ZYX

Summary

ZYX (zyxin, HGNC:13200) is a protein-coding gene on chromosome 7q34, encoding Zyxin (Q15942). Adhesion plaque protein.

Focal adhesions are actin-rich structures that enable cells to adhere to the extracellular matrix and at which protein complexes involved in signal transduction assemble. Zyxin is a zinc-binding phosphoprotein that concentrates at focal adhesions and along the actin cytoskeleton. Zyxin has an N-terminal proline-rich domain and three LIM domains in its C-terminal half. The proline-rich domain may interact with SH3 domains of proteins involved in signal transduction pathways while the LIM domains are likely involved in protein-protein binding. Zyxin may function as a messenger in the signal transduction pathway that mediates adhesion-stimulated changes in gene expression and may modulate the cytoskeletal organization of actin bundles. Alternative splicing results in multiple transcript variants that encode the same isoform.

Source: NCBI Gene 7791 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 101 total
• Druggable target: yes
• MANE Select transcript: NM_003461

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13200
Approved symbol	ZYX
Name	zyxin
Location	7q34
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000159840
Ensembl biotype	protein_coding
OMIM	602002
Entrez	7791

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 14 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000322764, ENST00000354434, ENST00000392910, ENST00000436448, ENST00000446634, ENST00000449630, ENST00000457235, ENST00000468083, ENST00000477373, ENST00000497119, ENST00000869086, ENST00000869087, ENST00000869088, ENST00000869089, ENST00000869090, ENST00000943397, ENST00000943398, ENST00000943399

RefSeq mRNA: 3 — MANE Select: NM_003461 NM_001010972, NM_001362783, NM_003461

CCDS: CCDS5883

Canonical transcript exons

ENST00000322764 — 10 exons

Exon	Start	End
ENSE00001048010	143389857	143389977
ENSE00001048013	143388767	143388945
ENSE00001090664	143388489	143388658
ENSE00001090668	143382801	143383322
ENSE00001911613	143381345	143381409
ENSE00001929592	143390578	143391111
ENSE00003478275	143381557	143381779
ENSE00003501899	143382248	143382447
ENSE00003530569	143382593	143382685
ENSE00003545295	143388219	143388339

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.50.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 286.8911 / max 3665.3581, expressed in 1827 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
81772	271.8682	1827
81773	3.6282	1440
81785	3.5061	1407
81771	2.1402	752
81776	1.6995	1014
81784	1.0146	647
81774	0.7631	439
81789	0.4783	282
81788	0.4728	261
81786	0.4110	207

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of uterus	UBERON:0009853	99.50	gold quality
myometrium	UBERON:0001296	99.49	gold quality
left uterine tube	UBERON:0001303	99.38	gold quality
granulocyte	CL:0000094	99.33	gold quality
lower esophagus	UBERON:0013473	99.31	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.31	gold quality
blood	UBERON:0000178	99.30	gold quality
stromal cell of endometrium	CL:0002255	99.28	gold quality
ascending aorta	UBERON:0001496	99.26	gold quality
thoracic aorta	UBERON:0001515	99.26	gold quality
right coronary artery	UBERON:0001625	99.26	gold quality
smooth muscle tissue	UBERON:0001135	99.22	gold quality
popliteal artery	UBERON:0002250	99.21	gold quality
tibial artery	UBERON:0007610	99.21	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.21	gold quality
descending thoracic aorta	UBERON:0002345	99.18	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.16	gold quality
upper lobe of left lung	UBERON:0008952	99.15	gold quality
right lung	UBERON:0002167	99.14	gold quality
endocervix	UBERON:0000458	99.12	gold quality
left coronary artery	UBERON:0001626	99.07	gold quality
mucosa of stomach	UBERON:0001199	98.99	gold quality
urinary bladder	UBERON:0001255	98.95	gold quality
uterine cervix	UBERON:0000002	98.86	gold quality
vermiform appendix	UBERON:0001154	98.82	gold quality
ectocervix	UBERON:0012249	98.82	gold quality
leukocyte	CL:0000738	98.77	gold quality
gall bladder	UBERON:0002110	98.75	gold quality
monocyte	CL:0000576	98.73	gold quality
subcutaneous adipose tissue	UBERON:0002190	98.67	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	10.82
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, SMAD3, WT1

miRNA regulators (miRDB)

22 targeting ZYX, 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-6748-5P	100.00	65.81	1057
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-3913-3P	99.74	66.53	938
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-3944-5P	98.50	67.55	997
HSA-MIR-4483	98.09	64.12	1642
HSA-MIR-6502-3P	97.86	65.43	569
HSA-MIR-1288-3P	96.86	66.95	536
HSA-MIR-6747-5P	96.17	64.99	743
HSA-MIR-1293	96.16	64.69	916
HSA-MIR-3675-5P	95.90	65.80	474

Literature-anchored findings (GeneRIF, showing 40)

• LIM-nebulette, Lasp-1, and zyxin may play an important role in the organization of focal adhesions (PMID:15004028)
• We identified zyxin as an interactor with endoglin in human umbilical vein vascular endothelial cells and this interaction is localized within the 47-amino acid carboxyl-terminal cytosolic domain of endoglin, and maps within zyxin residues 326-572. (PMID:15084601)
• Within Ewing tumor cells, zyxin is expressed at very low levels and remains diffusely distributed throughout the cytoplasm, instead of concentrating in actin-rich dynamic structures. Zyxin has tumor suppressor activity in Ewing tumor cells. (PMID:15748890)
• zyxin indirectly enables the interaction of ZNF384/CIZ/NMP4 with p130CAS (PMID:16510139)
• A sarch for genes upregulated by thymosin beta4 identified zyxin in SiHA cells in the presence of exogenously added thymosin beta4 and when thymosin beta4 is overexpressed using adenoviral vectors. (PMID:16956606)
• These results suggest that zyxin is involved in mechanical-force-dependent facilitation of actin polymerization at focal adhesions. (PMID:18682496)
• This study establishes a crucial role of zyxin in thrombin signaling in endothelial cells and provides evidence for a novel PAR-1 signaling pathway mediated by zyxin. (PMID:19690217)
• The LIM domain protein zyxin was identified as an interaction partner for human synemin. (PMID:19853601)
• Stretch appears to be an important factor in the development of endothelial dysfunction with zyxin as a potential therapeutic target to interfere with these early changes in endothelial cell phenotype (PMID:20705921)
• Findings suggest an unforeseen role for Zyxin in DNA damage-induced cell fate control through modulating the HIPK2-p53 signaling axis. (PMID:21248071)
• Zyxin, whose expression is negatively regulated by microRNA-16 (miR-16), is confirmed to be a direct target gene of miR-16. Overexpression of zyxin could also restrain cell movement and enhance cell-cell adhesion. (PMID:21360639)
• When myosin II contractility was inhibited, the k(off) values for all three proteins changed rapidly, in a highly protein-specific manner: dissociation of vinculin from FAs was facilitated, whereas dissociation of paxillin and zyxin was attenuated. (PMID:21486952)
• LIM domain of zyxin recruits zyxin to force-bearing sites at the leading edge of migrating cells (PMID:21889443)
• Depletion of nectin-2 from L cells expressing E-cadherin results in a loss of zyxin localization to cell-cell contacts, demonstrating that the zyxin-nectin interaction plays a critical role in zyxin targeting to these sites. (PMID:22056563)
• Zyxin phenotype is mediated by partners alpha-actinin and p130Cas and ensures that motile cells in a three-dimensional matrix explore the largest space possible in minimum time. (PMID:22395610)
• Zyxin is a transforming growth factor-beta (TGF-beta)/Smad3 target gene that regulates lung cancer cell motility via integrin alpha5beta1. (PMID:22778267)
• A stretch-induced signaling pathway in vascular cells leads to the activation of zyxin, a cytoskeletal protein specifically involved in transducing mechanical stimuli. (PMID:23233529)
• Zyxin is suggested to promote growth, migration and invasiveness of fibroblastic type oral squamous cell carcinoma cells by upregulating Rac1 and Cdc42. (PMID:23292068)
• RA-induced cancer cell cytotoxicity was significantly impaired by Zyxin or PTOV1. Overall, our findings suggest that Zyxin and PTOV1 should be considered as critical determinants in cancer therapy with retinoids (PMID:23321499)
• Zyxin is a novel target for beta-amyloid peptide activities in Alzheimer’s disease. (PMID:23330981)
• Integrin-beta5 and zyxin mediate formation of ventral stress fibers in response to transforming growth factor beta. (PMID:24036928)
• Zyxin, which is thought to be essential for tight cell-to-cell junctions, decreased 1.8-fold in TNF-alpha-treated human brain microvascular endothelial cells. (PMID:25025691)
• Matrix density alters zyxin phosphorylation, which limits peripheral process formation and extension in endothelial cells invading 3D collagen matrices. (PMID:25038525)
• ZYX gene may be aging-related gene and involved in Osteoporosis. (PMID:25771989)
• key regulator of stretch-induced gene expression at the cellular level (PMID:26071033)
• VASP, zyxin and TES are tension-dependent members of focal adherens junctions independent of the alpha-catenin-vinculin module. (PMID:26611125)
• Zyxin binding to Ptc2 is due to the interaction of Zyxin 2nd LIM-domain (530-590 aa) with the under-membrane region of the cytoplasmic C-terminus of Ptc2 (1159-1412 aa). (PMID:27125030)
• Study findings identify zyxin as a physiological regulator of endothelial exocytosis through reorganizing local actin network in the final stage of exocytosis. Zyxin downregulation inhibits the secretion of VWF from human primary endothelial cells. (PMID:28256511)
• Increased zyxin expression is associated with asthma. (PMID:28278518)
• Zyxin promotes MAVS-mediated IFNB1 promoter activation. (PMID:28928438)
• these observations suggest that Zyxin promotes colon cancer tumorigenesis in a mitotic-phosphorylation-dependent manner and through CDK8-mediated YAP activation. (PMID:29967145)
• Zyxin (ZYX) promotes invasion and acts as a biomarker for aggressive phenotypes of human glioblastoma multiforme. (PMID:31949244)
• Force-responsive Zyxin modulation in periodontal ligament cells is regulated by YAP rather than TAZ. (PMID:32330602)
• Cell density-dependent proteolysis by HtrA1 induces translocation of zyxin to the nucleus and increased cell survival. (PMID:32826880)
• Bioinformatic Analysis of Structure and Function of LIM Domains of Human Zyxin Family Proteins. (PMID:33808029)
• Essential role of zyxin in platelet biogenesis and glycoprotein Ib-IX surface expression. (PMID:34657146)
• Expression of Zyxin in Non-Small Cell Lung Cancer-A Preliminary Study. (PMID:35740950)
• Enhancement of Zyxin Promotes Skin Fibrosis by Regulating FAK/PI3K/AKT and TGF-beta Signaling Pathways via Integrins. (PMID:37215989)
• Zyxin promotes hepatocellular carcinoma progression via the activation of AKT/mTOR signaling pathway. (PMID:37547758)
• Zyxin is important for the stability and function of podocytes, especially during mechanical stretch. (PMID:38605154)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	zyx	ENSDARG00000075733
mus_musculus	Zyx	ENSMUSG00000029860
rattus_norvegicus	Zyx	ENSRNOG00000017354
caenorhabditis_elegans		WBGENE00006839

Paralogs (1): TRIP6 (ENSG00000087077)

Protein

Protein identifiers

Zyxin — Q15942 (reviewed: Q15942)

Alternative names: Zyxin-2

All UniProt accessions (6): Q15942, C9IZ41, C9JJK5, H0Y2Y8, H7C3D3, H7C3R3

UniProt curated annotations — full annotation on UniProt →

Function. Adhesion plaque protein. Binds alpha-actinin and the CRP protein. Important for targeting TES and ENA/VASP family members to focal adhesions and for the formation of actin-rich structures. May be a component of a signal transduction pathway that mediates adhesion-stimulated changes in gene expression.

Subunit / interactions. Interacts with HPV type 6 protein E6. Does not interact significantly with E6 proteins from HPV types 11, 16, or 18. Interacts, via the Pro-rich regions, with the EVH1 domains of ENAH, EVL and VASP. Interacts with the first LIM domain of TES. Interacts with NEBL (isoform 2). Interacts with SYNPO2. (Microbial infection) Interacts with human papillomavirus type 6/HPV6 protein E6. Does not interact significantly with E6 proteins from HPV types 11, 16, or 18.

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

Similarity. Belongs to the zyxin/ajuba family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q15942-1	1	yes
Q15942-2	2

RefSeq proteins (3): NP_001010972, NP_001349712, NP_003452* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001781	Znf_LIM	Domain

Pfam: PF00412

UniProt features (39 total): modified residue 19, compositionally biased region 8, mutagenesis site 4, domain 3, initiator methionine 1, chain 1, splice variant 1, sequence variant 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15942-F1	63.57	0.19

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 (19): 2, 116, 142, 143, 169, 170, 179, 253, 259, 265, 267, 270, 272, 274, 279, 281, 288, 308, 344

Mutagenesis-validated functional residues (4):

Position	Phenotype
71	reduced interaction with enah and vasp.
93	reduced interaction with enah and vasp.
104	greatly reduced interaction with enah and vasp; when associated with a-71 or with a-71 and a-93.
114	no targeting to focal adhesions and reduced actin-rich structures; when associated with a-71; a-93 and a-104.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 301 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, MODULE_52, MODULE_92, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, MACLACHLAN_BRCA1_TARGETS_DN, BASSO_B_LYMPHOCYTE_NETWORK, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_RESPONSE_TO_PEPTIDE, MODULE_45, WEIGEL_OXIDATIVE_STRESS_BY_TBH_AND_H2O2, MODULE_16, NAGASHIMA_NRG1_SIGNALING_UP, HUMMERICH_SKIN_CANCER_PROGRESSION_DN, GOBP_CELL_CELL_SIGNALING, MODULE_118

GO Biological Process (7): cell-matrix adhesion (GO:0007160), transforming growth factor beta receptor signaling pathway (GO:0007179), integrin-mediated signaling pathway (GO:0007229), cell-cell signaling (GO:0007267), stress fiber assembly (GO:0043149), cellular response to type II interferon (GO:0071346), cell adhesion (GO:0007155)

GO Molecular Function (3): RNA binding (GO:0003723), metal ion binding (GO:0046872), protein binding (GO:0005515)

GO Cellular Component (11): stress fiber (GO:0001725), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), adherens junction (GO:0005912), focal adhesion (GO:0005925), actin cytoskeleton (GO:0015629), phagocytic vesicle (GO:0045335), cytoskeleton (GO:0005856), anchoring junction (GO:0070161)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cell-substrate adhesion	1
cellular response to transforming growth factor beta stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
cell surface receptor signaling pathway	1
cell communication	1
signaling	1
contractile actin filament bundle assembly	1
actomyosin structure organization	1
response to type II interferon	1
cellular response to cytokine stimulus	1
cellular process	1
nucleic acid binding	1
cation binding	1
binding	1
actomyosin	1
contractile actin filament bundle	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1
cell-cell junction	1
cell-substrate junction	1
cytoskeleton	1
endocytic vesicle	1
intracellular membraneless organelle	1
cell junction	1

Protein interactions and networks

STRING

1776 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZYX	VCL	P18206	999
ZYX	VASP	P50552	999
ZYX	TLN1	Q9Y490	999
ZYX	TLN2	Q9Y4G6	999
ZYX	PXN	P49023	990
ZYX	BCAR1	P56945	939
ZYX	PTK2	Q05397	934
ZYX	SYNM	O15061	875
ZYX	SRC	P12931	849
ZYX	LASP1	Q14847	823
ZYX	LATS1	O95835	795
ZYX	ILK	P57043	728
ZYX	BLOC1S6	Q9UL45	724
ZYX	EVL	Q9UI08	708
ZYX	CSRP3	P50461	706

IntAct

201 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
IMP3	ZYX	psi-mi:“MI:0915”(physical association)	0.830
ZYX	IMP3	psi-mi:“MI:0915”(physical association)	0.830
VASP	ZYX	psi-mi:“MI:0915”(physical association)	0.800
ZYX	PHF21A	psi-mi:“MI:0915”(physical association)	0.740
PHF21A	ZYX	psi-mi:“MI:0915”(physical association)	0.740
RTN4IP1	ZYX	psi-mi:“MI:0915”(physical association)	0.740
ZYX	RTN4IP1	psi-mi:“MI:0915”(physical association)	0.740
VASP	CEP43	psi-mi:“MI:0914”(association)	0.740
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
ZYX	EVL	psi-mi:“MI:0915”(physical association)	0.700
TUFT1	ZYX	psi-mi:“MI:0915”(physical association)	0.670
ZYX	CASS4	psi-mi:“MI:0915”(physical association)	0.670
ZYX	ENAH	psi-mi:“MI:0915”(physical association)	0.670
VCAM1	ITGB1	psi-mi:“MI:0914”(association)	0.660
LPXN	PCNT	psi-mi:“MI:0914”(association)	0.640
NME5	ZYX	psi-mi:“MI:0915”(physical association)	0.600

BioGRID (410): LIN7A (Two-hybrid), PDLIM5 (Two-hybrid), PHF21A (Two-hybrid), IMP3 (Two-hybrid), YPEL3 (Two-hybrid), RTN4IP1 (Two-hybrid), ZYX (Two-hybrid), ZYX (Reconstituted Complex), ZYX (Affinity Capture-MS), ZYX (Affinity Capture-MS), CD2AP (Co-fractionation), ZYX (Co-fractionation), ZYX (Co-fractionation), ZYX (Co-fractionation), ZYX (Co-fractionation)

ESM2 similar proteins: A1X283, A2AAY5, A5D7F8, A5GFW5, A6ND36, D3ZIE4, D3ZUI5, E2RP94, M0R4F8, O15117, O35601, O54967, O75128, O89032, Q04584, Q06649, Q07912, Q13094, Q13625, Q15942, Q17R10, Q17R13, Q1LYG0, Q32LQ1, Q3TC93, Q3UH68, Q498M5, Q4KM52, Q5DTU0, Q5JV73, Q5NBX1, Q5TCZ1, Q5U2X5, Q62523, Q6IQ23, Q6TXD4, Q80TI1, Q8BI17, Q8BZI0, Q8CG79

Diamond homologs: A1ZA47, A2ALU4, A5H447, D4A702, E1BKA3, O00151, O14639, O43294, O60711, O70209, O70400, O75112, O94929, P20271, P48059, P49023, P49024, P50464, P52944, Q09476, Q0WSN2, Q13796, Q15942, Q1JQB5, Q2KJ33, Q2TCH4, Q2YDK0, Q3MHZ4, Q3SX26, Q3SX40, Q3SYZ8, Q3T0X8, Q3TJD7, Q55BI0, Q5F464, Q5R7I1, Q5RCF7, Q5TD97, Q5U2Z2, Q5XI07

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
AKT1	down-regulates	ZYX	phosphorylation
AKT	down-regulates	ZYX	phosphorylation
CDK1	“up-regulates activity”	ZYX	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 144 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
Signaling by Hippo	5	29.9×	4e-04

GO biological processes:

GO term	Partners	Fold	FDR
protein phosphorylation	10	5.7×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	81
Likely benign	8
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1797 predictions. Top by Δscore:

Variant	Effect	Δscore
7:143388477:T:A	acceptor_gain	1.0000
7:143388478:G:A	acceptor_gain	1.0000
7:143388485:CCAGA:C	acceptor_loss	1.0000
7:143388486:CA:C	acceptor_loss	1.0000
7:143388487:A:AG	acceptor_gain	1.0000
7:143388487:AGAAC:A	acceptor_loss	1.0000
7:143388488:G:GG	acceptor_gain	1.0000
7:143388488:GA:G	acceptor_gain	1.0000
7:143388488:GAA:G	acceptor_gain	1.0000
7:143388655:CACTG:C	donor_loss	1.0000
7:143388656:ACT:A	donor_gain	1.0000
7:143388656:ACTG:A	donor_loss	1.0000
7:143388657:CT:C	donor_gain	1.0000
7:143388658:TGTGA:T	donor_loss	1.0000
7:143388659:G:GC	donor_loss	1.0000
7:143388659:G:GG	donor_gain	1.0000
7:143388660:T:A	donor_loss	1.0000
7:143388762:CTCAG:C	acceptor_loss	1.0000
7:143388763:TCA:T	acceptor_loss	1.0000
7:143388765:A:AG	acceptor_gain	1.0000
7:143388765:AG:A	acceptor_gain	1.0000
7:143388766:G:A	acceptor_loss	1.0000
7:143388766:G:GG	acceptor_gain	1.0000
7:143388766:GG:G	acceptor_gain	1.0000
7:143388766:GGA:G	acceptor_gain	1.0000
7:143388766:GGAC:G	acceptor_gain	1.0000
7:143388943:CAA:C	donor_gain	1.0000
7:143388946:GTGA:G	donor_loss	1.0000
7:143388951:G:GT	donor_gain	1.0000
7:143389852:TCCA:T	acceptor_loss	1.0000

AlphaMissense

3693 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:143388614:T:C	F424L	1.000
7:143388616:C:A	F424L	1.000
7:143388616:C:G	F424L	1.000
7:143388782:T:A	C444S	1.000
7:143388782:T:C	C444R	1.000
7:143388783:G:C	C444S	1.000
7:143388854:T:C	F468L	1.000
7:143388855:T:C	F468S	1.000
7:143388856:C:A	F468L	1.000
7:143388856:C:G	F468L	1.000
7:143388860:T:C	C470R	1.000
7:143388861:G:A	C470Y	1.000
7:143388862:T:G	C470W	1.000
7:143388869:T:C	C473R	1.000
7:143388896:T:C	F482L	1.000
7:143388897:T:C	F482S	1.000
7:143388898:C:A	F482L	1.000
7:143388898:C:G	F482L	1.000
7:143388926:T:C	C492R	1.000
7:143388927:G:A	C492Y	1.000
7:143388928:T:G	C492W	1.000
7:143389873:T:A	C504S	1.000
7:143389873:T:C	C504R	1.000
7:143389874:G:C	C504S	1.000
7:143389875:C:G	C504W	1.000
7:143389951:T:C	F530L	1.000
7:143389952:T:C	F530S	1.000
7:143389952:T:G	F530C	1.000
7:143389953:C:A	F530L	1.000
7:143389953:C:G	F530L	1.000

dbSNP variants (sampled 300 via entrez): RS1000019148 (7:143381249 T>C), RS1000033513 (7:143387966 A>G), RS1001786095 (7:143388058 C>T), RS1002274320 (7:143386484 G>A), RS1002560859 (7:143381476 T>G), RS1002604748 (7:143387675 C>G,T), RS1003202274 (7:143389217 G>A,T), RS1003609207 (7:143384028 A>G), RS1003746643 (7:143384283 G>A,T), RS1003892264 (7:143391340 C>CAG), RS1003928781 (7:143385552 G>GTGTGAT), RS1004089148 (7:143380881 G>A), RS1004405265 (7:143385905 A>C), RS1004427554 (7:143390073 G>A), RS1005159723 (7:143391050 C>G,T)

Disease associations

OMIM: gene MIM:602002 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST004618_12	White blood cell count (basophil)	3.000000e-09
GCST007827_20	Alzheimer’s disease or HDL levels (pleiotropy)	1.000000e-10
GCST90002379_104	Basophil count	3.000000e-57
GCST90002380_49	Basophil percentage of white cells	4.000000e-55
GCST90002393_73	Monocyte count	3.000000e-17
GCST90002394_313	Monocyte percentage of white cells	7.000000e-11

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0005090	basophil count
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0007992	basophil percentage of leukocytes
EFO:0005091	monocyte count
EFO:0007989	monocyte percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295832 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cisplatin	decreases response to substance, affects cotreatment, decreases expression	3
Hydrogen Peroxide	affects expression, decreases expression, increases expression	3
Aflatoxin B1	affects expression, decreases methylation	3
Particulate Matter	increases expression, affects cotreatment, decreases expression, increases abundance	3
bisphenol A	affects expression, increases expression	2
sodium arsenite	affects binding, increases reaction, increases expression	2
cobaltous chloride	decreases expression, increases expression	2
Air Pollutants	increases expression, decreases expression, increases abundance	2
Doxorubicin	affects expression	2
Estradiol	increases expression	2
Nickel	increases expression	2
Smoke	decreases expression, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Valproic Acid	affects expression, decreases expression	2
Cadmium Chloride	increases expression	2
tert-Butylhydroperoxide	affects expression, decreases expression	2
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
lead acetate	increases expression	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects expression, affects response to substance	1
pyrogallol 1,3-dimethyl ether	affects localization, decreases expression, increases expression, affects cotreatment	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, decreases reaction	1
sodium bichromate	decreases expression	1
nickel subsulfide	decreases expression	1
cupric chloride	increases expression	1
coumarin	increases phosphorylation	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4232648	Binding	Binding affinity to ZYX cysteine residue in human 786-O cell soluble proteomic lysate at 5 uM incubated for 1 hr followed by cell lysis by IA-alkyne probe based isoTOP-ABPP analysis	Covalent inhibitors of nicotinamide N-methyltransferase (NNMT) provide evidence for target engagement challenges in situ. — Bioorg Med Chem Lett

Cellosaurus cell lines

3 cell lines: 2 transformed cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3LQ	Abcam HEK293T ZYX KO 2	Transformed cell line	Female
CVCL_B9W1	Abcam HEK293T ZYX KO 1	Transformed cell line	Female
CVCL_F1SM	HyCyte NK-92 KO-hZYX	Cancer cell line	Male

Clinical trials (associated diseases)

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