KNTC1

Summary

KNTC1 (kinetochore associated 1, HGNC:17255) is a protein-coding gene on chromosome 12q24.31, encoding Kinetochore-associated protein 1 (P50748). Essential component of the mitotic checkpoint, which prevents cells from prematurely exiting mitosis. It is a selective cancer dependency (DepMap: 26.6% of cell lines).

This gene encodes a protein that is one of many involved in mechanisms to ensure proper chromosome segregation during cell division. Experimental evidence indicated that the encoded protein functioned in a similar manner to that of the Drosophila rough deal protein.

Source: NCBI Gene 9735 — RefSeq curated summary.

At a glance

• GWAS associations: 21
• Clinical variants (ClinVar): 303 total
• Phenotypes (HPO): 1
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 26.6% of screened cell lines
• MANE Select transcript: NM_014708

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17255
Approved symbol	KNTC1
Name	kinetochore associated 1
Location	12q24.31
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0166, ROD
Ensembl gene	ENSG00000184445
Ensembl biotype	protein_coding
OMIM	607363
Entrez	9735

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 6 protein_coding, 5 retained_intron, 4 protein_coding_CDS_not_defined

ENST00000333479, ENST00000377192, ENST00000423927, ENST00000436959, ENST00000450485, ENST00000534995, ENST00000535186, ENST00000535410, ENST00000536625, ENST00000539013, ENST00000541427, ENST00000541466, ENST00000542727, ENST00000545065, ENST00000546125

RefSeq mRNA: 1 — MANE Select: NM_014708 NM_014708

CCDS: CCDS45002

Canonical transcript exons

ENST00000333479 — 64 exons

Exon	Start	End
ENSE00002209010	122557384	122557509
ENSE00002209876	122568261	122568372
ENSE00002213244	122576895	122577029
ENSE00002214489	122529991	122530192
ENSE00002215063	122572937	122573056
ENSE00002221281	122538339	122538454
ENSE00002226091	122539676	122539754
ENSE00002230652	122546176	122546269
ENSE00002233045	122551458	122551523
ENSE00002239754	122575800	122575899
ENSE00002240162	122549766	122549864
ENSE00002240668	122590607	122590735
ENSE00002242377	122587711	122587874
ENSE00002242398	122574282	122574380
ENSE00002244133	122561921	122561974
ENSE00002245482	122547415	122547530
ENSE00002248326	122543600	122543634
ENSE00002258322	122571025	122571126
ENSE00002263445	122584278	122584450
ENSE00002264294	122569681	122569824
ENSE00002267749	122584893	122584990
ENSE00002268157	122544159	122544269
ENSE00002271606	122591337	122591453
ENSE00002281702	122562638	122562699
ENSE00002288672	122570876	122570932
ENSE00002289789	122580603	122580670
ENSE00002291409	122575543	122575646
ENSE00002292085	122579905	122579977
ENSE00002292722	122585636	122585774
ENSE00002292932	122557600	122557689
ENSE00002294251	122551319	122551362
ENSE00002295471	122573142	122573285
ENSE00002296471	122588712	122588816
ENSE00002297509	122542050	122542127
ENSE00002307907	122551621	122551696
ENSE00002309865	122547915	122547969
ENSE00002312211	122586701	122586757
ENSE00002314430	122546622	122546674
ENSE00002314733	122577672	122577791
ENSE00002315823	122582705	122582985
ENSE00002315929	122534664	122534784
ENSE00003277906	122626205	122626396
ENSE00003460389	122603027	122603243
ENSE00003462431	122615470	122615526
ENSE00003467943	122597731	122597938
ENSE00003499379	122624598	122624688
ENSE00003534866	122602569	122602740
ENSE00003551657	122622462	122622607
ENSE00003570088	122614991	122615086
ENSE00003570241	122594276	122594385
ENSE00003582566	122601536	122601625
ENSE00003589027	122620479	122620608
ENSE00003591638	122610822	122610900
ENSE00003597931	122604564	122604637
ENSE00003615978	122605306	122605415
ENSE00003635333	122602829	122602887
ENSE00003635594	122618343	122618397
ENSE00003637769	122621881	122621970
ENSE00003638315	122613626	122613761
ENSE00003638834	122604877	122605087
ENSE00003649690	122609384	122609430
ENSE00003652047	122618482	122618545
ENSE00003662492	122613112	122613230
ENSE00003845651	122527249	122527351

Expression profiles

Bgee: expression breadth ubiquitous, 227 present calls, max score 96.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.9890 / max 748.2458, expressed in 1654 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
128519	12.3923	1566
128520	1.8841	803
128518	0.6970	377
206942	0.0157	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	96.51	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	95.09	gold quality
ventricular zone	UBERON:0003053	94.58	gold quality
right testis	UBERON:0004534	93.89	gold quality
left testis	UBERON:0004533	93.28	gold quality
testis	UBERON:0000473	91.96	gold quality
ganglionic eminence	UBERON:0004023	90.49	gold quality
embryo	UBERON:0000922	90.11	gold quality
bone marrow cell	CL:0002092	89.37	gold quality
lower esophagus mucosa	UBERON:0035834	87.58	gold quality
adrenal tissue	UBERON:0018303	87.53	gold quality
mucosa of transverse colon	UBERON:0004991	86.60	gold quality
rectum	UBERON:0001052	86.15	gold quality
spleen	UBERON:0002106	86.08	gold quality
small intestine Peyer’s patch	UBERON:0003454	85.92	gold quality
colonic epithelium	UBERON:0000397	85.15	gold quality
skin of abdomen	UBERON:0001416	84.51	gold quality
stromal cell of endometrium	CL:0002255	84.39	gold quality
esophagus mucosa	UBERON:0002469	84.33	gold quality
right uterine tube	UBERON:0001302	84.30	gold quality
skin of leg	UBERON:0001511	83.76	gold quality
secondary oocyte	CL:0000655	83.68	gold quality
calcaneal tendon	UBERON:0003701	83.59	gold quality
transverse colon	UBERON:0001157	83.22	gold quality
ectocervix	UBERON:0012249	83.12	gold quality
small intestine	UBERON:0002108	82.87	gold quality
lymph node	UBERON:0000029	82.76	gold quality
bone marrow	UBERON:0002371	82.65	gold quality
right ovary	UBERON:0002118	82.56	gold quality
left ovary	UBERON:0002119	82.47	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.02
E-GEOD-100618	no	593.77
E-GEOD-99795	no	92.17

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CRX, NRL, SP1, SP3, SP4

miRNA regulators (miRDB)

34 targeting KNTC1, 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-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-548G-3P	99.48	68.67	2159
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-4666A-5P	99.41	69.72	1887
HSA-MIR-491-5P	99.13	65.98	1468
HSA-MIR-6868-3P	98.63	69.64	2259
HSA-MIR-3145-5P	98.57	67.83	900
HSA-MIR-1248	98.47	67.54	1314
HSA-MIR-6881-5P	98.16	67.38	665
HSA-MIR-1279	97.83	67.50	1898
HSA-MIR-6742-5P	96.32	64.01	869

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 26.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 9)

• Aurora B kinase activity is required for the accumulation of tension-sensitive mitotic-checkpoint components, such as ZW10 and ROD, in order to maintain mitotic-checkpoint arrest. (PMID:18065224)
• Kinetochoreassociated protein 1 (KNTC1) is highly expressed in esophageal squamous cell carcinoma (ESCC) cell lines. Knockdown of KNTC1 effectively inhibits cell viability and increases apoptosis. (PMID:30628654)
• Knockdown of KNTC1 Inhibits the Proliferation, Migration and Tumorigenesis of Human Bladder Cancer Cells and Induces Apoptosis. (PMID:33639055)
• Kinetochore-associated protein 1 promotes the invasion and tumorigenicity of cervical cancer cells via matrix metalloproteinase-2 and matrix metalloproteinase-9. (PMID:35389773)
• shRNAmediated knockdown of KNTC1 inhibits non-small-cell lung cancer through regulating PSMB8. (PMID:35933405)
• The infertile individual analysis based on whole-exome sequencing in chinese multi-ethnic groups. (PMID:36115009)
• Silencing of KNTC1 inhibits hepatocellular carcinoma cells progression via suppressing PI3K/Akt pathway. (PMID:36273753)
• The role of KNTC1 in the regulation of proliferation, migration and tumorigenesis in colorectal cancer. (PMID:37230198)
• KNTC1 knockdown inhibits the proliferation and migration of osteosarcoma cells by MCM2. (PMID:38818892)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	kntc1	ENSDARG00000101670
mus_musculus	Kntc1	ENSMUSG00000029414
rattus_norvegicus	Kntc1	ENSRNOG00000033658
drosophila_melanogaster	rod	FBGN0003268
caenorhabditis_elegans		WBGENE00018900

Protein

Protein identifiers

Kinetochore-associated protein 1 — P50748 (reviewed: P50748)

Alternative names: Rough deal homolog

All UniProt accessions (5): P50748, E7ES84, F5H5V0, H0YFL5, J3KQF2

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.

Subunit / interactions. Interacts with ZW10; the interaction is required for stable association with the kinetochore. Component of the RZZ complex composed of KNTC1/ROD, ZW10 and ZWILCH; in the complex interacts directly with ZWILCH.

Subcellular location. Cytoplasm. Nucleus. Chromosome. Centromere. Kinetochore. Cytoskeleton. Spindle.

Tissue specificity. High expression in testis.

Isoforms (2)

UniProt ID	Names	Canonical?
P50748-1	1	yes
P50748-2	2

RefSeq proteins (1): NP_055523* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019527	RZZ-complex_KNTC1/ROD_C	Domain
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR052802	KNTC1	Family
IPR055402	KNTC1_N	Domain
IPR055403	ARM_KNTC1_1st	Domain
IPR055404	ARM_KNTC1_2nd	Domain
IPR055405	ARM_KNTC1_3rd	Domain

Pfam: PF10493, PF24506, PF24515, PF24516, PF24520

UniProt features (13 total): sequence variant 5, modified residue 4, splice variant 3, chain 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-P50748-F1	71.72	0.00

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): 13, 15, 1035, 1045

Function

Pathways and Gene Ontology

Reactome pathways

18 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
R-HSA-141424	Amplification of signal from the kinetochores
R-HSA-162582	Signal Transduction
R-HSA-1640170	Cell Cycle
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-2555396	Mitotic Metaphase and Anaphase
R-HSA-68882	Mitotic Anaphase
R-HSA-68886	M Phase
R-HSA-69278	Cell Cycle, Mitotic
R-HSA-69618	Mitotic Spindle Checkpoint
R-HSA-69620	Cell Cycle Checkpoints
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 294 (showing top): GOBP_CHROMOSOME_ORGANIZATION, WU_APOPTOSIS_BY_CDKN1A_VIA_TP53, E2F_Q4_01, GOBP_ATTACHMENT_OF_SPINDLE_MICROTUBULES_TO_KINETOCHORE, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_REGULATION_OF_NUCLEAR_DIVISION, GOBP_CHROMOSOME_LOCALIZATION, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_CHROMOSOME_SEPARATION, GOBP_REGULATION_OF_EXIT_FROM_MITOSIS, GOMF_GTPASE_BINDING, GGGTGGRR_PAX4_03, PATIL_LIVER_CANCER, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, PUJANA_CHEK2_PCC_NETWORK

GO Biological Process (7): mitotic sister chromatid segregation (GO:0000070), mitotic spindle assembly checkpoint signaling (GO:0007094), regulation of exit from mitosis (GO:0007096), cell division (GO:0051301), regulation of attachment of spindle microtubules to kinetochore (GO:0051988), protein-containing complex assembly (GO:0065003), protein localization to kinetochore involved in kinetochore assembly (GO:1903394)

GO Molecular Function (2): small GTPase binding (GO:0031267), protein binding (GO:0005515)

GO Cellular Component (13): spindle pole (GO:0000922), nucleus (GO:0005634), cytoplasm (GO:0005737), kinetochore microtubule (GO:0005828), cytosol (GO:0005829), plasma membrane (GO:0005886), actin cytoskeleton (GO:0015629), RZZ complex (GO:1990423), chromosome, centromeric region (GO:0000775), kinetochore (GO:0000776), chromosome (GO:0005694), spindle (GO:0005819), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Mitotic Prometaphase	2
M Phase	2
Cell Cycle	2
Amplification of signal from the kinetochores	1
Mitotic Anaphase	1
RHO GTPase Effectors	1
Mitotic Spindle Checkpoint	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Mitotic Metaphase and Anaphase	1
Cell Cycle, Mitotic	1
Cell Cycle Checkpoints	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membraneless organelle	4
cellular anatomical structure	3
sister chromatid segregation	1
mitotic nuclear division	1
mitotic cell cycle process	1
mitotic cell cycle	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
cellular process	1
attachment of spindle microtubules to kinetochore	1
regulation of cell cycle process	1
cellular component assembly	1
protein-containing complex organization	1
protein localization to kinetochore	1
kinetochore assembly	1
GTPase binding	1
binding	1
spindle	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
spindle microtubule	1
cytoplasm	1
membrane	1
cell periphery	1
cytoskeleton	1
kinetochore	1
protein-containing complex	1
chromosomal region	1
condensed chromosome, centromeric region	1
supramolecular complex	1
microtubule cytoskeleton	1

Protein interactions and networks

STRING

1768 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KNTC1	ZWILCH	Q9H900	996
KNTC1	ZW10	O43264	995
KNTC1	ZWINT	O95229	903
KNTC1	INCENP	Q9NQS7	729
KNTC1	CDCA8	Q53HL2	678
KNTC1	RSRC2	Q7L4I2	676
KNTC1	CDC20	Q12834	642
KNTC1	LYRM1	O43325	585
KNTC1	CDC6	Q99741	580
KNTC1	MAD2L1	Q13257	576
KNTC1	CDCA5	Q96FF9	568
KNTC1	BUB1	O43683	555
KNTC1	CENPM	Q9NSP4	520
KNTC1	BUB1B	O60566	496
KNTC1	CHAF1A	Q13111	495

IntAct

129 interactions, top by confidence:

A	B	Type	Score
RFXANK	RFXAP	psi-mi:“MI:0914”(association)	0.780
ZW10	NBAS	psi-mi:“MI:0914”(association)	0.720
SCN2B	EXOC5	psi-mi:“MI:0914”(association)	0.640
GYPA	TCAF2	psi-mi:“MI:0914”(association)	0.640
ZW10	KNTC1	psi-mi:“MI:0914”(association)	0.600
SLC16A3	CASK	psi-mi:“MI:0914”(association)	0.590
Zw10	NBAS	psi-mi:“MI:0914”(association)	0.560
Zw10	NBAS	psi-mi:“MI:0915”(physical association)	0.560
KNTC1	ZWILCH	psi-mi:“MI:0915”(physical association)	0.540
KNTC1	ZWILCH	psi-mi:“MI:0407”(direct interaction)	0.540
HTR2C	KLRG2	psi-mi:“MI:0914”(association)	0.530
TMEM108	TCAF2	psi-mi:“MI:0914”(association)	0.530
SLC15A1	METTL15	psi-mi:“MI:0914”(association)	0.530
IL13RA2	METTL15	psi-mi:“MI:0914”(association)	0.530
LAMP3	METTL15	psi-mi:“MI:0914”(association)	0.530
EPHA1	EXOC5	psi-mi:“MI:0914”(association)	0.530
SPRING1	PLSCR1	psi-mi:“MI:0914”(association)	0.530
TMEM171	THAP12	psi-mi:“MI:0914”(association)	0.530
TMEM9	ESYT2	psi-mi:“MI:0914”(association)	0.530
CXCR4	TMEM120B	psi-mi:“MI:0914”(association)	0.530

BioGRID (133): KNTC1 (Reconstituted Complex), PIAS4 (Co-localization), KNTC1 (Affinity Capture-MS), KNTC1 (Affinity Capture-MS), KNTC1 (Affinity Capture-MS), KNTC1 (Affinity Capture-MS), KNTC1 (Affinity Capture-MS), KNTC1 (Affinity Capture-MS), KNTC1 (Co-fractionation), KNTC1 (Affinity Capture-MS), KNTC1 (Affinity Capture-MS), KNTC1 (Affinity Capture-MS), KNTC1 (Affinity Capture-MS), KNTC1 (Affinity Capture-MS), KNTC1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8GXY4, A4D1P6, A8XSV3, B0JZ65, B0R160, B0WYR6, E9Q7R9, F1REV3, F6S215, O00443, O65418, P50748, Q09178, Q12769, Q17I16, Q19317, Q2TAW0, Q3MHH2, Q402B2, Q4V9P9, Q5R6T6, Q5RAY1, Q5RB52, Q5RE88, Q5ZJY3, Q5ZL79, Q5ZLL7, Q6DTM3, Q6GM71, Q6INI5, Q6P996, Q6X9E4, Q6ZQQ6, Q7TMQ7, Q86XI2, Q8BJW5, Q8BMQ2, Q8C3Y4, Q8K3E5, Q8N157

Diamond homologs: P50748, Q8C3Y4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
KNTC1	“form complex”	“RZZ complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	227
Likely benign	10
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

7983 predictions. Top by Δscore:

Variant	Effect	Δscore
12:122538334:TTCAG:T	acceptor_loss	1.0000
12:122538336:CAG:C	acceptor_loss	1.0000
12:122538337:A:AG	acceptor_gain	1.0000
12:122538337:AG:A	acceptor_loss	1.0000
12:122538338:G:GG	acceptor_gain	1.0000
12:122538338:GAT:G	acceptor_gain	1.0000
12:122538450:CTAAT:C	donor_gain	1.0000
12:122538451:TAAT:T	donor_gain	1.0000
12:122538452:AAT:A	donor_gain	1.0000
12:122538452:AATGT:A	donor_loss	1.0000
12:122538453:AT:A	donor_gain	1.0000
12:122538453:ATGT:A	donor_loss	1.0000
12:122538454:TGT:T	donor_loss	1.0000
12:122538455:G:GA	donor_loss	1.0000
12:122538455:G:GG	donor_gain	1.0000
12:122538456:T:A	donor_loss	1.0000
12:122539663:AATTT:A	acceptor_gain	1.0000
12:122539670:A:AG	acceptor_gain	1.0000
12:122539671:T:G	acceptor_gain	1.0000
12:122539672:TTA:T	acceptor_loss	1.0000
12:122539674:A:AG	acceptor_gain	1.0000
12:122539674:A:C	acceptor_loss	1.0000
12:122539674:AG:A	acceptor_gain	1.0000
12:122539675:G:GT	acceptor_gain	1.0000
12:122539675:GG:G	acceptor_gain	1.0000
12:122539675:GGC:G	acceptor_gain	1.0000
12:122539675:GGCA:G	acceptor_gain	1.0000
12:122539675:GGCAT:G	acceptor_gain	1.0000
12:122539750:TGAAG:T	donor_gain	1.0000
12:122539751:GAAG:G	donor_gain	1.0000

AlphaMissense

14563 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:122551658:G:C	A412P	0.998
12:122551671:C:A	A416D	0.998
12:122575591:T:A	W811R	0.998
12:122575591:T:C	W811R	0.998
12:122557388:T:A	V426D	0.997
12:122557639:T:A	W480R	0.997
12:122557639:T:C	W480R	0.997
12:122571031:T:A	W642R	0.997
12:122571031:T:C	W642R	0.997
12:122551629:G:C	R402P	0.996
12:122551635:T:C	L404P	0.996
12:122551668:T:C	F415S	0.996
12:122568271:T:A	W539R	0.996
12:122568271:T:C	W539R	0.996
12:122615048:T:A	W1979R	0.996
12:122615048:T:C	W1979R	0.996
12:122551670:G:C	A416P	0.995
12:122551686:T:C	L421P	0.995
12:122557496:T:C	L462P	0.995
12:122568358:T:A	W568R	0.995
12:122568358:T:C	W568R	0.995
12:122569771:T:A	W603R	0.995
12:122569771:T:C	W603R	0.995
12:122571033:G:C	W642C	0.995
12:122571033:G:T	W642C	0.995
12:122602607:A:C	R1564S	0.995
12:122602607:A:T	R1564S	0.995
12:122551621:A:C	R399S	0.994
12:122551621:A:T	R399S	0.994
12:122551659:C:A	A412D	0.994

dbSNP variants (sampled 300 via entrez): RS1000004134 (12:122615348 C>T), RS1000025534 (12:122547272 A>G,T), RS1000055210 (12:122618659 A>G), RS1000056624 (12:122547475 C>A,T), RS1000087162 (12:122595462 A>G), RS1000097634 (12:122564009 G>A), RS1000188895 (12:122576779 A>G), RS1000199451 (12:122537874 C>T), RS1000233690 (12:122608497 A>G), RS1000239613 (12:122541616 A>G), RS1000244918 (12:122589858 A>C,G), RS1000260127 (12:122547725 T>C,G), RS1000267637 (12:122528040 CAT>C), RS1000285172 (12:122535310 G>A,T), RS1000287598 (12:122553461 A>C)

Disease associations

OMIM: gene MIM:607363 | disease phenotypes:

GenCC curated gene-disease

Mondo (2): prostate cancer (MONDO:0008315), microcephaly (MONDO:0001149)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000252	Microcephaly

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST004904_90	Body mass index	3.000000e-08
GCST005312_30	Menopause (age at onset)	2.000000e-09
GCST005830_106	Hand grip strength	2.000000e-11
GCST007294_89	Body fat distribution (trunk fat ratio)	6.000000e-09
GCST007295_111	Body fat distribution (leg fat ratio)	2.000000e-12
GCST007295_95	Body fat distribution (leg fat ratio)	1.000000e-08
GCST008163_622	Height	9.000000e-06
GCST010988_505	Adult body size	4.000000e-20
GCST011122_20	Walking pace	2.000000e-09
GCST90002391_252	Mean corpuscular hemoglobin concentration	1.000000e-09
GCST90020024_244	A body shape index	5.000000e-10
GCST90020024_245	A body shape index	4.000000e-08
GCST90020025_122	Waist-to-hip ratio adjusted for BMI	1.000000e-13
GCST90020025_124	Waist-to-hip ratio adjusted for BMI	2.000000e-09
GCST90020025_26	Waist-to-hip ratio adjusted for BMI	2.000000e-10
GCST90020027_1200	Waist-hip index	5.000000e-14
GCST90020027_1201	Waist-hip index	8.000000e-09
GCST90020027_1203	Waist-hip index	8.000000e-11
GCST90020028_1240	Hip circumference adjusted for BMI	1.000000e-08
GCST90020028_1246	Hip circumference adjusted for BMI	2.000000e-10
GCST90020029_471	Waist circumference adjusted for body mass index	3.000000e-08

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004704	age at menopause
EFO:0006941	grip strength measurement
EFO:0004341	body fat distribution
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066879 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.27	Kd	54.26	nM	CHEMBL5653589
7.27	ED50	54.26	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 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	2148627: Binding affinity to human KNTC1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0543	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, decreases methylation, affects expression	5
Benzo(a)pyrene	increases expression, affects methylation, decreases expression	3
bisphenol A	decreases expression, increases expression	2
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
Resveratrol	affects cotreatment, increases expression	2
Acetaminophen	decreases expression, increases expression	2
Arsenic	increases abundance, increases methylation, affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
geraniol	decreases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
2-palmitoylglycerol	increases expression	1
K 7174	decreases expression	1
abrine	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
incobotulinumtoxinA	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Dasatinib	decreases expression	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
CHEMBL5651669	Binding	Binding affinity to human KNTC1 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)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer