RPAP2

Summary

RPAP2 (RNA polymerase II associated protein 2, HGNC:25791) is a protein-coding gene on chromosome 1p22.1, encoding Putative RNA polymerase II subunit B1 CTD phosphatase RPAP2 (Q8IXW5). Protein phosphatase that displays CTD phosphatase activity and regulates transcription of snRNA genes. It is a selective cancer dependency (DepMap: 89.7% of cell lines).

Enables RNA polymerase II CTD heptapeptide repeat phosphatase activity. Involved in PERK-mediated unfolded protein response and snRNA transcription. Located in cilium; cytosol; and nucleolus. Part of transcription preinitiation complex.

Source: NCBI Gene 79871 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 11 total
• Cancer dependency (DepMap): dependent in 89.7% of screened cell lines
• MANE Select transcript: NM_024813

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25791
Approved symbol	RPAP2
Name	RNA polymerase II associated protein 2
Location	1p22.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ13150, Rtr1
Ensembl gene	ENSG00000122484
Ensembl biotype	protein_coding
OMIM	611476
Entrez	79871

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 9 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000477322, ENST00000484158, ENST00000610020, ENST00000885052, ENST00000915697, ENST00000915698, ENST00000957710, ENST00000957711, ENST00000957712, ENST00000957713, ENST00000957714

RefSeq mRNA: 1 — MANE Select: NM_024813 NM_024813

CCDS: CCDS740

Canonical transcript exons

ENST00000610020 — 13 exons

Exon	Start	End
ENSE00000831123	92333391	92333473
ENSE00001067523	92301476	92301590
ENSE00001144233	92323445	92324375
ENSE00001903511	92299059	92299146
ENSE00003469449	92336347	92336427
ENSE00003477461	92307188	92307276
ENSE00003490430	92303977	92304075
ENSE00003499108	92380724	92380873
ENSE00003560283	92345846	92345914
ENSE00003578690	92300194	92300239
ENSE00003654266	92320599	92320634
ENSE00003669890	92304284	92304349
ENSE00003706693	92387011	92402056

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 95.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.2094 / max 344.4867, expressed in 1799 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
4037	23.2094	1799

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	95.06	gold quality
cerebellar vermis	UBERON:0004720	91.58	gold quality
corpus callosum	UBERON:0002336	90.57	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	87.70	gold quality
adrenal tissue	UBERON:0018303	87.33	gold quality
biceps brachii	UBERON:0001507	87.20	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.06	gold quality
colonic epithelium	UBERON:0000397	86.93	gold quality
ventricular zone	UBERON:0003053	86.48	gold quality
pons	UBERON:0000988	85.37	gold quality
tonsil	UBERON:0002372	85.13	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.03	gold quality
superior vestibular nucleus	UBERON:0007227	84.99	gold quality
hindlimb stylopod muscle	UBERON:0004252	84.98	gold quality
islet of Langerhans	UBERON:0000006	84.85	gold quality
tendon	UBERON:0000043	84.81	gold quality
subthalamic nucleus	UBERON:0001906	84.66	gold quality
inferior vagus X ganglion	UBERON:0005363	84.60	gold quality
gastrocnemius	UBERON:0001388	84.04	gold quality
dorsal plus ventral thalamus	UBERON:0001897	83.88	gold quality
muscle of leg	UBERON:0001383	83.63	gold quality
ventral tegmental area	UBERON:0002691	83.60	gold quality
vena cava	UBERON:0004087	83.50	silver quality
ganglionic eminence	UBERON:0004023	83.45	gold quality
cortical plate	UBERON:0005343	83.19	gold quality
muscle organ	UBERON:0001630	83.10	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	83.08	gold quality
smooth muscle tissue	UBERON:0001135	82.95	gold quality
substantia nigra pars reticulata	UBERON:0001966	82.90	gold quality
superior surface of tongue	UBERON:0007371	82.87	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-CURD-97	yes	717.27
E-CURD-89	yes	664.43
E-MTAB-5061	yes	15.28
E-MTAB-7249	yes	10.86
E-ANND-3	yes	6.65
E-CURD-112	no	2.49

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

53 targeting RPAP2, 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-4282	99.99	75.36	6408
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-7849-3P	99.47	68.17	1224
HSA-MIR-578	99.46	68.36	1787
HSA-MIR-297	99.40	69.58	1418
HSA-MIR-302A-5P	99.39	68.21	1913
HSA-MIR-12113	99.32	67.54	1072
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-4528	99.18	69.77	1936
HSA-MIR-6799-5P	99.14	65.72	2093
HSA-MIR-6871-5P	98.90	66.67	671
HSA-MIR-487A-5P	98.85	69.37	993

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 89.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 4)

• During transcription of snRNA genes, Ser7 phosphorylation facilitates recruitment of RPAP2, which in turn both recruits Integrator and dephosphorylates Ser5. (PMID:22137580)
• These results suggest that RPAP2 controls Pol II activity through a direct interaction with Rpb6 (PMID:25639305)
• Coordination between two branches of the unfolded protein response determines apoptotic cell fate so that PERK attenuates IRE1 via RPAP2 to abort failed endoplasmic reticulum stress adaptation and trigger apoptosis. (PMID:30118681)
• Modulation of the Pol II CTD Phosphorylation Code by Rac1 and Cdc42 Small GTPases in Cultured Human Cancer Cells and Its Implication for Developing a Synthetic-Lethal Cancer Therapy. (PMID:32143485)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rpap2	ENSDARG00000038397
mus_musculus	Rpap2	ENSMUSG00000033773
rattus_norvegicus	Rpap2	ENSRNOG00000023484
drosophila_melanogaster	CG34183	FBGN0085212
caenorhabditis_elegans		WBGENE00011143

Protein

Protein identifiers

Putative RNA polymerase II subunit B1 CTD phosphatase RPAP2 — Q8IXW5 (reviewed: Q8IXW5)

Alternative names: RNA polymerase II-associated protein 2

All UniProt accessions (1): Q8IXW5

UniProt curated annotations — full annotation on UniProt →

Function. Protein phosphatase that displays CTD phosphatase activity and regulates transcription of snRNA genes. Recognizes and binds phosphorylated ‘Ser-7’ of the C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit POLR2A, and mediates dephosphorylation of ‘Ser-5’ of the CTD, thereby promoting transcription of snRNA genes. Downstream of EIF2AK3/PERK, dephosphorylates ERN1, a sensor for the endoplasmic reticulum unfolded protein response (UPR), to abort failed ER-stress adaptation and trigger apoptosis.

Subunit / interactions. Associates with the RNA polymerase II complex. Interacts with transcribing RNA polymerase II phosphorylated on ‘Ser-7’ on CTD.

Subcellular location. Cytoplasm. Nucleus.

Domain organisation. The RTR1-type zinc finger mediates interactions with RNA polymerase II complex subunits.

Similarity. Belongs to the RPAP2 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IXW5-1	1	yes
Q8IXW5-2	2

RefSeq proteins (1): NP_079089* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007308	Rtr1/RPAP2_dom	Domain
IPR038534	Rtr1/RPAP2_sf	Homologous_superfamily
IPR039693	Rtr1/RPAP2	Family

Pfam: PF04181

Catalyzed reactions (Rhea), 2 shown:

• O-phospho-L-seryl-[protein] + H2O = L-seryl-[protein] + phosphate (RHEA:20629)
• O-phospho-L-threonyl-[protein] + H2O = L-threonyl-[protein] + phosphate (RHEA:47004)

UniProt features (45 total): helix 7, mutagenesis site 6, compositionally biased region 5, modified residue 5, binding site 4, strand 4, sequence conflict 3, region of interest 3, splice variant 2, turn 2, initiator methionine 1, chain 1, zinc finger region 1, coiled-coil region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7F4G	ELECTRON MICROSCOPY	2.78
7B7U	ELECTRON MICROSCOPY	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IXW5-F1	65.05	0.16

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (4): 100; 105; 136; 140

Post-translational modifications (5): 2, 9, 216, 433, 480

Mutagenesis-validated functional residues (6):

Position	Phenotype
2–32	abolishes dephosphorylation of ern1; when associated with 275-g–e-612 del.
100	abolishes interaction with rna polymerase ii complex subunits; when associated with a-105.
105	abolishes interaction with rna polymerase ii complex subunits; when associated with a-100.
136	abolishes interaction with rna polymerase ii complex subunits; when associated with a-140.
140	abolishes interaction with rna polymerase ii complex subunits; when associated with a-136.
275–612	abolishes dephosphorylation of ern1; when associated with 2-a–l-32 del.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6807505	RNA polymerase II transcribes snRNA genes
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)

MSigDB gene sets: 108 (showing top): GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_CELLULAR_RESPONSE_TO_TOPOLOGICALLY_INCORRECT_PROTEIN, GOBP_ER_NUCLEUS_SIGNALING_PATHWAY, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, chr1p22, HOXA4_Q2, GOBP_RESPONSE_TO_TOPOLOGICALLY_INCORRECT_PROTEIN, GOCC_PROTEIN_DNA_COMPLEX, GOCC_NUCLEOLUS, GEORGES_TARGETS_OF_MIR192_AND_MIR215, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ESTER_BONDS, GOMF_PROTEIN_SERINE_THREONINE_PHOSPHATASE_ACTIVITY, GOMF_PHOSPHORIC_ESTER_HYDROLASE_ACTIVITY, GOMF_RNA_POLYMERASE_BINDING

GO Biological Process (3): snRNA transcription (GO:0009301), PERK-mediated unfolded protein response (GO:0036499), regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (8): protein serine/threonine phosphatase activity (GO:0004722), zinc ion binding (GO:0008270), RNA polymerase II CTD heptapeptide repeat phosphatase activity (GO:0008420), RNA polymerase core enzyme binding (GO:0043175), phosphoprotein phosphatase activity (GO:0004721), protein binding (GO:0005515), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), cilium (GO:0005929), transcription preinitiation complex (GO:0097550)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
RNA Polymerase II Transcription	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
nuclear lumen	2
DNA-templated transcription	1
snRNA metabolic process	1
ER-nucleus signaling pathway	1
endoplasmic reticulum unfolded protein response	1
integrated stress response signaling	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
phosphoprotein phosphatase activity	1
transition metal ion binding	1
protein serine/threonine phosphatase activity	1
RNA polymerase II CTD heptapeptide repeat modifying activity	1
RNA polymerase binding	1
phosphatase activity	1
catalytic activity, acting on a protein	1
binding	1
catalytic activity	1
cation binding	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
cytoplasm	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
protein-DNA complex	1

Protein interactions and networks

STRING

994 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPAP2	GPN1	Q9HCN4	967
RPAP2	RPAP1	Q9BWH6	932
RPAP2	RPAP3	Q9H6T3	913
RPAP2	RPRD1A	Q96P16	897
RPAP2	CTDP1	Q9Y5B0	866
RPAP2	POLR2J	P52435	837
RPAP2	PFDN6	O15212	833
RPAP2	INTS3	Q68E01	813
RPAP2	SSU72	Q9NP77	810
RPAP2	RUVBL1	P82276	808
RPAP2	RPRD1B	Q9NQG5	808
RPAP2	RUVBL2	Q9Y230	780
RPAP2	RPRD2	Q5VT52	777
RPAP2	MED17	Q9NVC6	770
RPAP2	RTF1	Q92541	746

IntAct

123 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
MED21	MED19	psi-mi:“MI:0914”(association)	0.880
POLR2E	POLR3A	psi-mi:“MI:0914”(association)	0.870
RPAP2	GPN1	psi-mi:“MI:0915”(physical association)	0.840
MED31	MED19	psi-mi:“MI:0914”(association)	0.840
MED7	MED19	psi-mi:“MI:0914”(association)	0.840
MED18	MED19	psi-mi:“MI:0914”(association)	0.840
POLR2G	POLR2D	psi-mi:“MI:0914”(association)	0.840
POLR2J	POLR1C	psi-mi:“MI:0914”(association)	0.830
RPAP2	RPRD1B	psi-mi:“MI:0407”(direct interaction)	0.810
RPRD1B	RPAP2	psi-mi:“MI:0915”(physical association)	0.810
RPAP2	PIH1D1	psi-mi:“MI:0915”(physical association)	0.800
MED30	MED19	psi-mi:“MI:0914”(association)	0.790
PPP1CC	CCDC85C	psi-mi:“MI:0914”(association)	0.740
POLR2D	MED19	psi-mi:“MI:0914”(association)	0.730
POLR2E	MED19	psi-mi:“MI:0914”(association)	0.730
RPRD1B	POLR2D	psi-mi:“MI:0914”(association)	0.730
MED19	MED19	psi-mi:“MI:0914”(association)	0.730
MED26	MED19	psi-mi:“MI:0914”(association)	0.730
POLR2A	POLR2D	psi-mi:“MI:0914”(association)	0.730
POLR2D	POLR2C	psi-mi:“MI:0914”(association)	0.730
MED28	MED19	psi-mi:“MI:0914”(association)	0.730
MED1	MED14	psi-mi:“MI:0914”(association)	0.730
RPRD1B	RECQL5	psi-mi:“MI:0914”(association)	0.730
POLR2G	RECQL5	psi-mi:“MI:0914”(association)	0.730
POLR2J	POLR2D	psi-mi:“MI:0914”(association)	0.730

BioGRID (278): RPAP2 (Affinity Capture-MS), RPAP2 (Affinity Capture-MS), RPAP2 (Affinity Capture-MS), RPAP2 (Affinity Capture-MS), RPAP2 (Affinity Capture-MS), RPAP2 (Affinity Capture-MS), RPAP2 (Affinity Capture-MS), RPAP2 (Affinity Capture-MS), RPAP2 (Proximity Label-MS), RPAP2 (Proximity Label-MS), RPAP2 (Proximity Label-MS), RPAP2 (Proximity Label-MS), RPAP2 (Proximity Label-MS), RPAP2 (Affinity Capture-MS), RPAP2 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8ENT6, A2BGP7, A2CJ06, B1H1W9, F6RRD7, O00124, O55036, P54274, Q1LV50, Q1LWH4, Q1T7B8, Q28HU3, Q3KNJ2, Q3U1D0, Q3US16, Q4KLN8, Q4V832, Q5I0E6, Q5I2W8, Q5NVA9, Q5RA37, Q5RET9, Q5XI46, Q5ZIN2, Q6AYI4, Q6DRL4, Q6IQ49, Q6IRN0, Q6NV18, Q6P1H6, Q7Z2Z1, Q7Z4M0, Q8BJW7, Q8BKT3, Q8BMG1, Q8BMI4, Q8BQ33, Q8IXW5, Q8K1J5, Q8VC34

Diamond homologs: A2Y040, A8DYY5, B0UYH6, F4K1B1, F6RRD7, Q5I0E6, Q5RA37, Q6AVZ9, Q8IXW5, Q8VC34, O42853, P30641, P40084, Q12378

SIGNOR signaling

24 interactions.

A	Effect	B	Mechanism
RPAP2	“up-regulates activity”	POLR2A	dephosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 95 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
FGFR2 mutant receptor activation	11	121.4×	2e-20
Signaling by FGFR2 IIIa TM	12	104.5×	8e-21
Abortive elongation of HIV-1 transcript in the absence of Tat	13	93.5×	2e-21
MicroRNA (miRNA) biogenesis	12	79.4×	1e-19
RNA Pol II CTD phosphorylation and interaction with CE during HIV infection	13	76.8×	1e-20
RNA Pol II CTD phosphorylation and interaction with CE	13	76.8×	1e-20
Signaling by FGFR in disease	12	73.6×	3e-19
FGFR2 alternative splicing	12	73.6×	3e-19

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of transcription elongation by RNA polymerase II	13	42.5×	1e-15
RNA polymerase II preinitiation complex assembly	12	35.5×	1e-13
positive regulation of transcription initiation by RNA polymerase II	12	35.5×	1e-13
transcription initiation at RNA polymerase II promoter	6	24.4×	2e-05
somatic stem cell population maintenance	6	16.2×	1e-04
transcription by RNA polymerase II	15	11.5×	4e-10
protein stabilization	9	6.5×	6e-04
protein ubiquitination	11	5.0×	8e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	6
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2401 predictions. Top by Δscore:

Variant	Effect	Δscore
1:92299142:CGCAG:C	donor_loss	1.0000
1:92299144:CAGG:C	donor_loss	1.0000
1:92299145:AGG:A	donor_loss	1.0000
1:92301470:TTTTA:T	acceptor_loss	1.0000
1:92301472:TTAG:T	acceptor_loss	1.0000
1:92301473:TAGGA:T	acceptor_loss	1.0000
1:92301474:A:AG	acceptor_gain	1.0000
1:92301474:AG:A	acceptor_gain	1.0000
1:92301475:G:GT	acceptor_gain	1.0000
1:92301475:G:T	acceptor_loss	1.0000
1:92301475:GG:G	acceptor_gain	1.0000
1:92301475:GGA:G	acceptor_gain	1.0000
1:92301475:GGAA:G	acceptor_gain	1.0000
1:92301475:GGAAA:G	acceptor_gain	1.0000
1:92301584:G:GT	donor_gain	1.0000
1:92301586:A:T	donor_gain	1.0000
1:92301587:G:GG	donor_gain	1.0000
1:92301589:GT:G	donor_gain	1.0000
1:92301591:G:GG	donor_gain	1.0000
1:92301595:GTGT:G	donor_gain	1.0000
1:92301596:TGTT:T	donor_gain	1.0000
1:92301598:T:G	donor_gain	1.0000
1:92301598:T:TG	donor_gain	1.0000
1:92303486:GAA:G	donor_gain	1.0000
1:92303973:TTA:T	acceptor_loss	1.0000
1:92303975:A:AG	acceptor_gain	1.0000
1:92303975:A:AT	acceptor_loss	1.0000
1:92303975:AG:A	acceptor_gain	1.0000
1:92303975:AGG:A	acceptor_gain	1.0000
1:92303976:G:GA	acceptor_loss	1.0000

AlphaMissense

4043 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:92324049:T:A	W377R	0.997
1:92324049:T:C	W377R	0.997
1:92307191:T:C	F135L	0.996
1:92307193:T:A	F135L	0.996
1:92307193:T:G	F135L	0.996
1:92345883:T:A	W553R	0.995
1:92345883:T:C	W553R	0.995
1:92304023:G:C	R94P	0.993
1:92307257:T:A	W157R	0.993
1:92307257:T:C	W157R	0.993
1:92304022:C:A	R94S	0.991
1:92301550:T:C	L65P	0.990
1:92304327:T:A	V126D	0.990
1:92304040:T:C	C100R	0.989
1:92307206:T:C	C140R	0.989
1:92304299:T:G	Y117D	0.988
1:92304300:A:C	Y117S	0.988
1:92304306:T:C	I119T	0.988
1:92307215:G:C	A143P	0.988
1:92307218:T:C	S144P	0.988
1:92324051:G:C	W377C	0.987
1:92324051:G:T	W377C	0.987
1:92304040:T:A	C100S	0.986
1:92304041:G:C	C100S	0.986
1:92307206:T:A	C140S	0.986
1:92307207:G:C	C140S	0.986
1:92304001:T:G	Y87D	0.985
1:92304306:T:G	I119S	0.985
1:92307208:T:G	C140W	0.985
1:92336412:T:C	L535P	0.985

dbSNP variants (sampled 300 via entrez): RS1000073331 (1:92342408 G>A), RS1000077876 (1:92310826 G>A), RS1000123636 (1:92391308 G>A,T), RS1000143339 (1:92362129 A>G), RS1000187867 (1:92350839 G>A), RS1000198436 (1:92354501 A>C), RS1000201577 (1:92397356 C>T), RS1000233490 (1:92334223 A>G), RS1000265197 (1:92301132 G>A), RS1000272061 (1:92354977 C>G,T), RS1000275242 (1:92397712 A>C), RS1000307406 (1:92318754 C>A), RS1000324944 (1:92350452 T>C), RS1000385183 (1:92339208 T>G), RS1000412883 (1:92396961 C>T)

Disease associations

OMIM: gene MIM:611476 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST004608_9	Granulocyte percentage of myeloid white cells	3.000000e-34
GCST004625_7	Monocyte count	1.000000e-20
GCST004633_135	Neutrophil percentage of white cells	2.000000e-11
GCST007121_1	Multiple sclerosis and C-reactive protein levels (pleiotropy)	9.000000e-08
GCST90002388_608	Lymphocyte count	7.000000e-10
GCST90002399_43	Neutrophil percentage of white cells	1.000000e-16
GCST90013445_13	Type 1 diabetes	1.000000e-08
GCST90013445_27	Type 1 diabetes	1.000000e-08

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0005091	monocyte count
EFO:0007990	neutrophil percentage of leukocytes
EFO:0004458	C-reactive protein measurement
EFO:0004587	lymphocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	3
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression	1
beta-methylcholine	affects expression	1
2-palmitoylglycerol	increases expression	1
abrine	increases expression	1
jinfukang	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Air Pollutants	increases abundance, decreases expression	1
Atrazine	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Smoke	decreases expression, increases abundance	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tunicamycin	increases expression	1
Aflatoxin M1	decreases expression	1
Cadmium Chloride	decreases expression	1
Lactic Acid	decreases expression	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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