ZWINT

Summary

ZWINT (ZW10 interacting kinetochore protein, HGNC:13195) is a protein-coding gene on chromosome 10q21.1, encoding Outer kinetochore KNL1 complex subunit ZWINT (O95229). Acts as a component of the outer kinetochore KNL1 complex that serves as a docking point for spindle assembly checkpoint components and mediates microtubule-kinetochore interactions. It is a selective cancer dependency (DepMap: 49.2% of cell lines).

This gene encodes a protein that is clearly involved in kinetochore function although an exact role is not known. It interacts with ZW10, another kinetochore protein, possibly regulating the association between ZW10 and kinetochores. The encoded protein localizes to prophase kinetochores before ZW10 does and it remains detectable on the kinetochore until late anaphase. It has a uniform distribution in the cytoplasm of interphase cells. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 11130 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 41 total
• Cancer dependency (DepMap): dependent in 49.2% of screened cell lines
• MANE Select transcript: NM_007057

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13195
Approved symbol	ZWINT
Name	ZW10 interacting kinetochore protein
Location	10q21.1
Locus type	gene with protein product
Status	Approved
Aliases	KNTC2AP, SIP30, Zwint1
Ensembl gene	ENSG00000122952
Ensembl biotype	protein_coding
OMIM	609177
Entrez	11130

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 27 protein_coding, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000318387, ENST00000361148, ENST00000373944, ENST00000395405, ENST00000460654, ENST00000467523, ENST00000478181, ENST00000489649, ENST00000494312, ENST00000899407, ENST00000899408, ENST00000899409, ENST00000899410, ENST00000899411, ENST00000899412, ENST00000920697, ENST00000920698, ENST00000920699, ENST00000920700, ENST00000920701, ENST00000920702, ENST00000920703, ENST00000920704, ENST00000920705, ENST00000920706, ENST00000920707, ENST00000920708, ENST00000920709, ENST00000920710, ENST00000920711, ENST00000955111, ENST00000955112

RefSeq mRNA: 3 — MANE Select: NM_007057 NM_001005413, NM_007057, NM_032997

CCDS: CCDS31205, CCDS7249

Canonical transcript exons

ENST00000373944 — 9 exons

Exon	Start	End
ENSE00000705031	56360018	56360141
ENSE00000833880	56360293	56360383
ENSE00001911939	56357227	56358185
ENSE00001932052	56361196	56361259
ENSE00003473228	56359687	56359853
ENSE00003494424	56358805	56358947
ENSE00003549145	56358556	56358724
ENSE00003549178	56358377	56358459
ENSE00003601233	56359476	56359532

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 98.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.1186 / max 406.3820, expressed in 1688 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
109420	32.1186	1688

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	98.66	gold quality
secondary oocyte	CL:0000655	98.16	gold quality
ventricular zone	UBERON:0003053	96.46	gold quality
embryo	UBERON:0000922	95.74	gold quality
endometrium epithelium	UBERON:0004811	95.09	gold quality
ganglionic eminence	UBERON:0004023	94.70	gold quality
trabecular bone tissue	UBERON:0002483	92.93	gold quality
tongue squamous epithelium	UBERON:0006919	92.76	gold quality
esophagus squamous epithelium	UBERON:0006920	92.00	gold quality
squamous epithelium	UBERON:0006914	91.82	gold quality
bone marrow	UBERON:0002371	91.81	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.74	gold quality
cervix squamous epithelium	UBERON:0006922	91.64	gold quality
rectum	UBERON:0001052	91.40	gold quality
gingival epithelium	UBERON:0001949	91.28	gold quality
epithelium of esophagus	UBERON:0001976	91.15	gold quality
mucosa of transverse colon	UBERON:0004991	91.02	gold quality
right testis	UBERON:0004534	90.27	gold quality
colonic mucosa	UBERON:0000317	90.15	gold quality
mucosa of sigmoid colon	UBERON:0004993	89.92	gold quality
left testis	UBERON:0004533	89.90	gold quality
gingiva	UBERON:0001828	89.89	gold quality
amniotic fluid	UBERON:0000173	89.88	gold quality
epithelium of nasopharynx	UBERON:0001951	89.66	gold quality
testis	UBERON:0000473	89.56	gold quality
thymus	UBERON:0002370	89.40	gold quality
vermiform appendix	UBERON:0001154	89.18	gold quality
hair follicle	UBERON:0002073	88.40	gold quality
caecum	UBERON:0001153	87.11	gold quality
oral cavity	UBERON:0000167	86.94	gold quality

Single-cell (SCXA)

Detected in 18 experiment(s), a significant marker in 16.

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	596.93
E-MTAB-6075	yes	397.52
E-HCAD-5	yes	312.97
E-GEOD-99795	yes	304.35
E-MTAB-11121	yes	220.40
E-CURD-114	yes	95.98
E-HCAD-10	yes	43.31
E-CURD-112	yes	42.28
E-MTAB-9467	yes	30.28
E-GEOD-125970	yes	24.84
E-HCAD-13	yes	21.68
E-HCAD-1	yes	19.61
E-MTAB-10553	yes	8.96
E-MTAB-6678	yes	8.51
E-ANND-3	yes	7.51

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

54 targeting ZWINT, 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-5193	100.00	67.26	1744
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-3153	99.55	67.59	2337

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 49.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 13)

• 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)
• Stable hZW10 kinetochore residency at prometaphase kinetochores is dependent on its interaction with hZwint-1, and is essential for mitotic checkpoint arrest. (PMID:18268100)
• hZwint-1 bridges the inner and outer kinetochore: identification of the kinetochore localization domain and the hZw10-interaction domain (PMID:21345172)
• These studies identify zwint-1 as a novel AurB substrate required for kinetochore assembly and for proper spindle assembly checkpoint silencing at metaphase (PMID:21775627)
• the E3 ubiquitin ligase terf causes protein degradation of ZWINT and negatively regulates cell proliferation (PMID:22023800)
• Our results provide the first evidence that Zwint-1 is required to correct erroneous kinetochore-microtubule attachment and regulate spindle checkpoint function during meiosis. (PMID:26486467)
• ZW10 interactor was frequently decreased in hepatocellular carcinoma. (PMID:30198401)
• results suggested ZWINT as a potential gene associated with lung cancer cell proliferation (PMID:30643969)
• upregulated in prostate cancer tissues (PMID:31306099)
• Anaphase-promoting complex/cyclosome-Cdc-20 promotes Zwint-1 degradation. (PMID:31945194)
• ZWINT: A potential therapeutic biomarker in patients with glioblastoma correlates with cell proliferation and invasion. (PMID:32323832)
• Genome-wide association analysis of cognitive function in Danish long-lived individuals. (PMID:33607172)
• ZWINT promotes the proliferation, migration, and invasion of cervical cancer cells by regulating the p53/p21 signaling pathway. (PMID:37929349)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zwint	ENSMUSG00000019923
rattus_norvegicus	Zwint	ENSRNOG00000048682

Protein

Protein identifiers

Outer kinetochore KNL1 complex subunit ZWINT — O95229 (reviewed: O95229)

Alternative names: ZW10 interactor, ZW10-interacting protein 1

All UniProt accessions (3): A6NH27, O95229, R4GMS7

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a component of the outer kinetochore KNL1 complex that serves as a docking point for spindle assembly checkpoint components and mediates microtubule-kinetochore interactions. Kinetochores, consisting of a centromere-associated inner segment and a microtubule-contacting outer segment, play a crucial role in chromosome segregation by mediating the physical connection between centromeric DNA and spindle microtubules. The outer kinetochore is made up of the ten-subunit KMN network, comprising the MIS12, NDC80 and KNL1 complexes, and auxiliary microtubule-associated components; together they connect the outer kinetochore with the inner kinetochore, bind microtubules, and mediate interactions with mitotic checkpoint proteins that delay anaphase until chromosomes are bioriented on the spindle. Targets the RZZ complex to the kinetochore at prometaphase. Recruits MAD2L1 to the kinetochore, but is not required for BUB1B localization. In addition to orienting mitotic chromosomes, it is also essential for alignment of homologous chromosomes during meiotic metaphase I. In meiosis I, required to activate the spindle assembly checkpoint at unattached kinetochores to correct erroneous kinetochore-microtubule attachments.

Subunit / interactions. Component of the KNL1 complex composed of KNL1 and ZWINT. Part of the ten-subunit outer kinetochore KMN network that includes the KNL1, MIS12 and NDC80 complexes; a bioriented kinetochore contains approximately 150 copies of the network. Interacts with the MIS12 complex subunits MIS12 DSN1, and PMF1. Interacts with the NDC80 complex subunit NDC80 during mitosis. Interacts with ZW10. Interacts with CETN3.

Subcellular location. Nucleus. Chromosome. Centromere. Kinetochore.

Isoforms (2)

UniProt ID	Names	Canonical?
O95229-1	1	yes
O95229-2	2

RefSeq proteins (3): NP_001005413, NP_008988, NP_127490 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029092	Zwint-1	Family

Pfam: PF15556

UniProt features (9 total): region of interest 2, sequence variant 2, chain 1, coiled-coil region 1, compositionally biased region 1, splice variant 1, helix 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8PPR	ELECTRON MICROSCOPY	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95229-F1	79.22	0.55

Function

Pathways and Gene Ontology

Reactome pathways

6 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-68877	Mitotic Prometaphase
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation

MSigDB gene sets: 397 (showing top): GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, GOBP_CHROMOSOME_ORGANIZATION, MORF_DNMT1, MODULE_52, GOBP_NEGATIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_REGULATION_OF_CELL_CYCLE_CHECKPOINT, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, KANG_DOXORUBICIN_RESISTANCE_UP, MORF_ESPL1, GNF2_CENPF, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, MORF_BUB1, GOBP_REGULATION_OF_NUCLEAR_DIVISION, CROONQUIST_NRAS_SIGNALING_DN, GOBP_REGULATION_OF_MEIOTIC_NUCLEAR_DIVISION

GO Biological Process (7): mitotic sister chromatid segregation (GO:0000070), mitotic spindle assembly checkpoint signaling (GO:0007094), homologous chromosome orientation in meiotic metaphase I (GO:0031619), cell division (GO:0051301), establishment of localization in cell (GO:0051649), regulation of meiosis I spindle assembly checkpoint (GO:1905325), mitotic cell cycle checkpoint signaling (GO:0007093)

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

GO Cellular Component (11): kinetochore (GO:0000776), outer kinetochore (GO:0000940), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), nuclear body (GO:0016604), dendrite (GO:0030425), Knl1/Spc105 complex (GO:0180019), chromosome, centromeric region (GO:0000775), nucleus (GO:0005634), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Mitotic Prometaphase	2
Amplification of signal from the kinetochores	1
Mitotic Anaphase	1
RHO GTPase Effectors	1
M Phase	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membraneless organelle	3
cellular anatomical structure	3
mitotic cell cycle process	2
mitotic cell cycle	2
protein-containing complex	2
sister chromatid segregation	1
mitotic nuclear division	1
negative regulation of mitotic metaphase/anaphase transition	1
spindle assembly checkpoint signaling	1
mitotic spindle checkpoint signaling	1
meiotic metaphase I homologous chromosome alignment	1
chromosome localization	1
cellular process	1
establishment of localization	1
cellular localization	1
regulation of meiosis I	1
regulation of spindle checkpoint	1
regulation of metaphase/anaphase transition of meiotic cell cycle	1
meiosis I spindle assembly checkpoint signaling	1
cell cycle checkpoint signaling	1
negative regulation of mitotic cell cycle	1
binding	1
condensed chromosome, centromeric region	1
supramolecular complex	1
kinetochore	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
nucleoplasm	1
neuron projection	1
dendritic tree	1
outer kinetochore	1
chromosomal region	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1364 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZWINT	ZW10	O43264	994
ZWINT	KNL1	Q8NG31	986
ZWINT	DSN1	Q9H410	949
ZWINT	NSL1	Q96IY1	935
ZWINT	KNTC1	P50748	903
ZWINT	ZWILCH	Q9H900	900
ZWINT	BUB1	O43683	895
ZWINT	PMF1	Q6P1K2	889
ZWINT	A0A087WT04	A0A087WT04	887
ZWINT	AURKB	Q96GD4	877
ZWINT	CENPF	P49454	877
ZWINT	INCENP	Q9NQS7	841
ZWINT	CENPA	P49450	825
ZWINT	BUB1B	O60566	814
ZWINT	CENPE	Q02224	761

IntAct

156 interactions, top by confidence:

A	B	Type	Score
NUF2	NDC80	psi-mi:“MI:0914”(association)	0.950
ZWINT	NDC80	psi-mi:“MI:0914”(association)	0.940
NDC80	ZWINT	psi-mi:“MI:0915”(physical association)	0.940
ZWINT	NDC80	psi-mi:“MI:0403”(colocalization)	0.940
ZWINT	NDC80	psi-mi:“MI:0915”(physical association)	0.940
NDC80	ZWINT	psi-mi:“MI:0403”(colocalization)	0.940
SPC25	NDC80	psi-mi:“MI:0914”(association)	0.940
SPC24	NDC80	psi-mi:“MI:0914”(association)	0.920
DSN1	ZWINT	psi-mi:“MI:0914”(association)	0.900
MIS12	ZWINT	psi-mi:“MI:0914”(association)	0.900
MIS12	NDC80	psi-mi:“MI:0914”(association)	0.850
STX18	NBAS	psi-mi:“MI:0914”(association)	0.810
DSN1	NDC80	psi-mi:“MI:0914”(association)	0.790
BECN1	ZWINT	psi-mi:“MI:0914”(association)	0.750
BECN1	ZWINT	psi-mi:“MI:0915”(physical association)	0.750
BECN1	ZWINT	psi-mi:“MI:0407”(direct interaction)	0.750
ZWINT	BECN1	psi-mi:“MI:0403”(colocalization)	0.750
ZWINT	BECN1	psi-mi:“MI:0915”(physical association)	0.750

BioGRID (283): ZWINT (Affinity Capture-MS), ZWINT (Affinity Capture-MS), ZWINT (Affinity Capture-MS), RRBP1 (Affinity Capture-MS), CASC5 (Affinity Capture-MS), STX18 (Affinity Capture-MS), DSN1 (Affinity Capture-MS), SPC24 (Affinity Capture-MS), NDC80 (Affinity Capture-MS), PMF1 (Affinity Capture-MS), LYRM4 (Affinity Capture-MS), MTMR6 (Affinity Capture-MS), NUF2 (Affinity Capture-MS), MIS12 (Affinity Capture-MS), NFS1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GTZ2, A6H754, A6H7E2, A6NF36, A8MYB1, O35668, O54887, O55527, O95229, P03246, P03247, P04862, P14253, P33716, P54256, P54257, P60531, P69738, Q19UN5, Q28HY7, Q28I03, Q2T9Z2, Q3TCJ8, Q5I0J4, Q5RA87, Q5RE16, Q5XIC3, Q5ZK77, Q66HB6, Q6P566, Q75MW2, Q7L3B6, Q8BGD0, Q8IYM0, Q8K389, Q8N485, Q8N6Q1, Q8NCU1, Q96SN8, Q9BE52

Diamond homologs: O95229, Q2TBH8, Q8VIL3, Q9CQU5

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
ZWINT	“form complex”	“RZZ complex”	binding
BECN1	“up-regulates activity”	ZWINT	binding
AURKB	“up-regulates activity”	ZWINT	phosphorylation
ZWINT	“form complex”	“KNL1 complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 105 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
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	14	23.6×	2e-13
Amplification of signal from the kinetochores	8	22.8×	8e-08
EML4 and NUDC in mitotic spindle formation	14	18.8×	2e-12
Mitotic Spindle Checkpoint	8	18.4×	4e-07
Resolution of Sister Chromatid Cohesion	14	17.6×	4e-12
RHO GTPases Activate Formins	14	15.8×	1e-11
Mitotic Prometaphase	14	14.0×	5e-11
Separation of Sister Chromatids	14	12.3×	3e-10

GO biological processes:

GO term	Partners	Fold	FDR
attachment of spindle microtubules to kinetochore	9	94.7×	6e-14
mitotic spindle assembly checkpoint signaling	8	50.5×	5e-10
mitotic sister chromatid segregation	7	37.9×	9e-08
chromosome segregation	7	13.7×	9e-05
intermediate filament organization	5	13.5×	3e-03
cell division	18	9.3×	2e-10
protein transport	12	5.9×	9e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	29
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

928 predictions. Top by Δscore:

Variant	Effect	Δscore
10:56358456:CAGC:C	acceptor_gain	1.0000
10:56358458:GCCT:G	acceptor_loss	1.0000
10:56358459:CCT:C	acceptor_gain	1.0000
10:56358460:C:CC	acceptor_gain	1.0000
10:56358461:T:C	acceptor_gain	1.0000
10:56358461:T:TC	acceptor_gain	1.0000
10:56358551:TTTA:T	donor_loss	1.0000
10:56358555:C:G	donor_loss	1.0000
10:56358722:TAC:T	acceptor_gain	1.0000
10:56358723:ACC:A	acceptor_loss	1.0000
10:56358724:CCTA:C	acceptor_loss	1.0000
10:56358725:CT:C	acceptor_loss	1.0000
10:56358726:T:G	acceptor_loss	1.0000
10:56358800:CTTA:C	donor_loss	1.0000
10:56358801:TTAC:T	donor_loss	1.0000
10:56358802:TA:T	donor_loss	1.0000
10:56358803:A:AC	donor_gain	1.0000
10:56358803:A:C	donor_loss	1.0000
10:56358803:AC:A	donor_gain	1.0000
10:56358803:ACCT:A	donor_gain	1.0000
10:56358804:C:CT	donor_gain	1.0000
10:56358804:CC:C	donor_gain	1.0000
10:56358804:CCT:C	donor_gain	1.0000
10:56358804:CCTC:C	donor_gain	1.0000
10:56358804:CCTCT:C	donor_gain	1.0000
10:56358945:CTC:C	acceptor_gain	1.0000
10:56358948:C:CC	acceptor_gain	1.0000
10:56358952:C:CT	acceptor_gain	1.0000
10:56358952:C:T	acceptor_gain	1.0000
10:56358953:A:T	acceptor_gain	1.0000

AlphaMissense

1807 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:56360299:A:C	F42L	0.981
10:56360299:A:T	F42L	0.981
10:56360301:A:G	F42L	0.981
10:56359824:A:G	W96R	0.976
10:56359824:A:T	W96R	0.976
10:56359822:C:A	W96C	0.970
10:56359822:C:G	W96C	0.970
10:56359810:C:A	K100N	0.961
10:56359810:C:G	K100N	0.961
10:56360104:A:G	L57P	0.951
10:56359814:A:G	L99P	0.944
10:56358712:G:C	F212L	0.932
10:56358712:G:T	F212L	0.932
10:56358714:A:G	F212L	0.932
10:56358704:A:G	L215P	0.931
10:56359823:C:G	W96S	0.931
10:56359718:A:G	L131P	0.928
10:56360086:A:G	L63P	0.925
10:56360119:A:G	L52P	0.918
10:56359831:C:A	K93N	0.917
10:56359831:C:G	K93N	0.917
10:56359836:C:G	A92P	0.916
10:56360127:T:A	K49N	0.916
10:56360127:T:G	K49N	0.916
10:56358710:A:G	L213P	0.913
10:56359697:A:G	L138P	0.910
10:56360128:T:A	K49I	0.910
10:56359803:A:C	Y103D	0.899
10:56359809:C:G	A101P	0.896
10:56359845:C:G	A89P	0.896

dbSNP variants (sampled 300 via entrez): RS1000731463 (10:56357475 T>A), RS1001325472 (10:56357401 T>C), RS1001385671 (10:56362235 A>T), RS1003099884 (10:56361443 C>A,T), RS1005209014 (10:56360239 G>A,C), RS1005446030 (10:56362085 A>C,G,T), RS1005496212 (10:56363106 C>T), RS1005548799 (10:56362870 C>G,T), RS1005882146 (10:56361479 C>T), RS1007208468 (10:56357814 A>G), RS1007280521 (10:56358128 C>T), RS1007522055 (10:56360673 G>T), RS1007574242 (10:56360419 C>T), RS1007904299 (10:56358761 C>G,T), RS1009193826 (10:56359061 G>A,T)

Disease associations

OMIM: gene MIM:609177 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST000960_4	Cardiac hypertrophy	5.000000e-07
GCST006218_100	Erosive tooth wear (severe vs non-severe)	3.000000e-06
GCST006226_11	Erosive tooth wear (severe vs none or mild)	8.000000e-08
GCST006226_2	Erosive tooth wear (severe vs none or mild)	5.000000e-06
GCST010678_3	Liver fibrosis (total hepatic collagen content)	4.000000e-06
GCST012170_2	Cognitive function in longevity	3.000000e-07
GCST012170_3	Cognitive function in longevity	3.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0002503	cardiac hypertrophy
EFO:0010576	liver fibrosis measurement
EFO:0008354	cognitive function measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	4
bisphenol A	affects expression, decreases expression, increases expression	3
Benzo(a)pyrene	decreases expression, increases expression	3
Estradiol	increases expression	3
Cyclosporine	decreases expression	3
2,3-dimethoxy-1,4-naphthoquinone	increases expression	2
Resveratrol	decreases expression, affects cotreatment, increases expression	2
Acetaminophen	decreases expression, increases expression	2
Cisplatin	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	affects expression, decreases expression	2
Valproic Acid	affects expression, decreases methylation	2
Aflatoxin B1	affects expression, decreases methylation	2
Particulate Matter	increases expression, decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
afuresertib	decreases expression	1
sotorasib	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1
propionaldehyde	decreases expression	1
arsenite	increases reaction, affects binding	1
afimoxifene	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
diallyl trisulfide	decreases expression	1
bicalutamide	decreases expression	1
polyhexamethyleneguanidine	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
perfluorooctane sulfonic acid	decreases expression	1

Clinical trials (associated diseases)

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