939037:TAC:T	donor_loss	1.0000
4:78939038:A:C	donor_loss	1.0000
4:78917877:GATTC:G	acceptor_gain	0.9900
4:78917878:ATTCT:A	acceptor_gain	0.9900
4:78920628:C:CT	donor_gain	0.9900
4:78920629:T:TT	donor_gain	0.9900

AlphaMissense

2020 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:78930214:C:G	G154R	0.999
4:78930234:C:T	G147E	0.999
4:78930235:C:G	G147R	0.999
4:78930235:C:T	G147R	0.999
4:78930243:T:A	D144V	0.999
4:78930243:T:G	D144A	0.999
4:78930256:A:G	W140R	0.999
4:78930256:A:T	W140R	0.999
4:78935244:A:C	S75R	0.999
4:78935244:A:T	S75R	0.999
4:78935246:T:G	S75R	0.999
4:78935253:G:C	N72K	0.999
4:78935253:G:T	N72K	0.999
4:78935263:T:A	E69V	0.999
4:78920641:A:C	H278Q	0.998
4:78920641:A:T	H278Q	0.998
4:78920646:A:G	W277R	0.998
4:78920646:A:T	W277R	0.998
4:78920657:C:A	S273I	0.998
4:78920663:C:T	G271E	0.998
4:78926562:A:G	W221R	0.998
4:78926562:A:T	W221R	0.998
4:78930182:A:C	F164L	0.998
4:78930182:A:T	F164L	0.998
4:78930184:A:G	F164L	0.998
4:78930211:A:G	C155R	0.998
4:78930213:C:T	G154D	0.998
4:78930222:C:T	G151E	0.998
4:78930223:C:G	G151R	0.998
4:78930223:C:T	G151R	0.998

dbSNP variants (sampled 300 via entrez): RS1000043750 (4:78937253 G>A,C,T), RS1000146354 (4:78919053 C>T), RS1000179194 (4:78902216 T>C), RS1000237370 (4:78897084 T>A), RS1000258969 (4:78940053 C>G,T), RS1000292252 (4:78889704 G>T), RS1000403893 (4:78904023 C>T), RS1000423895 (4:78932889 C>T), RS1000524207 (4:78927172 A>T), RS1000625713 (4:78908835 A>G), RS1000664145 (4:78890074 T>C), RS1000752947 (4:78888471 C>G,T), RS1000824702 (4:78933653 C>T), RS1000827019 (4:78908733 T>G), RS1000844070 (4:78909031 C>T)

Disease associations

OMIM: gene MIM:614577 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST003059_9	Parkinson’s disease	1.000000e-06
GCST007576_213	Chronotype	4.000000e-08
GCST90002385_251	High light scatter reticulocyte count	6.000000e-11
GCST90002386_580	High light scatter reticulocyte percentage of red cells	5.000000e-11
GCST90002387_92	Immature fraction of reticulocytes	3.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008328	chronotype measurement
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	decreases expression	2
Valproic Acid	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
bisphenol A	increases methylation	1
beta-lapachone	increases expression	1
methylparaben	increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
jinfukang	decreases expression	1
Decitabine	affects expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	affects expression	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1
Lead	affects splicing	1
Methyl Methanesulfonate	increases expression	1
Phthalic Acids	increases methylation	1
Quercetin	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Urethane	increases expression	1
Oxyquinoline	decreases expression	1

Clinical trials (associated diseases)

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