ZW10

Summary

ZW10 (zw10 kinetochore protein, HGNC:13194) is a protein-coding gene on chromosome 11q23.2, encoding Centromere/kinetochore protein zw10 homolog (O43264). Essential component of the mitotic checkpoint, which prevents cells from prematurely exiting mitosis. It is a selective cancer dependency (DepMap: 26.8% of cell lines).

This gene encodes a protein that is one of many involved in mechanisms to ensure proper chromosome segregation during cell division. This protein is an essential component of the mitotic checkpoint, which prevents cells from prematurely exiting mitosis.

Source: NCBI Gene 9183 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 111 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 26.8% of screened cell lines
• MANE Select transcript: NM_004724

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13194
Approved symbol	ZW10
Name	zw10 kinetochore protein
Location	11q23.2
Locus type	gene with protein product
Status	Approved
Aliases	KNTC1AP
Ensembl gene	ENSG00000086827
Ensembl biotype	protein_coding
OMIM	603954
Entrez	9183

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 2 nonsense_mediated_decay

ENST00000200135, ENST00000535142, ENST00000538209, ENST00000898960, ENST00000898961, ENST00000936157, ENST00000946662

RefSeq mRNA: 1 — MANE Select: NM_004724 NM_004724

CCDS: CCDS8363

Canonical transcript exons

ENST00000200135 — 16 exons

Exon	Start	End
ENSE00000747318	113747531	113747713
ENSE00000747322	113760209	113760368
ENSE00000747324	113760513	113760590
ENSE00000747325	113760817	113760918
ENSE00000930586	113736620	113736822
ENSE00000930587	113737572	113737703
ENSE00000930588	113738264	113738394
ENSE00000930589	113739213	113739382
ENSE00000930590	113741694	113741765
ENSE00000930591	113743802	113744040
ENSE00001130190	113733187	113733814
ENSE00001210656	113768833	113768967
ENSE00002241311	113773562	113773692
ENSE00003636877	113758554	113758706
ENSE00003641773	113757662	113757853
ENSE00003683396	113748257	113748420

Expression profiles

Bgee: expression breadth ubiquitous, 234 present calls, max score 86.87.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.3611 / max 201.7010, expressed in 1792 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
122353	16.0991	1790
122354	0.2280	75
122355	0.0340	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibialis anterior	UBERON:0001385	86.87	silver quality
ventricular zone	UBERON:0003053	86.70	gold quality
secondary oocyte	CL:0000655	86.62	gold quality
ileal mucosa	UBERON:0000331	85.44	gold quality
gastrocnemius	UBERON:0001388	85.26	gold quality
calcaneal tendon	UBERON:0003701	85.17	gold quality
muscle of leg	UBERON:0001383	84.86	gold quality
cartilage tissue	UBERON:0002418	84.81	gold quality
skin of leg	UBERON:0001511	84.00	gold quality
ganglionic eminence	UBERON:0004023	83.43	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.29	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.98	gold quality
skin of abdomen	UBERON:0001416	82.54	gold quality
rectum	UBERON:0001052	82.37	gold quality
body of pancreas	UBERON:0001150	82.22	gold quality
zone of skin	UBERON:0000014	82.21	gold quality
hindlimb stylopod muscle	UBERON:0004252	81.98	gold quality
adrenal tissue	UBERON:0018303	81.84	gold quality
oocyte	CL:0000023	81.83	gold quality
islet of Langerhans	UBERON:0000006	81.80	gold quality
stromal cell of endometrium	CL:0002255	81.44	gold quality
monocyte	CL:0000576	81.25	gold quality
esophagus mucosa	UBERON:0002469	81.21	gold quality
upper leg skin	UBERON:0004262	81.20	gold quality
leukocyte	CL:0000738	81.02	gold quality
mononuclear cell	CL:0000842	81.02	gold quality
pancreas	UBERON:0001264	80.99	gold quality
embryo	UBERON:0000922	80.92	gold quality
mucosa of transverse colon	UBERON:0004991	80.35	gold quality
minor salivary gland	UBERON:0001830	80.27	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.26

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA3

miRNA regulators (miRDB)

24 targeting ZW10, 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-150-5P	99.99	66.69	1976
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-4753-5P	99.54	68.51	1356
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-302A-5P	99.39	68.21	1913
HSA-MIR-6507-3P	99.35	67.32	1059
HSA-MIR-2116-5P	99.32	69.34	1273
HSA-MIR-6828-5P	99.31	69.21	1433
HSA-MIR-16-2-3P	99.29	70.60	1954
HSA-MIR-195-3P	99.29	70.61	1954
HSA-MIR-3160-5P	99.28	69.07	1938
HSA-MIR-1264	99.25	66.81	1317
HSA-MIR-3978	99.24	68.39	2201
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-7854-3P	99.08	66.26	1117
HSA-MIR-3926	98.95	69.26	1438
HSA-MIR-4703-5P	98.53	70.13	1645
HSA-MIR-3942-5P	98.52	69.51	1517
HSA-MIR-6792-3P	98.41	66.86	1359
HSA-MIR-6892-5P	97.27	68.60	847

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 26.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 13)

• Overexpression, microinjection and knockdown experiments revealed that ZW10 is involved in membrane trafficking between the endoplasmic reticulum and Golgi (PMID:15029241)
• show that ZW10 interacting protein-1(Zwint-1) is required and is sufficient for kinetochore localization of Zeste White 10 (ZW10) in HeLa cells (PMID:15485811)
• ZW10 serves as a general regulator of dynein function throughout the cell cycle. (PMID:16505164)
• RINT-1 coordinates the localization and function of ZW10 by serving as a link between ZW10 and the SNARE complex comprising syntaxin 18. (PMID:16571679)
• targeting of ZW10 to the perinuclear Golgi region was found to depend on the perinuclear accumulation of dynactin (PMID:17560939)
• RNAi-mediated depletion of ZW10 markedly-reduced congression efficiency. (PMID:17680027)
• Rab6 regulates distinct Golgi trafficking pathways involving two separate protein complexes: ZW10/RINT-1 and COG. (PMID:17699596)
• Accumulation of ZW10 at tensionless kinetochores stems from a 4-fold reduction of kinetochore turnover rate and requires aurora B kinase activity. (PMID:18065224)
• Stable hZW10 kinetochore residency at prometaphase kinetochores is dependent on its interaction with hZwint-1, and is essential for mitotic checkpoint arrest. (PMID:18268100)
• The interaction between ZW10 and dynamitin showed that the N-terminal region of ZW10 is the major binding site for dynamitin and, like full-length ZW10, could move along microtubules to the centrosomal area in a dynein-dynactin-dependent manner. (PMID:18782227)
• Results together suggest that NAG links between p31 and ZW10-RINT-1 and is involved in Golgi-to-ER transport. (PMID:19369418)
• hZwint-1 bridges the inner and outer kinetochore: identification of the kinetochore localization domain and the hZw10-interaction domain (PMID:21345172)
• The RZZ complex was purified to homogeneity and subjected to systemic crystallization. (PMID:25849506)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	zw10	ENSDARG00000018738
mus_musculus	Zw10	ENSMUSG00000032264
rattus_norvegicus	Zw10	ENSRNOG00000054479
drosophila_melanogaster	Zw10	FBGN0004643
caenorhabditis_elegans		WBGENE00017643

Protein

Protein identifiers

Centromere/kinetochore protein zw10 homolog — O43264 (reviewed: O43264)

All UniProt accessions (2): O43264, F5H3C1

UniProt curated annotations — full annotation on UniProt →

Function. Essential component of the mitotic checkpoint, which prevents cells from prematurely exiting mitosis. Required for the assembly of the dynein-dynactin and MAD1-MAD2 complexes onto kinetochores. Its function related to the spindle assembly machinery is proposed to depend on its association in the mitotic RZZ complex. Involved in regulation of membrane traffic between the Golgi and the endoplasmic reticulum (ER); the function is proposed to depend on its association in the interphase NRZ complex which is believed to play a role in SNARE assembly at the ER.

Subunit / interactions. Interacts with NBAS and KNTC1/ROD; the interactions are mutually exclusive and indicative for its association in two different vesicle tethering complexes. Component of the RZZ complex composed of KNTC1/ROD, ZW10 and ZWILCH. Component of the NRZ complex composed of NBAS, ZW10 and RINT1/TIP20L; NRZ associates with SNAREs STX18, USE1L, BNIP1/SEC20L and SEC22B (the assembly has been described as syntaxin 18 complex). Interacts directly with RINT1/TIP20L bound to BNIP1/SEC20L. Interacts with C19orf25 and ZWINT. Interacts with ZFYVE1. Interacts with RAB18 and this interaction is enhanced in the presence of ZFYVE1.

Subcellular location. Cytoplasm. Endoplasmic reticulum membrane. Chromosome. Centromere. Kinetochore. Cytoskeleton. Spindle. Lipid droplet.

Tissue specificity. Widely expressed.

Miscellaneous. Overexpression as well as silencing of ZW10 disrupts the morphology of the ER-Golgi intermediate compartment as well as the Golgi apparatus and slows down ER-Golgi transport.

Similarity. Belongs to the ZW10 family.

Isoforms (2)

UniProt ID	Names	Canonical?
O43264-1	1	yes
O43264-2	2

RefSeq proteins (1): NP_004715* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009361	Zw10_N	Domain
IPR046362	Zw10/DSL1_C_sf	Homologous_superfamily
IPR048343	ZW10_C	Domain
IPR048344	Zw10_middle	Domain
IPR055148	ZW10_C_2	Domain

Pfam: PF06248, PF20665, PF20666, PF22766

UniProt features (11 total): modified residue 4, region of interest 2, initiator methionine 1, chain 1, sequence variant 1, coiled-coil region 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7QPG	ELECTRON MICROSCOPY	3.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43264-F1	81.29	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.

Post-translational modifications (4): 2, 3, 12, 777

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2500257	Resolution of Sister Chromatid Cohesion
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-6811434	COPI-dependent Golgi-to-ER retrograde traffic
R-HSA-68877	Mitotic Prometaphase
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation

MSigDB gene sets: 238 (showing top): GOBP_CHROMOSOME_ORGANIZATION, GOBP_ESTABLISHMENT_OF_SPINDLE_ORIENTATION, GOBP_ATTACHMENT_OF_SPINDLE_MICROTUBULES_TO_KINETOCHORE, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_REGULATION_OF_NUCLEAR_DIVISION, GOBP_SPINDLE_LOCALIZATION, GOBP_CHROMOSOME_LOCALIZATION, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_CHROMOSOME_SEPARATION, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_REGULATION_OF_EXIT_FROM_MITOSIS, REACTOME_MEMBRANE_TRAFFICKING, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_ESTABLISHMENT_OF_CELL_POLARITY, GOBP_ENDOPLASMIC_RETICULUM_TO_GOLGI_VESICLE_MEDIATED_TRANSPORT

GO Biological Process (16): mitotic sister chromatid segregation (GO:0000070), establishment of mitotic spindle orientation (GO:0000132), endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum (GO:0006890), Golgi organization (GO:0007030), mitotic metaphase chromosome alignment (GO:0007080), mitotic spindle assembly checkpoint signaling (GO:0007094), regulation of exit from mitosis (GO:0007096), protein transport (GO:0015031), protein localization to kinetochore (GO:0034501), cell division (GO:0051301), meiotic cell cycle (GO:0051321), regulation of attachment of spindle microtubules to kinetochore (GO:0051988), protein-containing complex assembly (GO:0065003), mitotic cell cycle (GO:0000278), vesicle-mediated transport (GO:0016192)

GO Molecular Function (2): centromeric DNA binding (GO:0019237), protein binding (GO:0005515)

GO Cellular Component (16): kinetochore (GO:0000776), spindle pole (GO:0000922), nucleus (GO:0005634), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), lipid droplet (GO:0005811), kinetochore microtubule (GO:0005828), cytosol (GO:0005829), membrane (GO:0016020), Dsl1/NZR complex (GO:0070939), RZZ complex (GO:1990423), chromosome, centromeric region (GO:0000775), chromosome (GO:0005694), cytoplasm (GO:0005737), spindle (GO:0005819), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Mitotic Prometaphase	2
Amplification of signal from the kinetochores	1
Mitotic Anaphase	1
RHO GTPase Effectors	1
Golgi-to-ER retrograde transport	1
M Phase	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membraneless organelle	5
cellular anatomical structure	4
mitotic cell cycle	3
cytoplasm	3
mitotic nuclear division	2
mitotic cell cycle process	2
Golgi vesicle transport	2
transport	2
cellular process	2
cell cycle	2
intracellular membrane-bounded organelle	2
sister chromatid segregation	1
establishment of mitotic spindle localization	1
establishment of spindle orientation	1
intercellular transport	1
intracellular transport	1
organelle organization	1
endomembrane system organization	1
mitotic sister chromatid segregation	1
metaphase chromosome alignment	1
negative regulation of mitotic metaphase/anaphase transition	1
spindle assembly checkpoint signaling	1
mitotic spindle checkpoint signaling	1
exit from mitosis	1
regulation of mitotic cell cycle phase transition	1
intracellular protein localization	1
establishment of protein localization	1
protein localization to chromosome, centromeric region	1
protein localization to condensed chromosome	1
sexual reproduction	1
reproductive process	1
meiotic nuclear division	1
attachment of spindle microtubules to kinetochore	1
regulation of cell cycle process	1
cellular component assembly	1
protein-containing complex organization	1
sequence-specific double-stranded DNA binding	1
binding	1
condensed chromosome, centromeric region	1
supramolecular complex	1

Protein interactions and networks

STRING

1730 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZW10	ZWILCH	Q9H900	999
ZW10	RINT1	Q6NUQ1	997
ZW10	KNTC1	P50748	995
ZW10	ZWINT	O95229	994
ZW10	ZNF787	Q6DD87	945
ZW10	DCTN2	Q13561	911
ZW10	INCENP	Q9NQS7	909
ZW10	RAB18	Q9NP72	876
ZW10	STX18	Q9P2W9	873
ZW10	BUB3	O43684	852
ZW10	BUB1	O43683	843
ZW10	SPDL1	Q96EA4	835
ZW10	BUB1B	O60566	817
ZW10	CENPE	Q02224	812
ZW10	DSN1	Q9H410	792

IntAct

199 interactions, top by confidence:

A	B	Type	Score
ZWINT	NDC80	psi-mi:“MI:0914”(association)	0.940
RINT1	ZW10	psi-mi:“MI:0915”(physical association)	0.890
RINT1	NBAS	psi-mi:“MI:0914”(association)	0.830
STX18	NBAS	psi-mi:“MI:0914”(association)	0.810
NBAS	ZW10	psi-mi:“MI:0914”(association)	0.720
ZW10	NBAS	psi-mi:“MI:0914”(association)	0.720
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710

BioGRID (204): ZW10 (Two-hybrid), ZW10 (Reconstituted Complex), ZW10 (Affinity Capture-MS), ZW10 (Affinity Capture-MS), ZW10 (Affinity Capture-MS), ZW10 (Affinity Capture-MS), ZW10 (Affinity Capture-MS), ACTR1A (Co-fractionation), ACTR1B (Co-fractionation), HSPA4 (Co-fractionation), KNTC1 (Co-fractionation), MSH2 (Co-fractionation), ZW10 (Affinity Capture-MS), ZW10 (Affinity Capture-MS), ZW10 (Affinity Capture-MS)

ESM2 similar proteins: A0JN62, A2RT67, A4IFB6, E1C3P4, F1QEB7, F1R7R1, O35099, O43264, O54921, O94967, P48553, P51593, Q08CL8, Q08CZ0, Q0VEJ0, Q28G25, Q3TLI0, Q4R350, Q5F3K0, Q5R9R1, Q5RFM4, Q5XH48, Q5XIA4, Q5ZIW2, Q641K1, Q6DE97, Q6NU53, Q6VNB8, Q7TMY8, Q7TSG1, Q7Z6Z7, Q8BH15, Q8CGF6, Q8IWR0, Q8IY22, Q8IZQ1, Q8K1X1, Q8N960, Q8QFR2, Q95LL7

Diamond homologs: O43264, O54692, Q4V8C2, Q5RFM4

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
ZW10	“form complex”	“RZZ complex”	binding
ZW10	“up-regulates activity”	DCTN2	relocalization
ZW10	“form complex”	“NRZ complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 154 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
COPI-dependent Golgi-to-ER retrograde traffic	10	11.7×	6e-06
Amplification of signal from the kinetochores	5	10.4×	6e-03
RHOQ GTPase cycle	5	9.5×	7e-03
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	7	8.6×	4e-03
COPI-mediated anterograde transport	7	8.1×	4e-03
EML4 and NUDC in mitotic spindle formation	7	6.8×	6e-03
RHO GTPases Activate Formins	8	6.5×	4e-03
Resolution of Sister Chromatid Cohesion	7	6.4×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	11	28.3×	1e-10
mitotic spindle assembly checkpoint signaling	6	25.7×	5e-05
intra-Golgi vesicle-mediated transport	5	20.1×	1e-03
endoplasmic reticulum to Golgi vesicle-mediated transport	9	9.3×	2e-04
protein transport	13	4.4×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	96
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2145 predictions. Top by Δscore:

Variant	Effect	Δscore
11:113736614:ACAT:A	donor_loss	1.0000
11:113736616:ATAC:A	donor_loss	1.0000
11:113736617:TA:T	donor_loss	1.0000
11:113736618:A:AC	donor_gain	1.0000
11:113736619:C:CC	donor_gain	1.0000
11:113736619:CCGAT:C	donor_gain	1.0000
11:113736769:CATCA:C	acceptor_gain	1.0000
11:113736774:C:CC	acceptor_gain	1.0000
11:113736829:T:C	acceptor_gain	1.0000
11:113736832:C:CT	acceptor_gain	1.0000
11:113737566:CCTTA:C	donor_loss	1.0000
11:113737567:CTTA:C	donor_loss	1.0000
11:113737568:TTA:T	donor_loss	1.0000
11:113737569:TACC:T	donor_loss	1.0000
11:113737570:A:AG	donor_loss	1.0000
11:113738260:CTAC:C	donor_loss	1.0000
11:113738262:A:AC	donor_gain	1.0000
11:113738262:ACCTG:A	donor_gain	1.0000
11:113738263:C:CC	donor_gain	1.0000
11:113738263:C:CT	donor_loss	1.0000
11:113738263:CCTG:C	donor_gain	1.0000
11:113738263:CCTGC:C	donor_gain	1.0000
11:113738266:G:A	donor_gain	1.0000
11:113738283:G:A	donor_gain	1.0000
11:113738390:TGTCC:T	acceptor_gain	1.0000
11:113738391:GTCC:G	acceptor_gain	1.0000
11:113738392:TCC:T	acceptor_gain	1.0000
11:113738393:CC:C	acceptor_gain	1.0000
11:113738393:CCCTA:C	acceptor_gain	1.0000
11:113738394:CCTA:C	acceptor_gain	1.0000

AlphaMissense

5152 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:113733739:A:C	F765L	0.999
11:113733739:A:T	F765L	0.999
11:113733741:A:G	F765L	0.999
11:113737670:A:G	W640R	0.999
11:113737670:A:T	W640R	0.999
11:113739213:C:A	G585W	0.999
11:113739334:G:C	N544K	0.999
11:113739334:G:T	N544K	0.999
11:113743873:A:C	S480R	0.999
11:113743873:A:T	S480R	0.999
11:113743875:T:G	S480R	0.999
11:113733721:T:A	R771S	0.998
11:113733721:T:G	R771S	0.998
11:113737690:A:G	L633P	0.998
11:113739337:G:C	N543K	0.998
11:113739337:G:T	N543K	0.998
11:113739350:G:T	A539D	0.998
11:113747571:G:T	A411D	0.998
11:113747572:C:G	A411P	0.998
11:113733722:C:G	R771T	0.997
11:113737657:A:G	L644P	0.997
11:113733813:A:G	W741R	0.996
11:113733813:A:T	W741R	0.996
11:113738394:C:T	G585E	0.996
11:113739213:C:G	G585R	0.996
11:113739213:C:T	G585R	0.996
11:113739333:A:G	C545R	0.996
11:113747559:A:C	M415R	0.996
11:113747567:T:A	R412S	0.996
11:113747567:T:G	R412S	0.996

dbSNP variants (sampled 300 via entrez): RS1000228374 (11:113740853 G>A,C), RS1000273690 (11:113764535 G>A), RS1000519907 (11:113741102 AC>A), RS1000521652 (11:113757369 A>G), RS1000531373 (11:113732836 C>T), RS1000559 (11:113774495 G>A,T), RS1000655419 (11:113738734 T>C), RS1000664495 (11:113769244 A>C,T), RS1000771414 (11:113768988 A>G), RS1000785870 (11:113771344 G>A), RS1000864709 (11:113745085 C>T), RS1000971766 (11:113752338 C>G), RS1001126796 (11:113759409 C>T), RS1001198413 (11:113737730 G>A,T), RS1001212085 (11:113768518 T>A,C,G)

Disease associations

OMIM: gene MIM:603954 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006701_17	Parental longevity (father’s attained age)	6.000000e-09
GCST011100_15	Aging traits (healthspan, parental lifespan or longevity) (multivariate analysis)	4.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007796	parental longevity
EFO:0009762	healthspan

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067040 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.26	Kd	54.37	nM	CHEMBL5653589
7.26	ED50	54.37	nM	CHEMBL5653589
5.54	Kd	2901	nM	CHEMBL3752910
5.54	ED50	2901	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149819: Binding affinity to human ZW10 incubated for 45 mins by Kinobead based pull down assay	kd	0.0544	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149819: Binding affinity to human ZW10 incubated for 45 mins by Kinobead based pull down assay	kd	2.9013	uM

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
2,3-dimethoxy-1,4-naphthoquinone	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
bisphenol B	increases expression	1
jinfukang	decreases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1
Quercetin	decreases expression	1
Ribonucleotides	affects binding	1
Rotenone	decreases expression	1
Tretinoin	decreases expression	1
Cyclosporine	increases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652861	Binding	Binding affinity to human ZW10 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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