PLEKHO1

Summary

PLEKHO1 (pleckstrin homology domain containing O1, HGNC:24310) is a protein-coding gene on chromosome 1q21.2, encoding Pleckstrin homology domain-containing family O member 1 (Q53GL0). Plays a role in the regulation of the actin cytoskeleton through its interactions with actin capping protein (CP).

Predicted to be involved in regulation of myoblast fusion. Predicted to act upstream of or within several processes, including lamellipodium morphogenesis; myoblast fusion; and myoblast migration. Predicted to be located in cytoplasm; nucleus; and plasma membrane. Predicted to be active in muscle cell projection membrane and ruffle membrane.

Source: NCBI Gene 51177 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 77 total
• MANE Select transcript: NM_016274

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24310
Approved symbol	PLEKHO1
Name	pleckstrin homology domain containing O1
Location	1q21.2
Locus type	gene with protein product
Status	Approved
Aliases	CKIP-1, OC120
Ensembl gene	ENSG00000023902
Ensembl biotype	protein_coding
OMIM	608335
Entrez	51177

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 4 protein_coding_CDS_not_defined, 3 retained_intron, 2 protein_coding

ENST00000369124, ENST00000369126, ENST00000441340, ENST00000477309, ENST00000479194, ENST00000485470, ENST00000492304, ENST00000502767, ENST00000607609

RefSeq mRNA: 4 — MANE Select: NM_016274 NM_001304722, NM_001304723, NM_001304724, NM_016274

CCDS: CCDS76210, CCDS945

Canonical transcript exons

ENST00000369124 — 6 exons

Exon	Start	End
ENSE00001844604	150158819	150160065
ENSE00001915712	150149916	150150287
ENSE00003493678	150156911	150157015
ENSE00003534043	150156066	150156206
ENSE00003605784	150157385	150157486
ENSE00003616995	150150912	150151058

Expression profiles

Bgee: expression breadth ubiquitous, 243 present calls, max score 98.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.1100 / max 470.7026, expressed in 1731 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5056	14.7142	1662
5058	9.2365	1551
5057	1.4389	679
5055	1.0253	600
201720	0.3115	152
5053	0.1636	70
5054	0.1226	53
5059	0.0535	11
5060	0.0438	24

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus muscularis layer	UBERON:0035833	98.99	gold quality
lower esophagus	UBERON:0013473	98.97	gold quality
monocyte	CL:0000576	98.80	gold quality
mononuclear cell	CL:0000842	98.75	gold quality
leukocyte	CL:0000738	98.70	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.69	gold quality
mucosa of stomach	UBERON:0001199	98.64	gold quality
granulocyte	CL:0000094	98.60	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.58	gold quality
left testis	UBERON:0004533	98.31	gold quality
right testis	UBERON:0004534	98.28	gold quality
popliteal artery	UBERON:0002250	98.23	gold quality
tibial artery	UBERON:0007610	98.23	gold quality
right coronary artery	UBERON:0001625	97.54	gold quality
aorta	UBERON:0000947	97.53	gold quality
ganglionic eminence	UBERON:0004023	97.23	gold quality
left uterine tube	UBERON:0001303	97.17	gold quality
left coronary artery	UBERON:0001626	96.99	gold quality
thoracic aorta	UBERON:0001515	96.73	gold quality
apex of heart	UBERON:0002098	96.73	gold quality
ascending aorta	UBERON:0001496	96.72	gold quality
cortical plate	UBERON:0005343	96.66	gold quality
coronary artery	UBERON:0001621	96.54	gold quality
descending thoracic aorta	UBERON:0002345	96.35	gold quality
spleen	UBERON:0002106	96.17	gold quality
gall bladder	UBERON:0002110	96.09	gold quality
vermiform appendix	UBERON:0001154	96.02	gold quality
body of uterus	UBERON:0009853	96.02	gold quality
testis	UBERON:0000473	95.99	gold quality
ventricular zone	UBERON:0003053	95.81	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-9221	yes	16.77
E-CURD-88	yes	7.87
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GLI2, JUN, TAL1

miRNA regulators (miRDB)

37 targeting PLEKHO1, 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-7110-3P	100.00	73.18	2486
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4500	99.99	72.72	2367
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-12130	99.75	65.47	452
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-4688	99.48	64.68	828
HSA-MIR-6743-5P	99.48	63.60	721
HSA-MIR-3911	99.38	66.95	1087
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-3978	99.24	68.39	2201

Literature-anchored findings (GeneRIF, showing 30)

• examination of CK2alpha for a region that mediates interactions with CKIP-1 revealed a putative HIKE domain; this motif by itself may not be sufficient to mediate interactions. (PMID:15254037)
• CKIP-1 is cleaved by caspase-3 during apoptosis. C-terminal fragments translocate to the cytoplasm and nucleus and inhibit AP-1 activity via direct interaction with c-Jun and JunD. CKIP-1 also forms a feedback with caspase-3 and enhances apoptosis. (PMID:15706351)
• CKIP-1 plays a role in the regulation of the actin cytoskeleton through its interactions with actin capping protein. (PMID:15831458)
• CKIP-1 could interact with ATM and recruits nuclear ATM proteins partially to the plasma membrane. The results provide the first evidence that ATM, a predominantly nuclear kinase, could be re-localized to the plasma membrane. (PMID:16325375)
• Data provide evidence that ATM, a predominantly nuclear kinase, could be relocalized to the plasma membrane by CKIP-1. (PMID:16325375)
• CKIP-1 has a role in cell morphology that depends on its interaction with actin-capping protein (PMID:16987810)
• The results provide a novel role of CKIP-1 in cytokine signaling response and the biochemical mechanism, by which two previously identified modulators IFP35 and Nmi are involved via interactions. (PMID:17197158)
• Results indicate that CKIP-1, a novel Akt PH domain-interacting protein, would be a candidate of tumor suppressor with an Akt inhibitory function. (PMID:17942896)
• The N-terminal PH domain and C-terminal auto-inhibitory region of CKIP-1 coordinate to determine its subcellular localization and the nucleus-plasma membrane shuttling. (PMID:20171213)
• CKIP-1 is involved in various important signaling pathways, controlling cell growth, apoptosis, differentiation, cytoskeleton and bone formation–REVIEW (PMID:22878216)
• CKIP-1, through its leucine zipper, interacts with the Rpt6 and mediates the Smurf1-Rpt6 interaction. (PMID:23032291)
• overexpression triggers classical monocyte activation and transactivation of the TNF promoter (PMID:23583459)
• CKIP-1 controlled Smurf1 expression in colon cancer (PMID:23995790)
• CKIP-1 interacts with CARMA1 and has an inhibitory effect on PKCtheta;-CBM-NF-kappaB signaling. (PMID:24465689)
• High expression levels of CKIP1 were associated with the development of lung cancer, and that CKIP1 knockdown may block tumor cell growth mainly by promoting cell apoptosis. (PMID:25966172)
• There is a major role of the CK2alpha-interacting protein CKIP-1 in activation of PAK1 for neoplastic prostate cells transformation. (PMID:26160174)
• New light on the molecular mechanism of cell adhesion-mediated drug resistance in Non-Hodgkin’s Lymphoma (NHL) and targeting CKIP-1 may be a novel therapeutic target for NHL. (PMID:27840970)
• the increased PLEKHO1 could suppress Smad-dependent BMP signaling to inhibit bone formation during aging. (PMID:28083909)
• these data integrated CKIP-1 expression and function as a novel transcriptional regulator of macrophage polarization. (PMID:28212865)
• we firstly revealed the association of CKIP-1 rs2306235 polymorphism with an increased risk of CHF in Chinese Han populations. (PMID:28402261)
• we provided the first line of evidence that CKIP-1 regulated megakaryocytic differentiation and CKIP-1 knockout mice showed defective megakaryopoiesis and platelet production, suggesting a novel role for CKIP-1 in hematopoietic differentiation. (PMID:28404913)
• CKIP-1 could interact with Neuropilin-1 (NRP1). (PMID:29852799)
• The molecular functions of CKIP-1 in cell morphology, cell differentiation and cell apoptosis, the involved biological processes including bone formation, tumorigenesis and immune regulation are REVIEWED. The potential role of CKIP-1 in the treatment of human diseases such as osteoporosis, tumor, and atherosclerosis is indicated. (PMID:31082489)
• The results showed that PLEKHO1 knockdown significantly inhibited cell viability and facilitated apoptosis in vitro and impaired tumour formation in vivo. (PMID:31180521)
• mechanistic investigations suggested that CKIP-1 sharply suppressed the activity of AKT by inhibiting the phosphorylation, markedly downregulated the phosphorylated GSK3beta at Ser9, and promoted beta-catenin degradation. (PMID:31355268)
• High expression of the CKIP-1 gene might promote apoptosis through downregulation of the Ras/ERK signalling pathway in the intestinal type of gastric cancer. (PMID:32223671)
• [Effect of CKIP-1 on hepatocyte apoptosis in nonalcoholic fatty liver disease]. (PMID:36631036)
• CKIP-1 Promotes P. gingivalis-Induced Inflammation of Periodontal Soft Tissues by Inhibiting Autophagy. (PMID:37351817)
• Associations of CKIP-1 and LOX-1 polymorphisms with the risk of type 2 diabetes mellitus with hypertension among Chinese adults. (PMID:37668684)
• CKIP-1 silencing suppresses OSCC via mitochondrial homeostasis-associated TFAM/cGAS-STING signalling axis. (PMID:39169452)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	plekho1a	ENSDARG00000061191
danio_rerio	plekho1b	ENSDARG00000077499
mus_musculus	Plekho1	ENSMUSG00000015745
rattus_norvegicus	Plekho1	ENSRNOG00000021170

Paralogs (1): PLEKHO2 (ENSG00000241839)

Protein

Protein identifiers

Pleckstrin homology domain-containing family O member 1 — Q53GL0 (reviewed: Q53GL0)

Alternative names: C-Jun-binding protein, Casein kinase 2-interacting protein 1, Osteoclast maturation-associated gene 120 protein

All UniProt accessions (2): Q53GL0, Q5T4P9

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the regulation of the actin cytoskeleton through its interactions with actin capping protein (CP). May function to target CK2 to the plasma membrane thereby serving as an adapter to facilitate the phosphorylation of CP by protein kinase 2 (CK2). Appears to target ATM to the plasma membrane. Appears to also inhibit tumor cell growth by inhibiting AKT-mediated cell-survival. Also implicated in PI3K-regulated muscle differentiation, the regulation of AP-1 activity (plasma membrane bound AP-1 regulator that translocates to the nucleus) and the promotion of apoptosis induced by tumor necrosis factor TNF. When bound to PKB, it inhibits it probably by decreasing PKB level of phosphorylation.

Subunit / interactions. Heterodimer or homodimer. Interacts with CK2 and actin capping subunits (capping protein CP-alpha and CP-beta). CKIP1 and CK2 together inhibit the activity of actin capping protein at the barbed ends of actin filaments. Interacts with ATM, IFP35, JUN, JUND, NMI and PI3K. Interacts with AKT1, AKT2 and AKT3 (each isozyme of PKB), PtdIns(3,5)P2, PtdIns(4,5)P2 and PtdIns(3,4,5)P2.

Subcellular location. Cell membrane. Nucleus. Cytoplasm.

Tissue specificity. Abundantly expressed in skeletal muscle and heart, moderately in kidney, liver, brain and placenta and sparingly in the pancreas and lung. Easily detectable in cell lines such as MOLT-4, HEK293 and Jurkat.

Post-translational modifications. C-terminal fragments could be released during apoptosis via caspase-3-dependent cleavage.

Induction. Up-regulated by IFNG/IFN-gamma and IL2/interleukin-2 or in C2C12 cells.

Isoforms (2)

UniProt ID	Names	Canonical?
Q53GL0-1	1	yes
Q53GL0-2	2

RefSeq proteins (4): NP_001291651, NP_001291652, NP_001291653, NP_057358* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001849	PH_domain	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR043448	PKHO1/2	Family

Pfam: PF00169

UniProt features (36 total): mutagenesis site 13, region of interest 7, site 4, modified residue 3, compositionally biased region 2, sequence conflict 2, chain 1, domain 1, splice variant 1, sequence variant 1, helix 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3AA1	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q53GL0-F1	69.33	0.33

Functional residue map

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

Catalytic / active sites (4): 155 (interacts with capping protein); 157 (interacts with capping protein); 310–311 (cleavage; by caspase-3); 345–346 (cleavage; by caspase-3)

Post-translational modifications (3): 227, 271, 342

Mutagenesis-validated functional residues (13):

Position	Phenotype
42	no effect on subcellular localization. no effect on subcellular localization; when associated with c-44. disruption of m
44	no effect on subcellular localization. no effect on subcellular localization; when associated with c-42. disruption of m
123	disruption of membrane localization and impaired interaction with ck2. loss of phospholipid binding; when associated wit
133	no effect on binding to capping proteins and loss of phospholipid binding; when associated with a-135 and a-137.
133	no effect on binding to capping proteins; when associated with e-135.
135	no effect on binding to capping proteins; when associated with a-133 and a-137.
135	no effect on binding to capping proteins; when associated with e-133.
137	no effect on binding to capping proteins; when associated with a-133 and a-135.
155	no change in cell morphology and actin cytoskeleton. great loss of binding to capping proteins; when associated with a-1
155	no change in cell morphology and actin cytoskeleton. great loss of binding to capping proteins and no change in cell mor
157	no change in cell morphology and actin cytoskeleton. great loss of binding to capping proteins; when associated with a-1
157	no change in cell morphology and actin cytoskeleton. great loss of binding to capping proteins and no change in cell mor
159	great loss of binding to capping proteins; when associated with a-155 and a-157.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 257 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOCC_RUFFLE, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, LE_EGR2_TARGETS_UP, CASTELLANO_NRAS_TARGETS_DN, GOBP_REGULATION_OF_SYNCYTIUM_FORMATION_BY_PLASMA_MEMBRANE_FUSION, SANSOM_APC_TARGETS_DN, GOBP_LAMELLIPODIUM_ORGANIZATION, GOBP_MYOTUBE_DIFFERENTIATION, MULLIGHAN_NPM1_SIGNATURE_3_DN, GOBP_CELL_PROJECTION_ORGANIZATION, KIM_WT1_TARGETS_12HR_UP

GO Biological Process (5): myoblast fusion (GO:0007520), regulation of cell shape (GO:0008360), myoblast migration (GO:0051451), lamellipodium morphogenesis (GO:0072673), regulation of myoblast fusion (GO:1901739)

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

GO Cellular Component (6): nucleus (GO:0005634), cytoplasm (GO:0005737), ruffle membrane (GO:0032587), muscle cell projection membrane (GO:0036195), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cell projection membrane	2
syncytium formation by cell-cell fusion	1
myotube differentiation	1
regulation of cell morphogenesis	1
regulation of biological quality	1
muscle cell migration	1
lamellipodium organization	1
plasma membrane bounded cell projection morphogenesis	1
myoblast fusion	1
regulation of syncytium formation by plasma membrane fusion	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
ruffle	1
leading edge membrane	1
muscle cell projection	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

380 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLEKHO1	CSNK2A2	P19784	981
PLEKHO1	N0E472	N0E472	718
PLEKHO1	SMURF1	Q9HCE7	690
PLEKHO1	CSNK2B	P07312	682
PLEKHO1	JUN	P05412	641
PLEKHO1	PLEK2	Q9NYT0	616
PLEKHO1	PLEK	P08567	614
PLEKHO1	IFI35	P80217	606
PLEKHO1	CARMIL1	Q5VZK9	593
PLEKHO1	NMI	Q13287	588
PLEKHO1	AKT1	P31749	504
PLEKHO1	CD2AP	Q9Y5K6	474
PLEKHO1	ATM	Q13315	463
PLEKHO1	RCSD1	Q6JBY9	395
PLEKHO1	DUXA	A6NLW8	370

IntAct

109 interactions, top by confidence:

A	B	Type	Score
ODAD1	HGS	psi-mi:“MI:0914”(association)	0.850
PSMC5	PLEKHO1	psi-mi:“MI:0915”(physical association)	0.660
PLEKHO1	PSMC5	psi-mi:“MI:0407”(direct interaction)	0.660
PSMC5	PLEKHO1	psi-mi:“MI:0407”(direct interaction)	0.660
PLEKHO1	PSMC5	psi-mi:“MI:0915”(physical association)	0.660
PLEKHO1	PSMC5	psi-mi:“MI:0403”(colocalization)	0.660
PLEKHO1	PSMC5	psi-mi:“MI:0914”(association)	0.660
CAPZB	CNOT1	psi-mi:“MI:0914”(association)	0.640
CAPZA2	CNOT1	psi-mi:“MI:0914”(association)	0.640
DDAH2	EPB41L2	psi-mi:“MI:0914”(association)	0.640
SMURF1	PLEKHO1	psi-mi:“MI:0915”(physical association)	0.640
PLEKHO1	SMURF1	psi-mi:“MI:0915”(physical association)	0.640
SMURF1	PLEKHO1	psi-mi:“MI:0407”(direct interaction)	0.620
ARLN	PLEKHO1	psi-mi:“MI:0915”(physical association)	0.560
BNIP2	PLEKHO1	psi-mi:“MI:0915”(physical association)	0.560
CYP4F2	PLEKHO1	psi-mi:“MI:0915”(physical association)	0.560
PLEKHO1	TSPO2	psi-mi:“MI:0915”(physical association)	0.560
VAMP3	PLEKHO1	psi-mi:“MI:0915”(physical association)	0.560
MMD	PLEKHO1	psi-mi:“MI:0915”(physical association)	0.560
PLEKHO1	LRP10	psi-mi:“MI:0915”(physical association)	0.560
ADAM33	PLEKHO1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (130): AKT1 (Reconstituted Complex), AKT2 (Reconstituted Complex), PLEKHO1 (Affinity Capture-Western), PLEKHO1 (Affinity Capture-Western), PLEKHO1 (Affinity Capture-Western), PLEKHO1 (Affinity Capture-Western), PLEKHO1 (Affinity Capture-Western), PLEKHO1 (Affinity Capture-MS), PLEKHO1 (Affinity Capture-MS), SEC24D (Affinity Capture-MS), CENPV (Affinity Capture-MS), CAPZA1 (Affinity Capture-MS), CAPZB (Affinity Capture-MS), RPL26L1 (Affinity Capture-MS), PDCD11 (Affinity Capture-MS)

ESM2 similar proteins: A0JN71, A4IFK0, A5PMU4, A6QQV9, O15034, O15040, O62666, O62674, O62675, O62676, O62677, O62678, O75995, P49796, P52734, P59672, P78314, P97432, P98174, Q06649, Q0V8R5, Q13905, Q14596, Q3U0J8, Q501R9, Q53GL0, Q5BJM5, Q5F3C8, Q5RC94, Q5SUE8, Q6AI12, Q6ZMT1, Q7Z5H3, Q80U40, Q80UZ0, Q80XA6, Q80YS6, Q8BL80, Q8K352, Q8N556

Diamond homologs: A4IFK0, A4IG55, Q32LQ1, Q53GL0, Q5BJM5, Q5F3C8, Q8K124, Q8TD55, Q9JIY0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	65
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

876 predictions. Top by Δscore:

Variant	Effect	Δscore
1:150150284:GCGG:G	donor_gain	1.0000
1:150151055:GGAG:G	donor_gain	1.0000
1:150151056:G:GT	donor_gain	1.0000
1:150151059:GTG:G	donor_loss	1.0000
1:150151060:T:A	donor_loss	1.0000
1:150156061:CCTA:C	acceptor_loss	1.0000
1:150156062:CTAGG:C	acceptor_loss	1.0000
1:150156063:TAGGT:T	acceptor_loss	1.0000
1:150156064:A:AT	acceptor_loss	1.0000
1:150156167:C:T	donor_gain	1.0000
1:150156203:CACGG:C	donor_loss	1.0000
1:150156205:CGGTA:C	donor_loss	1.0000
1:150156207:G:GG	donor_gain	1.0000
1:150156208:T:A	donor_loss	1.0000
1:150156909:A:AG	acceptor_gain	1.0000
1:150156910:G:A	acceptor_loss	1.0000
1:150156910:G:GG	acceptor_gain	1.0000
1:150156997:GAACC:G	donor_gain	1.0000
1:150157011:A:G	donor_gain	1.0000
1:150157014:AGG:A	donor_loss	1.0000
1:150157015:GG:G	donor_loss	1.0000
1:150158815:ACAG:A	acceptor_gain	1.0000
1:150158816:C:G	acceptor_gain	1.0000
1:150158816:CAGGC:C	acceptor_loss	1.0000
1:150158817:A:AG	acceptor_gain	1.0000
1:150158817:A:C	acceptor_loss	1.0000
1:150158817:AG:A	acceptor_gain	1.0000
1:150158818:G:GA	acceptor_gain	1.0000
1:150158818:GG:G	acceptor_gain	1.0000
1:150158818:GGC:G	acceptor_gain	1.0000

AlphaMissense

2652 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:150156959:T:A	W123R	1.000
1:150156959:T:C	W123R	1.000
1:150157454:C:A	R165S	1.000
1:150157461:C:A	P167Q	1.000
1:150150957:G:C	G26R	0.999
1:150151002:T:A	W41R	0.999
1:150151002:T:C	W41R	0.999
1:150156172:T:C	F95S	0.999
1:150157416:A:G	H152R	0.999
1:150157417:T:A	H152Q	0.999
1:150157417:T:G	H152Q	0.999
1:150157432:G:C	R157S	0.999
1:150157432:G:T	R157S	0.999
1:150157451:C:A	R164S	0.999
1:150157460:C:A	P167T	0.999
1:150157460:C:T	P167S	0.999
1:150157467:G:C	R169T	0.999
1:150157467:G:T	R169M	0.999
1:150157468:G:C	R169S	0.999
1:150157468:G:T	R169S	0.999
1:150157472:C:G	H171D	0.999
1:150157473:A:G	H171R	0.999
1:150157474:C:A	H171Q	0.999
1:150157474:C:G	H171Q	0.999
1:150157476:T:C	L172P	0.999
1:150150958:G:A	G26D	0.998
1:150150960:T:A	W27R	0.998
1:150150960:T:C	W27R	0.998
1:150151039:T:C	L53P	0.998
1:150156155:G:C	K89N	0.998

dbSNP variants (sampled 300 via entrez): RS1000077007 (1:150153758 G>A), RS1000281247 (1:150153491 G>A,T), RS1000892977 (1:150152390 C>T), RS1000946285 (1:150158494 T>C), RS1001491082 (1:150152703 A>C,G), RS1001795063 (1:150153231 A>G), RS1002212861 (1:150157827 A>G), RS1002396435 (1:150152015 G>A), RS1002494101 (1:150158159 A>G), RS1003400852 (1:150150706 T>G), RS1003594602 (1:150150831 A>C), RS1004538719 (1:150147973 G>A), RS1004875671 (1:150153203 T>C), RS1004882034 (1:150153012 C>G,T), RS1005930223 (1:150151596 C>T)

Disease associations

OMIM: gene MIM:608335 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002539_32	Schizophrenia	4.000000e-10
GCST006803_67	Schizophrenia	7.000000e-10
GCST008103_32	Bipolar disorder	5.000000e-08
GCST010002_366	Refractive error	3.000000e-15

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, increases expression	5
bisphenol A	decreases methylation, increases expression	2
sodium arsenite	increases abundance, decreases expression, affects cotreatment	2
Arsenic Trioxide	increases response to substance, decreases expression	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
Nickel	increases expression	2
Cyclosporine	increases expression	2
Aflatoxin B1	decreases methylation, increases expression	2
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
lead acetate	increases expression	1
zinc chromate	decreases expression, increases abundance	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	decreases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
bisphenol S	affects cotreatment, increases methylation	1
(+)-JQ1 compound	decreases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Atrazine	decreases expression	1
Cisplatin	decreases expression	1
Diuron	decreases expression	1
Doxorubicin	increases expression	1
Fluorouracil	affects response to substance	1
Hydrogen Peroxide	affects expression	1

Clinical trials (associated diseases)

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