PRAG1

Summary

PRAG1 (PEAK1 related, kinase-activating pseudokinase 1, HGNC:25438) is a protein-coding gene on chromosome 8p23.1, encoding Inactive tyrosine-protein kinase PRAG1 (Q86YV5). Catalytically inactive protein kinase that acts as a scaffold protein.

This gene encodes an enzyme that belongs to the tyrosine protein kinase family. A similar protein in rat binds to Rho family GTPase 2 (Rnd2) and regulates neurite outgrowth via activation of Ras homolog gene family, member A (RhoA).

Source: NCBI Gene 157285 — RefSeq curated summary.

At a glance

• GWAS associations: 69
• Clinical variants (ClinVar): 423 total — 1 pathogenic
• MANE Select transcript: NM_001080826

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25438
Approved symbol	PRAG1
Name	PEAK1 related, kinase-activating pseudokinase 1
Location	8p23.1
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp761P0423, SgK223, PRAGMIN, PEAK2, NACK
Ensembl gene	ENSG00000275342
Ensembl biotype	protein_coding
OMIM	617344
Entrez	157285

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000615670, ENST00000933693

RefSeq mRNA: 2 — MANE Select: NM_001080826 NM_001080826, NM_001369759

CCDS: CCDS43706

Canonical transcript exons

ENST00000615670 — 6 exons

Exon	Start	End
ENSE00003713707	8376247	8378078
ENSE00003717641	8381418	8381834
ENSE00003727976	8386321	8386439
ENSE00003748037	8327710	8328461
ENSE00003750577	8339478	8339635
ENSE00003751202	8317736	8319302

Expression profiles

Bgee: expression breadth ubiquitous, 243 present calls, max score 99.17.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.2950 / max 342.5205, expressed in 1571 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
91739	11.2133	1551
91738	0.5506	321
91740	0.4130	231
91742	0.0504	13
91741	0.0424	12
205062	0.0253	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar vermis	UBERON:0004720	99.17	gold quality
pancreatic ductal cell	CL:0002079	98.05	gold quality
ileal mucosa	UBERON:0000331	96.93	gold quality
middle temporal gyrus	UBERON:0002771	95.41	gold quality
gingival epithelium	UBERON:0001949	94.04	silver quality
buccal mucosa cell	CL:0002336	93.91	gold quality
epithelial cell of pancreas	CL:0000083	93.85	silver quality
Brodmann (1909) area 23	UBERON:0013554	93.85	gold quality
ventricular zone	UBERON:0003053	93.42	gold quality
jejunal mucosa	UBERON:0000399	93.40	gold quality
gingiva	UBERON:0001828	93.07	gold quality
amniotic fluid	UBERON:0000173	92.13	gold quality
cerebellum	UBERON:0002037	90.86	gold quality
epithelium of mammary gland	UBERON:0003244	90.68	gold quality
mammary duct	UBERON:0001765	90.61	gold quality
colonic mucosa	UBERON:0000317	90.51	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.45	gold quality
cerebellar cortex	UBERON:0002129	90.24	gold quality
cerebellar hemisphere	UBERON:0002245	90.16	gold quality
germinal epithelium of ovary	UBERON:0001304	90.15	silver quality
mucosa of sigmoid colon	UBERON:0004993	89.57	gold quality
visceral pleura	UBERON:0002401	89.32	gold quality
ganglionic eminence	UBERON:0004023	89.06	gold quality
parietal pleura	UBERON:0002400	88.77	gold quality
jejunum	UBERON:0002115	88.52	gold quality
epithelium of nasopharynx	UBERON:0001951	88.43	silver quality
esophagus squamous epithelium	UBERON:0006920	87.26	gold quality
adult organism	UBERON:0007023	87.11	gold quality
nipple	UBERON:0002030	87.03	gold quality
right lobe of thyroid gland	UBERON:0001119	86.99	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ENAD-17	no	26.69
E-ANND-3	no	2.43

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

33 targeting PRAG1, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4671-3P	99.88	72.46	1045
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-8076	99.78	68.52	1170
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-5007-3P	99.51	68.14	1242
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-6083	99.47	68.73	2393
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-6840-3P	98.68	65.95	1923
HSA-MIR-2115-5P	98.66	68.07	1191
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-5011-3P	98.63	64.81	638
HSA-MIR-6830-3P	98.62	68.07	1760
HSA-MIR-6754-5P	98.60	65.54	1627
HSA-MIR-4726-3P	98.49	63.89	1385
HSA-MIR-624-3P	98.37	67.06	1067
HSA-MIR-1279	97.83	67.50	1898
HSA-MIR-7154-3P	97.65	65.02	985

Literature-anchored findings (GeneRIF, showing 11)

• Also known as SgK223, a member of the NKF3 subfamily of eukaryotic protein kinases. (PMID:12471243)
• Rnd2 regulates neurite outgrowth by functioning as the RhoA activator through Pragmin, in contrast to Rnd1 and Rnd3 inhibiting RhoA signaling (PMID:16481321)
• Pragmin as a mammalian EPIYA effector and suggests that bacterial EPIYA effectors target Pragmin to subvert SFKs for successful infection. (PMID:21873224)
• Increased expression of SgK223 occurs in PDAC, and overexpression of SgK223 in pancreatic ductal epithelial cells promotes acquisition of a migratory and invasive phenotype through enhanced JAK1/Stat3 signaling (PMID:26215634)
• Results provide evidence that NACK was strongly expressed in a subset of non-small cell lung cancer (NSCLCL) samples and interference of NACK inhibits NSCLC progression through failing to activate Notch1 signaling complexes. (PMID:26782286)
• deregulation of the Pragmin-Csk axis may induce aberrant cell migration that contributes to tumor invasion and metastasis (PMID:27116701)
• the critical role of the CH region in SgK269/SgK223 association. Importantly, although SgK269 bridged SgK223 to Grb2, it was unable to activate Stat3 or efficiently enhance migration in SgK223 knock-out cells generated by CRISPR/Cas9. (PMID:27531744)
• analysis of how the kinase fold mediates non-catalytic functions in SgK223 (PMID:29079850)
• It was discovered that pseudo-kinase pragmin uses the tyrosine kinase CSK to induce protein tyrosine phosphorylation in human cells. (PMID:29503074)
• The inhibition of Panc1 cancer cells invasion by hAMSCs secretome through suppression of tyrosine phosphorylation of SGK223 (at Y411 site), c-Src (at Y416, Y530 sites), AKT activity, and JAK1/Stat3 signaling. (PMID:35059869)
• Candidate Genes for IgA Nephropathy in Pediatric Patients: Exome-Wide Association Study. (PMID:37958966)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Prag1	ENSMUSG00000050271
rattus_norvegicus	Prag1	ENSRNOG00000011407

Paralogs (3): PINK1 (ENSG00000158828), PEAK1 (ENSG00000173517), PEAK3 (ENSG00000188305)

Protein

Protein identifiers

Inactive tyrosine-protein kinase PRAG1 — Q86YV5 (reviewed: Q86YV5)

Alternative names: PEAK1-related kinase-activating pseudokinase 1, Pragmin, Sugen kinase 223

All UniProt accessions (1): Q86YV5

UniProt curated annotations — full annotation on UniProt →

Function. Catalytically inactive protein kinase that acts as a scaffold protein. Functions as an effector of the small GTPase RND2, which stimulates RhoA activity and inhibits NGF-induced neurite outgrowth. Promotes Src family kinase (SFK) signaling by regulating the subcellular localization of CSK, a negative regulator of these kinases, leading to the regulation of cell morphology and motility by a CSK-dependent mechanism. Acts as a critical coactivator of Notch signaling.

Subunit / interactions. Homodimer. Dimerization leads to the catalytic activation of CSK. Interacts (via C-terminus) with RND2. Interacts with CSK (via SH2 domain) in a Tyr-413 phosphorylation-dependent manner; this interaction potentiates kinase activity of CSK. Interacts with PEAK1. Interacts with NOTCH1 intracellular domain (N1ICD). Forms a complex with N1ICD and MAML1, in a MAML1-dependent manner.

Subcellular location. Cytoplasm. Cell junction. Focal adhesion. Nucleus.

Post-translational modifications. Phosphorylated by CSK on Tyr-253, Tyr-365, and Tyr-413; Tyr-413 is a primary site of phosphorylation.

Domain organisation. The dimerization region encompasses helices both from the N- and C-terminal of the protein kinase domain.

Similarity. Belongs to the protein kinase superfamily.

RefSeq proteins (2): NP_001074295, NP_001356688 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR008266	Tyr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR051511	MitoQC_Scaffold_Kinases	Family

Pfam: PF07714

UniProt features (77 total): helix 17, sequence variant 14, compositionally biased region 10, strand 9, modified residue 8, mutagenesis site 8, region of interest 7, chain 1, domain 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
5VE6	X-RAY DIFFRACTION	2.95
8DGN	X-RAY DIFFRACTION	3.16

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86YV5-F1	51.17	0.18

Functional residue map

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

Post-translational modifications (8): 148, 253, 365, 413, 696, 745, 782, 826

Mutagenesis-validated functional residues (8):

Position	Phenotype
955	decreases homodimerization. abolished interaction with peak1. no effect on cell migration.
966	decreases homodimerization. abolished interaction with peak1. decreases cell migration.
1243	no effect on homodimerization. decreases oligomerization. decreases interaction with peak1.
1271	decreases homodimerization. decreases interaction with peak1.
1278	decreases homodimerization.
1282	no effect on homodimerization. decreases oligomerization. decreases interaction with peak1. no effect on cell migration.
1366	decreases homodimerization. abolished interaction with peak1. decreases cell migration.
1382	decreases homodimerization. abolished interaction with peak1. decreases cell migration.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9696270	RND2 GTPase cycle

MSigDB gene sets: 79 (showing top): GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_POSITIVE_REGULATION_OF_RHO_PROTEIN_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_NEUROGENESIS, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, VERNELL_RETINOBLASTOMA_PATHWAY_DN, ROZANOV_MMP14_TARGETS_UP, GOBP_REGULATION_OF_RHO_PROTEIN_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_NOTCH_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, CHIANG_LIVER_CANCER_SUBCLASS_INTERFERON_DN, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, GOBP_REGULATION_OF_NEURON_PROJECTION_DEVELOPMENT

GO Biological Process (7): regulation of cell shape (GO:0008360), regulation of Notch signaling pathway (GO:0008593), negative regulation of neuron projection development (GO:0010977), cell migration (GO:0016477), positive regulation of Rho protein signal transduction (GO:0035025), regulation of cell motility (GO:2000145), protein phosphorylation (GO:0006468)

GO Molecular Function (4): protein kinase activity (GO:0004672), identical protein binding (GO:0042802), protein binding (GO:0005515), ATP binding (GO:0005524)

GO Cellular Component (5): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), focal adhesion (GO:0005925), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
RHO GTPase cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell motility	2
cellular anatomical structure	2
regulation of cell morphogenesis	1
regulation of biological quality	1
Notch signaling pathway	1
regulation of signal transduction	1
regulation of neuron projection development	1
neuron projection development	1
negative regulation of cell projection organization	1
Rho protein signal transduction	1
regulation of Rho protein signal transduction	1
positive regulation of small GTPase mediated signal transduction	1
regulation of locomotion	1
regulation of cellular process	1
phosphorylation	1
protein modification process	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
protein binding	1
binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
cell-substrate junction	1
cell junction	1

Protein interactions and networks

STRING

508 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRAG1	CSK	P41240	643
PRAG1	RND2	P52198	636
PRAG1	MAML1	Q92585	495
PRAG1	RHOA	P06749	476
PRAG1	EPHA10	Q5JZY3	419
PRAG1	MTMR9	Q96QG7	414
PRAG1	S100A8	P05109	414
PRAG1	ERBIN	Q96RT1	411
PRAG1	ZDBF2	Q9HCK1	410
PRAG1	NMRK1	Q9NWW6	406
PRAG1	FAM20A	Q96MK3	390
PRAG1	MFHAS1	Q9Y4C4	386
PRAG1	VRK3	Q8IV63	381
PRAG1	RUFY1	Q96T51	375
PRAG1	PEAK3	Q6ZS72	365

IntAct

30 interactions, top by confidence:

A	B	Type	Score
ZMYND19	TNFAIP1	psi-mi:“MI:0914”(association)	0.670
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
SFN	PRAG1	psi-mi:“MI:0915”(physical association)	0.590
GRB2	ARHGEF35	psi-mi:“MI:0914”(association)	0.530
CRK	ARHGAP42	psi-mi:“MI:0914”(association)	0.530
GRB2	SH3PXD2B	psi-mi:“MI:0914”(association)	0.530
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
YWHAQ	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
Dlg4	PRAG1	psi-mi:“MI:0407”(direct interaction)	0.440
YWHAE	PRAG1	psi-mi:“MI:0915”(physical association)	0.400
HSP90AB1	PRAG1	psi-mi:“MI:0915”(physical association)	0.400
PRAG1	UBE3A	psi-mi:“MI:0915”(physical association)	0.370
CRKL	SOS1	psi-mi:“MI:0914”(association)	0.350
YWHAG	C1orf226	psi-mi:“MI:0914”(association)	0.350
CSK	LCK	psi-mi:“MI:0914”(association)	0.350
CSK	HSPB1	psi-mi:“MI:0914”(association)	0.350
YWHAG	FOXO6	psi-mi:“MI:0914”(association)	0.350
YWHAH	FOXO6	psi-mi:“MI:0914”(association)	0.350
CRKL	ARHGAP42	psi-mi:“MI:0914”(association)	0.350
NAPG	NBAS	psi-mi:“MI:0914”(association)	0.350
CREB3L2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
PPP1CC	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
PRAG1	CHGB	psi-mi:“MI:0915”(physical association)	0.000
PRAG1	PSAP	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (30): SGK223 (Affinity Capture-MS), SGK223 (Affinity Capture-MS), SGK223 (Biochemical Activity), CSK (Affinity Capture-Western), SGK223 (Affinity Capture-RNA), SGK223 (Affinity Capture-MS), CHGB (Two-hybrid), PSAP (Two-hybrid), SGK223 (Affinity Capture-MS), SGK223 (Affinity Capture-MS), SGK223 (Affinity Capture-MS), SGK223 (Proximity Label-MS), SGK223 (Affinity Capture-MS), SGK223 (Affinity Capture-MS), SGK223 (Affinity Capture-MS)

ESM2 similar proteins: A0A096MK47, A0JNH1, A6H5Y1, A6NCI8, A6NFA0, A6NGG8, B2RQL2, D3Z1D3, D3ZMK9, E9Q286, E9Q309, M0RD54, O14513, P51816, Q01613, Q03172, Q05860, Q2M2Z5, Q32LN6, Q3MHH3, Q3UXL4, Q3V0A6, Q569L8, Q571I4, Q5DTX6, Q5FW52, Q5HYW2, Q5R9I1, Q5VT06, Q5VWP3, Q60988, Q66HG9, Q68DA7, Q6P1W5, Q6P9P0, Q6PAC4, Q6PG16, Q711Q0, Q7TP36, Q7TSA6

Diamond homologs: D3ZMK9, Q571I4, Q69Z38, Q86YV5, Q9BXM7, Q9H792, D6WMX4, Q4V7Q6, E0W1I1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 30 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
Activation of BAD and translocation to mitochondria	6	175.7×	7e-11
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	6	155.0×	8e-11
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	6	155.0×	8e-11
Activation of BH3-only proteins	6	114.6×	5e-10
RHO GTPases activate PKNs	6	73.2×	7e-09
Intrinsic Pathway for Apoptosis	6	67.6×	1e-08
SARS-CoV-1-host interactions	6	40.5×	2e-07
Apoptosis	6	38.8×	3e-07

GO biological processes:

GO term	Partners	Fold	FDR
intracellular protein localization	6	25.1×	2e-05
intracellular signal transduction	5	7.6×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	373
Likely benign	34
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
59334	GRCh38/hg38 8p23.1(chr8:7411297-11961807)x1	Pathogenic

SpliceAI

1319 predictions. Top by Δscore:

Variant	Effect	Δscore
8:8319298:CAGAT:C	acceptor_gain	1.0000
8:8319301:ATC:A	acceptor_loss	1.0000
8:8319302:TC:T	acceptor_loss	1.0000
8:8319303:C:CC	acceptor_gain	1.0000
8:8319303:CTGTG:C	acceptor_loss	1.0000
8:8327708:A:AC	donor_gain	1.0000
8:8327709:C:CC	donor_gain	1.0000
8:8327709:CTTT:C	donor_gain	1.0000
8:8381414:TCA:T	donor_loss	1.0000
8:8381415:CAC:C	donor_loss	1.0000
8:8381417:C:CT	donor_loss	1.0000
8:8381417:CCTG:C	donor_gain	1.0000
8:8319299:AGAT:A	acceptor_gain	0.9900
8:8319300:GAT:G	acceptor_gain	0.9900
8:8319301:AT:A	acceptor_gain	0.9900
8:8319305:G:C	acceptor_gain	0.9900
8:8327704:ACCT:A	donor_loss	0.9900
8:8327705:CCTA:C	donor_gain	0.9900
8:8327708:A:C	donor_loss	0.9900
8:8327711:TTC:T	donor_gain	0.9900
8:8327712:T:A	donor_gain	0.9900
8:8328462:C:CC	acceptor_gain	0.9900
8:8378075:TGACC:T	acceptor_loss	0.9900
8:8378079:CTAC:C	acceptor_loss	0.9900
8:8381416:A:AC	donor_gain	0.9900
8:8381417:C:CC	donor_gain	0.9900
8:8327701:GGTAC:G	donor_loss	0.9800
8:8327709:CT:C	donor_gain	0.9800
8:8327709:CTT:C	donor_gain	0.9800
8:8327710:TTT:T	donor_gain	0.9800

AlphaMissense

9143 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:8319214:A:G	F1054S	1.000
8:8327807:A:G	F992S	1.000
8:8327817:A:G	W989R	1.000
8:8327817:A:T	W989R	1.000
8:8318923:A:G	L1151P	0.999
8:8318989:A:G	L1129P	0.999
8:8319103:A:T	I1091N	0.999
8:8319213:G:C	F1054L	0.999
8:8319213:G:T	F1054L	0.999
8:8319214:A:C	F1054C	0.999
8:8319215:A:G	F1054L	0.999
8:8327710:T:A	K1024N	0.999
8:8327710:T:G	K1024N	0.999
8:8327757:A:C	Y1009D	0.999
8:8327815:C:A	W989C	0.999
8:8327815:C:G	W989C	0.999
8:8381673:C:A	W25C	0.999
8:8381673:C:G	W25C	0.999
8:8318299:C:G	R1359P	0.998
8:8318315:A:G	W1354R	0.998
8:8318315:A:T	W1354R	0.998
8:8318584:A:G	L1264P	0.998
8:8318596:A:G	L1260P	0.998
8:8318602:C:T	G1258D	0.998
8:8318603:C:G	G1258R	0.998
8:8318610:G:C	F1255L	0.998
8:8318610:G:T	F1255L	0.998
8:8318611:A:G	F1255S	0.998
8:8318612:A:G	F1255L	0.998
8:8318977:A:G	L1133P	0.998

dbSNP variants (sampled 300 via entrez): RS1000028544 (8:8372439 A>C,T), RS1000039024 (8:8383741 A>C,G), RS1000042836 (8:8329124 G>A), RS1000081880 (8:8372685 G>A,T), RS1000095643 (8:8341581 C>A,G), RS1000121275 (8:8355072 T>G), RS1000143066 (8:8333594 G>A,C), RS1000145166 (8:8322392 G>C), RS1000153822 (8:8355418 A>G), RS1000162712 (8:8346686 C>T), RS1000207672 (8:8358640 C>A), RS1000218637 (8:8384822 C>T), RS1000279190 (8:8360549 A>T), RS1000339308 (8:8351157 G>A), RS1000347174 (8:8381910 C>G,T)

Disease associations

OMIM: gene MIM:617344 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

69 associations (top):

Study	Trait	p-value
GCST003126_4	Influenza A (H1N1) severity	6.000000e-08
GCST003485_11	Response to fenofibrate (HDL cholesterol levels)	9.000000e-06
GCST004833_4	Cervical cancer	4.000000e-06
GCST005232_129	Neuroticism	3.000000e-31
GCST005835_1	Remission after SSRI treatment in MDD or neuroticism	8.000000e-11
GCST006166_101	Diastolic blood pressure x alcohol consumption interaction (2df test)	2.000000e-12
GCST006166_63	Diastolic blood pressure x alcohol consumption interaction (2df test)	9.000000e-11
GCST006168_48	Pulse pressure x alcohol consumption interaction (2df test)	2.000000e-16
GCST006170_15	Systolic blood pressure x alcohol consumption (light vs heavy) interaction (2df test)	3.000000e-11
GCST006170_28	Systolic blood pressure x alcohol consumption (light vs heavy) interaction (2df test)	1.000000e-11
GCST006171_11	Pulse pressure x alcohol consumption (light vs heavy) interaction (2df test)	1.000000e-10
GCST006171_3	Pulse pressure x alcohol consumption (light vs heavy) interaction (2df test)	3.000000e-11
GCST006190_33	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	2.000000e-11
GCST006190_91	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	4.000000e-11
GCST006192_20	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	3.000000e-21
GCST006192_6	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	8.000000e-22
GCST006193_17	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	1.000000e-11
GCST006193_57	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	1.000000e-11
GCST006195_26	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	3.000000e-22
GCST006195_47	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	3.000000e-23
GCST006434_111	Systolic blood pressure x alcohol consumption interaction (2df test)	2.000000e-20
GCST006867_64	Type 2 diabetes	5.000000e-08
GCST006916_12	Attention deficit hyperactivity disorder	6.000000e-06
GCST007436_6	Carotid intima media thickness	9.000000e-09
GCST007565_164	Morning person	1.000000e-13
GCST007565_38	Morning person	6.000000e-14
GCST007565_41	Morning person	4.000000e-14
GCST007576_89	Chronotype	4.000000e-14
GCST007709_239	General factor of neuroticism	3.000000e-09
GCST007709_252	General factor of neuroticism	5.000000e-09

EFO canonical traits (20, from GWAS)

EFO ID	Trait name
EFO:0007743	influenza A severity measurement
EFO:0007805	HDL cholesterol change measurement
EFO:0007660	neuroticism measurement
EFO:0005658	response to selective serotonin reuptake inhibitor
EFO:0004329	alcohol drinking
EFO:0006336	diastolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0006335	systolic blood pressure
EFO:0006527	smoking status measurement
EFO:0008328	chronotype measurement
EFO:0006939	cup-to-disc ratio measurement
EFO:0008111	diet measurement
EFO:0004530	triglyceride measurement
EFO:0004644	TPE interval measurement
EFO:0004346	neuroimaging measurement
EFO:0005665	white matter hyperintensity measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0600011	Parkinson’s disease symptom measurement
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	7
Benzo(a)pyrene	increases expression, increases mutagenesis	4
Estradiol	affects expression, affects cotreatment, decreases expression, increases expression, increases reaction	4
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	increases expression, decreases expression	3
Tetrachlorodibenzodioxin	increases expression	3
Cyclosporine	decreases expression, increases expression	3
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	2
Panobinostat	affects cotreatment, increases expression	2
Doxorubicin	decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
sotorasib	decreases expression, affects cotreatment	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
2-butenal	decreases expression	1
potassium chromate(VI)	decreases expression	1
rutecarpine	decreases expression	1
coumarin	affects phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	decreases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TK87	HAP1 SGK223 (-) 1	Cancer cell line	Male
CVCL_TK88	HAP1 SGK223 (-) 2	Cancer cell line	Male
CVCL_TK89	HAP1 SGK223 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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