YES1

Summary

YES1 (YES proto-oncogene 1, Src family tyrosine kinase, HGNC:12841) is a protein-coding gene on chromosome 18p11.32, encoding Tyrosine-protein kinase Yes (P07947). Non-receptor protein tyrosine kinase that is involved in the regulation of cell growth and survival, apoptosis, cell-cell adhesion, cytoskeleton remodeling, and differentiation.

This gene is the cellular homolog of the Yamaguchi sarcoma virus oncogene. The encoded protein has tyrosine kinase activity and belongs to the src family of proteins. This gene lies in close proximity to thymidylate synthase gene on chromosome 18, and a corresponding pseudogene has been found on chromosome 22.

Source: NCBI Gene 7525 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 75 total
• GTEx eGene: eQTL in 33 tissues, sQTL in 5 (q < 0.05)
• Drug target: yes — 1 curated mechanism-of-action drug, 5 via a complex or family; 66 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
• Approved drugs acting on a complex or family including it: 1 — Dasatinib Anhydrous (SRC)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.75 (unconstrained)
• MANE Select transcript: NM_005433
• Notable: 75 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12841
Approved symbol	YES1
Name	YES proto-oncogene 1, Src family tyrosine kinase
Location	18p11.32
Locus type	gene with protein product
Status	Approved
Aliases	Yes, c-yes, HsT441
Ensembl gene	ENSG00000176105
Ensembl biotype	protein_coding
OMIM	164880
Entrez	7525

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 23 protein_coding, 5 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000314574

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 3: 1, TSL 4: 1, TSL 5: 1

ENST00000314574, ENST00000577611, ENST00000577961, ENST00000581960, ENST00000584307, ENST00000892684, ENST00000892685, ENST00000892686, ENST00000892687, ENST00000892688, ENST00000892689, ENST00000925072, ENST00000925073, ENST00000925074, ENST00000925075, ENST00000925076, ENST00000925077, ENST00000925078, ENST00000925079, ENST00000925080, ENST00000945836, ENST00000945837, ENST00000945838, ENST00000945839, ENST00000978960, ENST00001019592, ENST00001019593, ENST00001019594, ENST00001019595, ENST00001111220

RefSeq mRNA: 1 — MANE Select: NM_005433 NM_005433

CCDS: CCDS11824

Canonical transcript exons

ENST00000314574 — 12 exons

Exon	Start	End
ENSE00001214226	732834	732965
ENSE00001214236	736808	736961
ENSE00001214245	739735	739811
ENSE00001214251	742918	743097
ENSE00001214256	743260	743415
ENSE00001214274	745948	746051
ENSE00001214283	747920	748018
ENSE00001214293	751705	751804
ENSE00001542048	721588	724632
ENSE00001665786	745708	745857
ENSE00002704426	812114	812242
ENSE00003596873	756557	756835

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 98.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 34.8243 / max 343.0358, expressed in 1669 samples.

Highest expression (Bgee): secondary oocyte, oocyte, jejunal mucosa, parotid gland, buccal mucosa cell.

Genetic regulation across tissues (GTEx eQTL / sQTL)

YES1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 33 tissues and its splicing (sQTL) in 5 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 38 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	eqtl	1.0e-11	-0.21	18:812660:G:T
Testis	eqtl	2.1e-11	-0.16	18:803838:T:G
Colon Sigmoid	eqtl	4.3e-08	+0.19	18:809504:T:C
Cells Cultured fibroblasts	sqtl	1.4e-07	-0.35	18:819810:C:T
Esophagus Muscularis	eqtl	2.1e-07	+0.13	18:668258:C:T
Brain Putamen basal ganglia	eqtl	2.7e-07	+0.18	18:805558:C:G
Esophagus Mucosa	eqtl	3.4e-07	-0.19	18:714580:C:T
Thyroid	eqtl	2.4e-06	+0.13	18:763918:G:A
Nerve Tibial	eqtl	3.5e-06	-0.20	18:710146:T:A
Brain Caudate basal ganglia	eqtl	7.8e-06	+0.14	18:819810:C:T
Brain Hypothalamus	eqtl	1.4e-05	+0.16	18:784547:G:A
Spleen	eqtl	1.6e-04	+0.18	18:813553:G:A
Adipose Subcutaneous	eqtl	1.8e-04	-0.11	18:818334:G:GA
Brain Spinal cord cervical c-1	eqtl	1.8e-04	+0.27	18:803577:C:G
Adipose Subcutaneous	sqtl	2.8e-04	+0.33	18:813659:C:CT
Brain Cortex	eqtl	3.2e-04	+0.13	18:805558:C:G
Brain Hippocampus	eqtl	3.6e-04	-0.16	18:825470:A:G
Artery Tibial	eqtl	9.1e-04	-0.17	18:732165:A:AC
Adrenal Gland	eqtl	1.2e-03	+0.17	18:761127:G:A
Brain Amygdala	eqtl	1.3e-03	+0.23	18:811699:G:A

FANTOM5 promoters

4 alternative TSS:

Promoter ID	TPM avg	Samples expressed
170952	29.6834	1659
170953	4.2716	1411
170954	0.5509	267
170955	0.3185	146

Top tissues by expression

showing 100 of 298 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.57	gold quality
oocyte	CL:0000023	98.42	gold quality
jejunal mucosa	UBERON:0000399	97.17	gold quality
parotid gland	UBERON:0001831	96.75	gold quality
buccal mucosa cell	CL:0002336	96.73	gold quality
visceral pleura	UBERON:0002401	96.55	gold quality
gingival epithelium	UBERON:0001949	96.47	gold quality
esophagus squamous epithelium	UBERON:0006920	96.43	gold quality
parietal pleura	UBERON:0002400	96.18	gold quality
pleura	UBERON:0000977	96.12	gold quality
endothelial cell	CL:0000115	96.09	gold quality
gingiva	UBERON:0001828	96.01	gold quality
squamous epithelium	UBERON:0006914	96.00	gold quality
corpus epididymis	UBERON:0004359	95.69	gold quality
mammary duct	UBERON:0001765	95.46	gold quality
oral cavity	UBERON:0000167	95.37	gold quality
skin of hip	UBERON:0001554	95.26	gold quality
epithelium of mammary gland	UBERON:0003244	95.24	gold quality
lower lobe of lung	UBERON:0008949	95.24	gold quality
nephron tubule	UBERON:0001231	95.18	gold quality
mucosa of sigmoid colon	UBERON:0004993	95.12	gold quality
choroid plexus epithelium	UBERON:0003911	95.03	gold quality
amniotic fluid	UBERON:0000173	94.91	gold quality
tibia	UBERON:0000979	94.74	gold quality
epithelium of esophagus	UBERON:0001976	94.71	gold quality
renal glomerulus	UBERON:0000074	94.70	gold quality
cartilage tissue	UBERON:0002418	94.65	gold quality
colonic mucosa	UBERON:0000317	94.54	gold quality
periodontal ligament	UBERON:0008266	94.50	gold quality
metanephric glomerulus	UBERON:0004736	94.48	gold quality
pericardium	UBERON:0002407	94.42	gold quality
placenta	UBERON:0001987	94.35	gold quality
palpebral conjunctiva	UBERON:0001812	94.33	gold quality
upper leg skin	UBERON:0004262	94.20	gold quality
renal medulla	UBERON:0000362	94.18	gold quality
germinal epithelium of ovary	UBERON:0001304	94.16	gold quality
kidney epithelium	UBERON:0004819	94.10	gold quality
mammalian vulva	UBERON:0000997	94.09	gold quality
adrenal tissue	UBERON:0018303	93.87	gold quality
eye	UBERON:0000970	93.72	gold quality
cervix squamous epithelium	UBERON:0006922	93.69	gold quality
penis	UBERON:0000989	93.57	gold quality
tongue squamous epithelium	UBERON:0006919	93.30	gold quality
mammary gland	UBERON:0001911	93.25	gold quality
thoracic mammary gland	UBERON:0005200	93.21	gold quality
seminal vesicle	UBERON:0000998	93.15	gold quality
duodenum	UBERON:0002114	93.09	gold quality
cauda epididymis	UBERON:0004360	93.05	gold quality
caput epididymis	UBERON:0004358	93.00	gold quality
jejunum	UBERON:0002115	92.96	gold quality
epithelium of nasopharynx	UBERON:0001951	92.88	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.82	gold quality
epithelial cell of pancreas	CL:0000083	92.69	gold quality
endometrium	UBERON:0001295	92.61	gold quality
pylorus	UBERON:0001166	92.50	gold quality
mucosa of urinary bladder	UBERON:0001259	92.26	gold quality
ventricular zone	UBERON:0003053	92.18	gold quality
oviduct epithelium	UBERON:0004804	92.04	gold quality
nasal cavity mucosa	UBERON:0001826	91.87	gold quality
metanephros	UBERON:0000081	91.76	gold quality
pharyngeal mucosa	UBERON:0000355	91.76	gold quality
islet of Langerhans	UBERON:0000006	91.71	gold quality
calcaneal tendon	UBERON:0003701	91.69	gold quality
superficial temporal artery	UBERON:0001614	91.65	gold quality
pigmented layer of retina	UBERON:0001782	91.56	gold quality
retina	UBERON:0000966	91.54	gold quality
cardia of stomach	UBERON:0001162	91.47	gold quality
synovial joint	UBERON:0002217	91.17	gold quality
nasal cavity epithelium	UBERON:0005384	90.93	gold quality
liver	UBERON:0002107	90.90	gold quality
medial globus pallidus	UBERON:0002477	90.66	gold quality
cervix epithelium	UBERON:0004801	90.60	gold quality
hair follicle	UBERON:0002073	90.45	gold quality
cortex of kidney	UBERON:0001225	90.39	gold quality
cranial nerve II	UBERON:0000941	90.21	gold quality
rectum	UBERON:0001052	90.16	gold quality
blood vessel layer	UBERON:0004797	90.06	gold quality
kidney	UBERON:0002113	89.90	gold quality
saphenous vein	UBERON:0007318	89.90	gold quality
globus pallidus	UBERON:0001875	89.89	gold quality
adipose tissue	UBERON:0001013	89.83	gold quality
colonic epithelium	UBERON:0000397	89.82	gold quality
connective tissue	UBERON:0002384	89.73	gold quality
ganglionic eminence	UBERON:0004023	89.73	gold quality
embryo	UBERON:0000922	89.68	gold quality
tendon	UBERON:0000043	89.65	gold quality
urethra	UBERON:0000057	89.58	gold quality
lung	UBERON:0002048	89.54	gold quality
stromal cell of endometrium	CL:0002255	89.36	gold quality
pancreas	UBERON:0001264	89.01	gold quality
heart right ventricle	UBERON:0002080	88.73	gold quality
corpus callosum	UBERON:0002336	88.65	gold quality
bronchial epithelial cell	CL:0002328	88.64	gold quality
uterus	UBERON:0000995	88.63	gold quality
gall bladder	UBERON:0002110	88.58	gold quality
fallopian tube	UBERON:0003889	88.51	gold quality
upper arm skin	UBERON:0004263	88.42	gold quality
adipose tissue of abdominal region	UBERON:0007808	88.15	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.13	gold quality
smooth muscle tissue	UBERON:0001135	87.89	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.16
E-MTAB-7381	no	58.50
E-CURD-112	no	3.30

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Liver	tissue	47.3	low
Placenta	tissue	39.1	medium
Kidney	tissue	26.1	medium
Spleen	tissue	25.8	not detected
Olfactory bulb	tissue	25.5
Pancreas	tissue	25.0	medium
Adipose tissue	tissue	23.6	medium
Duodenum	tissue	23.3	medium
Small intestine	tissue	22.3	medium
Esophagus	tissue	21.3	low
Rectum	tissue	21.3	medium
Thyroid gland	tissue	20.6	medium
Breast	tissue	20.4	medium
Colon	tissue	20.4	medium
Stomach 1	tissue	20.1	medium
Salivary gland	tissue	19.7	low
Urinary bladder	tissue	19.0	medium
Parathyroid gland	tissue	18.8	medium
Testis	tissue	17.7	medium
Gallbladder	tissue	17.7	medium
Epididymis	tissue	16.9	medium
Cervix	tissue	16.4	medium
Lung	tissue	16.2	medium
Skin 1	tissue	15.8	medium
Hippocampus	tissue	15.3	medium
Choroid plexus	tissue	15.2
Endometrium 1	tissue	15.0	low
Smooth muscle	tissue	14.8	low
Ovary	tissue	14.6	medium
Prostate	tissue	14.1	medium
Locus coeruleus	tissue	13.9
Tongue	tissue	13.7
Fallopian tube	tissue	13.0	medium
Adrenal gland	tissue	12.7	medium
Nucleus accumbens	tissue	12.5
Heart muscle	tissue	12.3	medium
Hippocampal formation	tissue	11.7
Spinal cord	tissue	11.3
Seminal vesicle	tissue	11.2	medium
Postcentral gyrus	tissue	11.2
Vagina	tissue	11.0	low
Putamen	tissue	10.7
Thalamus	tissue	10.4
Amygdala	tissue	10.2
Midbrain	tissue	10.0
Ventral forebrain	tissue	9.9
Appendix	tissue	9.9	medium
Basal ganglia	tissue	9.8	medium
Thymus	tissue	9.8
Superior colliculi	tissue	9.7
Caudate putamen	tissue	9.7
Septum	tissue	9.6
Medulla oblongata	tissue	9.4
Substantia nigra	tissue	9.4
Pons	tissue	9.2
Frontal cortex	tissue	8.7
Cerebellum	tissue	8.6	medium
Tonsil	tissue	8.3	medium
Periaqueductal gray	tissue	8.3
Entorhinal cortex	tissue	8.1

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Posterior thalamic nucleus (21.5), Cervical spinal cord, ventral horn (21.1), Area postrema (20.5), Supraoptic nucleus (20.1), Cerebellar white matter (19.8).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR1, NANOG

miRNA regulators (miRDB)

Targeting YES1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 190 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-590-3P	99.96	74.34	6478

Functional genomics

gnomAD constraint: pLI 1.81e-05, LOEUF 0.751, missense Z 1.97 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000314574 splits into 2 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
18:724,427–756,562	385 / 540.9	0.71	no
18:756,563–756,827	110 / 104.0	1.06	no

Literature-anchored findings (GeneRIF, showing 40)

• cAMP activates while Ca(2+) inhibits human sperm c-yes kinase activity (PMID:12080032)
• QM binds to c-yes at the SH3 domain in tumor cell lines (PMID:12138090)
• This review summarizes the potential functions of c-Yes and its ability to modulate signals that are distinct from c-Src. (PMID:12456296)
• Src family kinase Yes triggers hyperosmotic activation of the epidermal growth factor receptor and CD95 (PMID:15039424)
• activation of c-Yes is important for maintaining embryonic stem cells in an undifferentiated state (PMID:15148312)
• c-Yes 3’-UTR contains at least three newly identified adenine/uridine-rich elements (AREs) which are bound specifically by ARE-binding proteins HuR and AUF1. (PMID:16289864)
• Vascular endothelial growth factor (VEGF)-induced cell migration is significantly decreased in Yes-deficient retinal microvascular endothelial cells. (PMID:16400523)
• NFAT1, a transcription factor connected with breast cancer metastasis, is activated by Wnt-5a through a Ca2+ signaling pathway in human breast epithelial cells which was simultaneously counteracted by a Wnt-5a-induced Yes/Cdc42 signaling pathway. (PMID:16880514)
• activation of the protooncogene product c-Yes may play a significant role in the malignant transformation of hepatocytes (PMID:17007035)
• The results were confirmed at the level of mRNA and protein, and suggested that four genes (OPCML, RNASE1, YES1 and ACK1) could play a key role in the tumorigenesis and metastasis of gastric cancer. (PMID:17109515)
• Nucleus-located c-Yes may be a useful marker to detect early-stage hepatocellular carcinoma. (PMID:17143518)
• Amyloid aggregation by an SH3 domain from the Src family. (PMID:17418139)
• Thus, these results suggest that endogenous c-Src, c-Yes, and Lyn are differentially activated through Cdc2 activation during M phase. (PMID:17692281)
• c-Yes induction results in increased colorectal carcinoma cell motility but did not promote proliferation. In later stages of colorectal carcinogenesis, elevations in c-Yes levels/activity may promote cancer spread & metastasis rather than tumor growth. (PMID:17898870)
• Binding of CD95 Ligand to CD95 on glioblastoma cells recruit Yes and the p85 subunit of phosphatidylinositol 3-kinase to CD95, which signal invasion via the glycogen synthase kinase 3-beta pathway and subsequent expression of matrix metalloproteinases. (PMID:18328427)
• These results suggest that SFK trafficking is specified by the palmitoylation state in the SH4 domain. (PMID:19258394)
• Cloning of the complete coding sequence of the cDNA of the Csk and Yes tyrosine kinases genes of the human lymphocytes and retina have been carried out. (PMID:19757166)
• Data show that found that IFIH1, a susceptibility gene of type 1 diabetes, interacts with YES1, which plays a role in glucose transport. (PMID:19797678)
• Study identified the previously reported pathogenic mutation of NTRK3 in a KRAS/BRAF wild-type tumor and 2 somatic mutations in the Src family of kinases (YES1 and LYN) that would be expected to cause structural changes. (PMID:19893451)
• Both YES and STAT1 were verified as direct miR-145 targets (PMID:20098684)
• c-Yes was expressed in malignant melanoma, and squamous cell carcinoma type skin neoplasms. (PMID:20796316)
• Yes-associated protein may play important roles in different pathways in distinct lung tumor subtypes. (PMID:21190720)
• c-Yes regulates specific oncogenic signalling pathways important for colon cancer progression that is not shared with c-Src. (PMID:21390316)
• Functional activation of Src family kinase yes protein is essential for the enhanced malignant properties of human melanoma cells expressing ganglioside GD3. (PMID:21454696)
• Taken together, our findings demonstrate that Yes and Lyn phosphorylate EGFR at Y1101, which influences EGFR nuclear translocation in this model of cetuximab resistance. (PMID:22430206)
• study concludes that Yes is a central mediator for malignant mesothelioma cell growth that is not shared with other Src family kinases such as c-Src (PMID:22948717)
• we identified CRKL/YES as critical interrelated pathways necessary for rhabdomyosarcoma cell growth and survival and suggest a potential therapeutic role of SRC family kinase inhibition in the treatment of rhabdomyosarcoma. (PMID:23318429)
• Expression of HPV type 16 E7 resulted in increase in Src and Yes proteins level, but did not alter the level of Fyn. (PMID:23497302)
• YES1 and YAP transcript levels were higher in liver metastases of patients with colon cancer after 5FU-based neoadjuvant chemotherapy. (PMID:24323901)
• YES kinase as a proximal glucose-specific signal in the Cdc42-signaling cascade. (PMID:24610809)
• Results demonstrate a unique role for Yes in phosphorylation of FAK and in promoting PCa metastasis. Therefore, phosphorylated FAK Y861 and increased Yes expression may be predictive markers for PCa metastasis. (PMID:25868388)
• findings indicate that miR-203 induces the apoptosis of KB cells by directly targeting Yes-1, suggesting its application in anti-cancer therapeutics (PMID:25910964)
• Increased YES/SFK activation might serve as a clinical biomarker for predicting tumor resistance to IGF-1R inhibition. (PMID:25925378)
• Up-regulation of miR-210 inhibits hepatocellular carcinoma cell proliferation. Yes1 is a target of miR-210 and affects cell proliferation in HCC. (PMID:26676187)
• Our results suggest that H19 functions as a competitive endogenous RNA (ceRNA) by acting as a sink for miR-17-5p, revealing a potential ceRNA regulatory network involving H19 and miR-17-5p with a role in the modulation of YES1 expression (PMID:27093644)
• c-Yes plays an important role in migration and invasion of epithelial ovarian cancer. (PMID:27289010)
• Study on the role of miR-140-5p in inhibiting tumorigenesis in gastric cancer thru targeting YES proto-oncogene 1(YES1). (PMID:28818100)
• The downregulation of miR-199a contributes to paclitaxel (PTX) resistance in prostate cancer. YES1 mediates the regulation of miR-199a in prostate cancer PTX resistance. (PMID:29204706)
• findings identify acquired amplification of YES1 as a recurrent and targetable mechanism of resistance to EGFR inhibition in EGFR-mutant lung cancers and demonstrate the utility of transposon mutagenesis in discovering clinically relevant mechanisms of drug resistance. (PMID:29875142)
• YES1 is essential for NSCLC carcinogenesis. YES1 overexpression induced metastatic spread in preclinical in vivo models. YES1 genetic depletion by CRISPR/Cas9 technology significantly reduced tumor growth and metastasis. (PMID:31166114)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	yes1	ENSDARG00000005941
mus_musculus	Yes1	ENSMUSG00000014932
rattus_norvegicus	Yes1	ENSRNOG00000037227

Paralogs (32): FGR (ENSG00000000938), MATK (ENSG00000007264), BTK (ENSG00000010671), FYN (ENSG00000010810), STYK1 (ENSG00000060140), TNK2 (ENSG00000061938), TXK (ENSG00000074966), JAK2 (ENSG00000096968), ABL1 (ENSG00000097007), PTK6 (ENSG00000101213), HCK (ENSG00000101336), BMX (ENSG00000102010), CSK (ENSG00000103653), TYK2 (ENSG00000105397), JAK3 (ENSG00000105639), FRK (ENSG00000111816), ITK (ENSG00000113263), ZAP70 (ENSG00000115085), PTK2B (ENSG00000120899), SRMS (ENSG00000125508), TEC (ENSG00000135605), BLK (ENSG00000136573), ABL2 (ENSG00000143322), FER (ENSG00000151422), JAK1 (ENSG00000162434), SYK (ENSG00000165025), PTK2 (ENSG00000169398), TNK1 (ENSG00000174292), FES (ENSG00000182511), LCK (ENSG00000182866), SRC (ENSG00000197122), LYN (ENSG00000254087)

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Gallus gallus	P00523	100.0%	Diamond
Coturnix japonica	P34908	100.0%	Diamond
Drosophila melanogaster	Q08012	100.0%	Diamond
Bos taurus	A0JNB0	99.6%	Diamond
Sus scrofa	A1Y2K1	99.4%	Diamond
Pan troglodytes	P0C0K6	99.3%	Diamond
Felis catus	P14238	98.7%	Diamond
Xenopus laevis	P87379	98.7%	Diamond
Calliphora vicina	P11681	98.6%	Diamond
Macaca fascicularis	Q1KL86	98.0%	Diamond
Avian retrovirus IC10	P10533	100.0%	Diamond
Avian sarcoma virus PR2257	P15054	100.0%	Diamond
Rous-associated virus type 1	P27966	100.0%	Diamond
Avian sarcoma virus S2	P14085	99.8%	Diamond
Avian sarcoma virus S1	P14084	99.6%	Diamond
Feline sarcoma virus (STRAIN HARDY-ZUCKERMAN 2)	P10447	99.3%	Diamond
Gardner-Arnstein feline sarcoma virus	P00542	99.1%	Diamond
Snyder-Theilen feline sarcoma virus	P00543	99.1%	Diamond
Rous sarcoma virus (strain Schmidt-Ruppin A)	P00524	99.0%	Diamond
Avian sarcoma virus RASV1441	P00525	99.0%	Diamond
Rous sarcoma virus - Prague C	P00526	99.0%	Diamond
Rous sarcoma virus (strain H-19)	P25020	99.0%	Diamond
Rous sarcoma virus (strain Schmidt-Ruppin E)	P63185	99.0%	Diamond
Y73 sarcoma virus	P00527	98.9%	Diamond
Avian carcinoma Mill Hill virus 2	P00531	98.9%	Diamond
Murine sarcoma virus 3611	P00532	98.8%	Diamond
Abelson murine leukemia virus	P00521	98.7%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
ADCYAP1	protein-coding	116
ENOSF1	protein-coding	55556
TYMS	protein-coding	7298
CLUL1	protein-coding	27098
TYMSOS	ncRNA	494514
CETN1	protein-coding	1068
LINC01904	ncRNA	388456

Protein

Protein identifiers

Tyrosine-protein kinase Yes — P07947 (reviewed: P07947)

Alternative names: Proto-oncogene c-Yes, p61-Yes

All UniProt accessions (2): P07947, J3QRU1

UniProt curated annotations — full annotation on UniProt →

Function. Non-receptor protein tyrosine kinase that is involved in the regulation of cell growth and survival, apoptosis, cell-cell adhesion, cytoskeleton remodeling, and differentiation. Stimulation by receptor tyrosine kinases (RTKs) including EGFR, PDGFR, CSF1R and FGFR leads to recruitment of YES1 to the phosphorylated receptor, and activation and phosphorylation of downstream substrates. Upon EGFR activation, promotes the phosphorylation of PARD3 to favor epithelial tight junction assembly. Participates in the phosphorylation of specific junctional components such as CTNND1 by stimulating the FYN and FER tyrosine kinases at cell-cell contacts. Upon T-cell stimulation by CXCL12, phosphorylates collapsin response mediator protein 2/DPYSL2 and induces T-cell migration. Participates in CD95L/FASLG signaling pathway and mediates AKT-mediated cell migration. Plays a role in cell cycle progression by phosphorylating the cyclin-dependent kinase 4/CDK4 thus regulating the G1 phase. Also involved in G2/M progression and cytokinesis. Catalyzes phosphorylation of organic cation transporter OCT2 which induces its transport activity.

Subunit / interactions. Interacts with YAP1 and CSF1R. Interacts with CTNND1; this interaction allows YES1-mediated activation of FYN and FER and subsequent phosphorylation of CTNND1. Interacts with FASLG. Interacts with IL6ST/gp130. Interacts with SCRIB, when YES1 is in a closed conformation; the interaction facilitates YES1 autophosphorylation.

Subcellular location. Cell membrane. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Cytosol. Cell junction.

Tissue specificity. Expressed in the epithelial cells of renal proximal tubules and stomach as well as hematopoietic cells in the bone marrow and spleen in the fetal tissues. In adult, expressed in epithelial cells of the renal proximal tubules and present in keratinocytes in the basal epidermal layer of epidermis.

Post-translational modifications. Phosphorylated. Phosphorylation by CSK on the C-terminal tail maintains the enzyme in an inactive state. Autophosphorylation at Tyr-426 maintains enzyme activity by blocking CSK-mediated inhibition. Palmitoylation at Cys-3 promotes membrane localization.

Similarity. Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.

RefSeq proteins (1): NP_005424* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR000980	SH2	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR001452	SH3_domain	Domain
IPR008266	Tyr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR020635	Tyr_kinase_cat_dom	Domain
IPR035751	Yes_SH3	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR036860	SH2_dom_sf	Homologous_superfamily
IPR050198	Non-receptor_tyrosine_kinases	Family

Pfam: PF00017, PF00018, PF07714

Enzyme classification (BRENDA)

• EC 2.7.10.2 — non-specific protein-tyrosine kinase (BRENDA: 41 organisms, 396 substrates, 479 inhibitors, 43 Km, 32 kcat entries)

Substrate kinetics (BRENDA)

6 substrates with measured Km, best-characterized 6. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.014–17.64	12
[KDSRC KINASE]-L-TYROSINE	0.0057–0.24	12
POLY(GLU4-TYR)	0.018–0.659	10
EEEEYIQ[DP]-8-HYDROXY-5-(N,N-DIMETHYLSULFONAMIDO	0.057	1
S1 PEPTIDE	0.037	1
EEEEY	—	0

Catalyzed reactions (Rhea)

• L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (RHEA:10596)

UniProt features (30 total): modified residue 8, strand 5, domain 3, lipid moiety-binding region 2, sequence variant 2, binding site 2, initiator methionine 1, chain 1, mutagenesis site 1, turn 1, helix 1, region of interest 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
2HDA	Yes SH3 domain	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P07947-F1	83.19	0.67

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Kinases, Tyr protein kinases, Predicted intracellular proteins, Plasma proteins, FDA approved drug targets, Small molecule drugs

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; plasma membrane

Antibody reliability (HPA): IH approved · IF supported

Functional residue map

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

Catalytic / active sites (1)

Position	Role
396	proton acceptor

Ligand- & substrate-binding residues (2)

Position	Role
283–291	ATP
305	ATP

Post-translational modifications (10)

Type	Positions
Phosphothreonine	21
Phosphotyrosine	32, 336, 345, 426, 446, 537
Phosphoserine	40
N-myristoyl glycine	2
S-palmitoyl cysteine	3

Mutagenesis-validated functional residues (1)

Position	Phenotype
426	about 50% loss of csk-mediated inhibition.

Function

Pathways and Gene Ontology

Reactome pathways

10 curated (TAS) of 47; 13 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

47 pathways:

ID	Pathway	Evidence
R-HSA-9664323	FCGR3A-mediated IL10 synthesis ⚕	curated
R-HSA-9664422	FCGR3A-mediated phagocytosis ⚕	curated
R-HSA-9670439	Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants ⚕	curated
R-HSA-389513	Co-inhibition by CTLA4	curated
R-HSA-389356	Co-stimulation by CD28	curated
R-HSA-3928665	EPH-ephrin mediated repulsion of cells	curated
R-HSA-2029481	FCGR activation	curated
R-HSA-210990	PECAM1 interactions	curated
R-HSA-1433559	Regulation of KIT signaling	curated
R-HSA-1227986	Signaling by ERBB2	curated
R-HSA-9662851	Anti-inflammatory response favouring Leishmania parasite infection ⚕	—
R-HSA-1643685	Disease ⚕	—
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers ⚕	—
R-HSA-5663205	Infectious disease ⚕	—
R-HSA-9658195	Leishmania infection ⚕	—
R-HSA-9664433	Leishmania parasite growth and survival ⚕	—
R-HSA-9664417	Leishmania phagocytosis ⚕	—
R-HSA-9664407	Parasite infection ⚕	—
R-HSA-9824443	Parasitic Infection Pathways ⚕	—
R-HSA-9669938	Signaling by KIT in disease ⚕	—
R-HSA-1280218	Adaptive Immune System	—
R-HSA-422475	Axon guidance	—
R-HSA-202733	Cell surface interactions at the vascular wall	—
R-HSA-1280215	Cytokine Signaling in Immune system	—
R-HSA-1266738	Developmental Biology	—
R-HSA-2682334	EPH-Ephrin signaling	electronic
R-HSA-3928663	EPHA-mediated growth cone collapse	electronic
R-HSA-3928662	EPHB-mediated forward signaling	electronic
R-HSA-2029480	Fcgamma receptor (FCGR) dependent phagocytosis	—
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-212436	Generic Transcription Pathway	—
R-HSA-109582	Hemostasis	—
R-HSA-168256	Immune System	—
R-HSA-168249	Innate Immune System	—
R-HSA-512988	Interleukin-3, Interleukin-5 and GM-CSF signaling	—
R-HSA-9675108	Nervous system development	—
R-HSA-73857	RNA Polymerase II Transcription	—
R-HSA-8941326	RUNX2 regulates bone development	—
R-HSA-8940973	RUNX2 regulates osteoblast differentiation	electronic
R-HSA-388841	Regulation of T cell activation by CD28 family	—
R-HSA-912631	Regulation of signaling by CBL	electronic
R-HSA-162582	Signal Transduction	—
R-HSA-9680350	Signaling by CSF1 (M-CSF) in myeloid cells	electronic
R-HSA-449147	Signaling by Interleukins	—
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases	—
R-HSA-1433557	Signaling by SCF-KIT	electronic
R-HSA-8878166	Transcriptional regulation by RUNX2	—

MSigDB gene sets: 388 (showing top): GGGACCA_MIR133A_MIR133B, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_CARBOHYDRATE_TRANSPORT, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_INFLAMMATORY_RESPONSE_TO_ANTIGENIC_STIMULUS, DORSAM_HOXA9_TARGETS_UP, GOBP_CIRCULATORY_SYSTEM_PROCESS, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_CELLULAR_RESPONSE_TO_LIPID, TGCACTT_MIR519C_MIR519B_MIR519A, HOFMANN_CELL_LYMPHOMA_UP, PID_NETRIN_PATHWAY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN

GO Biological Process (12): negative regulation of inflammatory response to antigenic stimulus (GO:0002862), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), cell differentiation (GO:0030154), T cell costimulation (GO:0031295), protein modification process (GO:0036211), Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096), regulation of vascular permeability (GO:0043114), ephrin receptor signaling pathway (GO:0048013), leukocyte migration (GO:0050900), protein phosphorylation (GO:0006468), endocytosis (GO:0006897), actin cortical patch localization (GO:0051666)

GO Molecular Function (12): phosphotyrosine residue binding (GO:0001784), protein tyrosine kinase activity (GO:0004713), non-membrane spanning protein tyrosine kinase activity (GO:0004715), signaling receptor binding (GO:0005102), ATP binding (GO:0005524), enzyme binding (GO:0019899), transmembrane transporter binding (GO:0044325), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (8): Golgi apparatus (GO:0005794), centrosome (GO:0005813), cytosol (GO:0005829), actin filament (GO:0005884), plasma membrane (GO:0005886), focal adhesion (GO:0005925), extracellular exosome (GO:0070062), anchoring junction (GO:0070161)

Reactome top-level categories

14 top-level categories:

Category	Pathways
EPH-Ephrin signaling	3
Signaling by Receptor Tyrosine Kinases	2
Regulation of T cell activation by CD28 family	2
Signaling by SCF-KIT	1
Fcgamma receptor (FCGR) dependent phagocytosis	1
Cell surface interactions at the vascular wall	1
Axon guidance	1
RUNX2 regulates bone development	1
Interleukin-3, Interleukin-5 and GM-CSF signaling	1
Anti-inflammatory response favouring Leishmania parasite infection	1
Leishmania phagocytosis	1
Signaling by KIT in disease	1
Cytokine Signaling in Immune system	1
Immune System	1

GO top-level categories

53 GO namespaces:

Category	Terms
protein binding	3
cytoplasm	2
inflammatory response to antigenic stimulus	1
regulation of inflammatory response to antigenic stimulus	1
negative regulation of inflammatory response	1
negative regulation of immune response	1
enzyme-linked receptor protein signaling pathway	1
cellular developmental process	1
lymphocyte costimulation	1
positive regulation of T cell activation	1
protein metabolic process	1
macromolecule modification	1
Fc receptor mediated stimulatory signaling pathway	1
phagocytosis	1
Fc-gamma receptor signaling pathway	1
vascular process in circulatory system	1
blood circulation	1
regulation of biological quality	1
cell surface receptor protein tyrosine kinase signaling pathway	1
immune system process	1
cell migration	1
phosphorylation	1
protein modification process	1
vesicle budding from membrane	1
membrane invagination	1
import into cell	1
cellular localization	1
protein phosphorylated amino acid binding	1
protein kinase activity	1
protein tyrosine kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
endomembrane system	1
intracellular membrane-bounded organelle	1
centriole	1
microtubule organizing center	1
cellular anatomical structure	1
actin cytoskeleton	1
polymeric cytoskeletal fiber	1
membrane	1
cell periphery	1
cell-substrate junction	1
extracellular vesicle	1
cell junction	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 9 of 32 annotations. The rest are phylogenetic / computational / electronic (IEA).

9 experimentally-supported GO terms:

GO term	NS	Evidence
Golgi apparatus	CC	direct assay
cytosol	CC	direct assay
extracellular exosome	CC	high-throughput assay
focal adhesion	CC	high-throughput assay
plasma membrane	CC	direct assay
enzyme binding	MF	physical interaction
phosphotyrosine residue binding	MF	physical interaction
protein tyrosine kinase activity	MF	direct assay
transmembrane transporter binding	MF	physical interaction

Protein interactions and networks

STRING

showing 16 of 1,535 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
YES1	TYMS	P04818	744
YES1	ADRA2C	P18825	671
YES1	SMIM30	A4D0T7	533
YES1	YAP1	P46937	470
YES1	CENPA	P49450	435
YES1	ENOSF1	Q7L5Y1	389
YES1	MAL2	Q969L2	360
YES1	NCF1	P14598	359
YES1	CLUL1	Q15846	343
YES1	TP53	P04637	339
YES1	CD1D	P15813	332
YES1	CCND1	P24385	330
YES1	MTOR	P42345	326
YES1	PIK3CA	P42336	323
YES1	LAMB3	Q13751	323
YES1	CTNNB1	P35222	323

IntAct

Human interaction partners of YES1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 113 partners by confidence:

Partner	Interaction type	MIscore	Records
CDC37	physical association	0.740	1
PTK2	physical association	0.720	7
FXR2	physical association	0.720	6
SOCS3	physical association	0.720	6
SSBP3	physical association	0.720	6
THAP1	physical association	0.720	6
TRAF2	physical association	0.720	6
TRAF6	physical association	0.720	6
ZBTB8A	physical association	0.720	6
FUNDC1	physical association	0.670	4
OLIG1	physical association	0.570	3
EFS	physical association	0.560	5
IKZF3	physical association	0.560	5
AMOTL2	physical association	0.560	3
BCAR1	physical association	0.560	3
BICD2	physical association	0.560	3
C1orf94	physical association	0.560	3
CARD9	physical association	0.560	3
CBLB	physical association	0.560	3
CBLC	physical association	0.560	3
CEP57L1	physical association	0.560	3
CEP83	physical association	0.560	3
CHMP1A	physical association	0.560	3
CPSF6	physical association	0.560	3
CRKL	physical association	0.560	3
CYSRT1	physical association	0.560	3
DDIT4L	physical association	0.560	3
DENND2C	physical association	0.560	3
DES	physical association	0.560	3
DOK2	physical association	0.560	3

BioGRID (516 interactions; top human partners by supporting records): CDC37 (Affinity Capture-MS; 4 records), FGFR1 (Affinity Capture-Western; 4 records), FGR (Affinity Capture-MS; 4 records), FYN (Affinity Capture-MS; 4 records), KHDRBS1 (Protein-peptide; 4 records), KRAS (Affinity Capture-MS; 4 records), PTK2 (Two-hybrid; 4 records), ANLN (Affinity Capture-MS; 3 records), CTNND1 (Affinity Capture-Western; 3 records), EZH2 (Affinity Capture-MS; 3 records), HOXB5 (Affinity Capture-MS; 3 records), HSP90AB3P (Affinity Capture-MS; 3 records), LCK (Affinity Capture-MS; 3 records), LYN (Proximity Label-MS; 3 records), OCLN (Affinity Capture-Western; 3 records)

SIGNOR signaling

showing 15 of 18 signaling interactions:

A	Effect	B	Mechanism
YES1	down-regulates	CDK4	phosphorylation
YES1	“up-regulates activity”	YES1	phosphorylation
YES1	“up-regulates activity”	WBP2	phosphorylation
YES1	“down-regulates activity”	YY1	phosphorylation
YES1	“up-regulates quantity by stabilization”	SOCS1	phosphorylation
AXL	“up-regulates activity”	YES1	phosphorylation
EPHA2	“up-regulates activity”	YES1	phosphorylation
YES1	“up-regulates activity”	YAP1	phosphorylation
YES1	“up-regulates activity”	WWTR1	phosphorylation
IL6ST	“up-regulates activity”	YES1	phosphorylation
YES1	“up-regulates activity”	ANXA2	phosphorylation
YES1	“up-regulates activity”	POU2F2	phosphorylation
RPL10	down-regulates	YES1	binding
YES1	“up-regulates activity”	GLO1	phosphorylation
YES1	“down-regulates activity”	SOCS1	phosphorylation

Protein complexes (CORUM) (7)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

7 complexes by size:

Complex	Subunits	Members
★ CTNNB1-TBX5-YAP1-YES1 complex	4	YAP1, YES1, CTNNB1, TBX5
★ FYN-LYN-RASA1-YES1 complex	4	FYN, LYN, RASA1, YES1
★ SMIM30-YES1 complex	2	SMIM30, YES1
★ SCRIB-YES1 complex	2	SCRIB, YES1
★ FLT1-YES complex	2	FLT1, YES1
★ CD36-YES1 complex	2	CD36, YES1
★ PDGFRB-YES1 complex	2	PDGFRB, YES1

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 113 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 PTK6	6	41.8×	1e-06
Signaling by Non-Receptor Tyrosine Kinases	6	41.8×	1e-06
RIPK1-mediated regulated necrosis	5	29.3×	7e-05
Extra-nuclear estrogen signaling	6	13.1×	4e-04
Constitutive Signaling by Aberrant PI3K in Cancer	8	13.0×	3e-05
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	9	11.2×	2e-05
VEGFA-VEGFR2 Pathway	6	10.7×	1e-03
PIP3 activates AKT signaling	10	8.6×	3e-05

GO biological processes:

GO term	Partners	Fold	FDR
vascular endothelial growth factor receptor signaling pathway	5	23.4×	6e-04
epidermal growth factor receptor signaling pathway	7	16.8×	1e-04
cell surface receptor protein tyrosine kinase signaling pathway	9	15.2×	9e-06
epithelial cell proliferation	5	15.2×	2e-03
protein K63-linked ubiquitination	5	13.0×	3e-03
insulin receptor signaling pathway	5	10.8×	6e-03
male gonad development	6	9.1×	4e-03
cytokine-mediated signaling pathway	7	8.9×	2e-03

Disease & clinical

Genetic variants

Variant evidence for YES1: 75 ClinVar records (0 pathogenic / likely pathogenic); 13 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	58
Likely benign	3
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 33 predictions of 1,274):

Position(s)	Effect	Δscore	Sites
18:736806–736807	donor_loss	1.0000	4
18:736962–736963	acceptor_loss	1.0000	2
18:736963	acceptor_gain	1.0000
18:739733–739734	donor_loss	1.0000	6
18:739812–739813	acceptor_loss	1.0000	6
18:739835	acceptor_gain	1.0000
18:742917	donor_loss	1.0000
18:743098–743099	acceptor_loss	1.0000	5
18:756837	acceptor_loss	1.0000	2
18:724633–724634	acceptor_loss	0.9900	5

AlphaMissense

2,264 missense substitutions predicted likely pathogenic (of 3,527 scored), across 432 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M384	9	0.994	1.000
M324	9	0.984	1.000
M312	9	0.976	0.998
M476	9	0.957	0.999
M491	9	0.956	1.000
M351	9	0.921	0.995
M505	9	0.909	0.991
M390	9	0.797	0.976
H394	8	1.000	1.000
D396	8	1.000	1.000
N401	8	1.000	1.000
D414	8	1.000	1.000
D454	8	1.000	1.000
H211	8	0.999	1.000
F415	8	0.999	1.000
F434	8	0.999	1.000
F288	8	0.998	1.000
F317	8	0.998	1.000
F449	8	0.997	1.000
F519	8	0.997	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	5.57e-06
Kidney Chromophobe (TCGA)	unfavorable	2.71e-05
Pancreatic Adenocarcinoma (TCGA)	unfavorable	0.000208

Disease associations

OMIM: gene MIM:164880 | disease phenotypes:

GWAS associations

13 associations:

Study	Trait	p-value
GCST006624_106	Systolic blood pressure	2e-21
GCST007267_200	Systolic blood pressure	6e-16
GCST006010_17	Mean arterial pressure	3e-12
GCST007703_54	Systolic blood pressure	3e-11
GCST007706_39	Mean arterial pressure	4e-11
GCST005979_4	Systolic blood pressure	5e-11
GCST005978_3	Diastolic blood pressure	7e-10
GCST007704_29	Diastolic blood pressure	1e-8
GCST009888_1	Thyroid autoantibody positivity (anti-thyroglobulin (TgAb) and/or anti-thyroid peroxidase (TPOAb) levels)	2e-8
GCST002279_94	PR interval in Tripanosoma cruzi seropositivity	3e-7
GCST007707_1	Hypertension	7e-7
GCST001918_3	Pulmonary function in asthmatics	4e-6
GCST005024_33	Pursuit maintenance gain	6e-6

EFO canonical traits (from GWAS)

6 canonical traits:

EFO ID	Trait name
EFO:0003892	pulmonary function measurement
EFO:0004462	PR interval
EFO:0008433	pursuit maintenance gain measurement
EFO:0006336	diastolic blood pressure
EFO:0006335	systolic blood pressure
EFO:0006340	mean arterial pressure

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2073 (SINGLE PROTEIN), CHEMBL2363074 (PROTEIN FAMILY), CHEMBL4523728 (PROTEIN-PROTEIN INTERACTION)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the YES1 protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

1 curated-mechanism drugs:

Drug	Modality	Max phase
JNJ-26483327	Small molecule	1

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes YES1 — the drug acts on the assembly or class, not necessarily on this subunit alone.

5 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
DASATINIB ANHYDROUS	SRC	10	4
ENMD-981693	SRC	10	2
ILORASERTIB	SRC	10	2
TG100-801	SRC	10	2
XL-228	SRC	10	1

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 343,539 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

showing 60 of 66 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1289926	AXITINIB	4	16,510
CHEMBL288441	BOSUTINIB	4	12,869
CHEMBL3545311	BRIGATINIB	4	5,988
CHEMBL601719	CRIZOTINIB	4	15,133
CHEMBL2028663	DABRAFENIB	4	13,060
CHEMBL5416410	DASATINIB	4	674
CHEMBL1421	DASATINIB ANHYDROUS	4	55,947
CHEMBL553	ERLOTINIB	4	109,860
CHEMBL1287853	FEDRATINIB	4	3,770
CHEMBL3301622	GILTERITINIB	4	2,542
CHEMBL1873475	IBRUTINIB	4	8,363
CHEMBL1852688	INFIGRATINIB	4	2,298
CHEMBL1834657	INFIGRATINIB PHOSPHATE	4	330
CHEMBL608533	MIDOSTAURIN	4	7,641
CHEMBL180022	NERATINIB	4	9,891
CHEMBL255863	NILOTINIB	4	39,362
CHEMBL502835	NINTEDANIB	4	8,978
CHEMBL477772	PAZOPANIB	4	16,241
CHEMBL1171837	PONATINIB	4	9,435
CHEMBL576982	QUIZARTINIB	4	4,647
CHEMBL535	SUNITINIB	4
CHEMBL24828	VANDETANIB	4
CHEMBL31965	CANERTINIB	3
CHEMBL491473	CEDIRANIB	3
CHEMBL522892	DOVITINIB	3
CHEMBL603469	LESTAURTINIB	3
CHEMBL1908391	MASITINIB	3
CHEMBL572881	MOTESANIB	3
CHEMBL50	QUERCETIN	3
CHEMBL217092	SARACATINIB	3
CHEMBL3544983	TESEVATINIB	3
CHEMBL587723	AEE-788	2
CHEMBL495727	AT-9283	2
CHEMBL8260	BAICALEIN	2
CHEMBL3545396	BMS-690514	2
CHEMBL402548	DANUSERTIB	2
CHEMBL215152	DEFOSBARASERTIB	2
CHEMBL103667	DORAMAPIMOD	2
CHEMBL482968	ENMD-2076	2
CHEMBL1230609	FORETINIB	2
CHEMBL151	LUTEOLIN	2
CHEMBL564829	MILCICLIB	2
CHEMBL119385	NEFLAMAPIMOD	2
CHEMBL253969	OSI-632	2
CHEMBL607707	PELITINIB	2
CHEMBL475251	R-406	2
CHEMBL558752	RAF-265	2
CHEMBL1738757	REBASTINIB	2
CHEMBL1721885	SU-014813	2
CHEMBL403989	TG100-801	2
CHEMBL572878	TOZASERTIB	2
CHEMBL2103842	VARLITINIB	2
CHEMBL551064	AEW-541	1
CHEMBL3545360	ASP-3026	1
CHEMBL574738	AST-487	1
CHEMBL4439321	ATUVECICLIB	1
CHEMBL2138625	AV-412 FREE BASE	1
CHEMBL2041933	AZD-7762	1
CHEMBL150	KAEMPFEROL	1
CHEMBL1908397	KW-2449	1

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Src family

Most potent curated ligand interactions (9 total), top 9:

Ligand	Action	Affinity	Parameter
eCF506	Inhibition	9.3	pIC50
rebastinib	Inhibition	8.82	pIC50
saracatinib	Inhibition	8.4	pIC50
ibrutinib	Inhibition	8.39	pIC50
nemtabrutinib	Inhibition	8.38	pIC50
nefextinib	Inhibition	8.24	pIC50
SU6656	Inhibition	7.7	pIC50
xiliertinib	Inhibition	6.48	pIC50
spebrutinib	Inhibition	6.14	pIC50

Binding affinities (BindingDB)

190 measured of 306 human assays (313 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL3808884	EC50	0.04 nM
3-[2-(Imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide	EC50	0.05 nM
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
AP-26113	IC50	0.37 nM
1-[(2R)-2-[4-amino-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]prop-2-en-1-one	IC50	0.8 nM	US-20240317756: INHIBITORS OF BRUTON’S TYROSINE KINASE
CHEMBL457614	IC50	0.93 nM
N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methylthieno[3,2-d]pyrimidin-4-yl)amino]-1,4-dihydropyrrolo[3,4-d]pyrazole-5-carboxamide	IC50	1 nM	US-8530652: Pyrrolopyrazoles, potent kinase inhibitors
4-Methyl-3-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)-N-(3-(trifluoromethyl)phenyl)benzamide	IC50	1 nM
N-[4-[4-amino-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]cyclohexyl]prop-2-enamide	IC50	1.1 nM	US-9181263: Inhibitors of bruton’s tyrosine kinase
[4-[[7-(2-chloro-5-hydroxyphenyl)-5-methyl-1,2,4-benzotriazin-3-yl]amino]phenyl]-piperazin-1-ylmethanone	IC50	1.2 nM	US-8481536: Benzotriazine inhibitors of kinases
rac-2-(6-hydroxy-6-methylheptan-2-ylamino)-4-methyl-6-(5-methyl-1H-pyrazol-3-ylamino)nicotinonitrile hydrochloride	KI	1.2 nM
4-chloro-3-(5-methyl-3-(4-(3-(pyrrolidin-1-yl)propyl)phenylamino)benzo[e][1,2,4]triazin-7-yl)phenol	IC50	1.5 nM
CHEMBL5268244	IC50	1.6 nM
Staurosporine	KD	1.7 nM
CHEMBL5415503	IC50	2.1 nM
CHEMBL5280844	IC50	2.5 nM
N-[3-(diethylaminomethoxy)phenyl]-7-(2,6-dimethylphenyl)-5-methyl-1,2,4-benzotriazin-3-amine	IC50	2.6 nM	US-8481536: Benzotriazine inhibitors of kinases
4-chloro-3-[5-methyl-3-(4-piperidin-4-ylsulfonylanilino)-1,2,4-benzotriazin-7-yl]phenol	IC50	2.8 nM	US-8481536: Benzotriazine inhibitors of kinases
N-(2-chloro-6-methylphenyl)-2-[4-(4-methylpiperazin-1-yl)anilino]-4-[2-(propanoylamino)anilino]pyrimidine-5-carboxamide	IC50	3 nM	US-12365664: Small molecule inhibitors of SRC tyrosine kinase
CEP-701	KD	3.4 nM
CHEMBL3893914	KI	4 nM
N-(2-chloro-6-methylphenyl)-2-[3-methyl-4-(4-methylpiperazin-1-yl)anilino]-4-[2-(prop-2-enoylamino)anilino]pyrimidine-5-carboxamide	IC50	4 nM	US-12365664: Small molecule inhibitors of SRC tyrosine kinase
3-[[7-(2-chloro-5-hydroxyphenyl)-5-methyl-1,2,4-benzotriazin-3-yl]amino]-N-[2-(dimethylamino)ethyl]benzamide	IC50	5.3 nM	US-8481536: Benzotriazine inhibitors of kinases
4-[4-[(5-tert-butyl-2-quinolin-6-ylpyrazol-3-yl)carbamoylamino]-3-fluorophenoxy]-N-methylpyridine-2-carboxamide	IC50	5.5 nM
N-[2-[[5-cyclopropyl-2-[4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]phenyl]prop-2-enamide	IC50	5.5 nM	US-12365664: Small molecule inhibitors of SRC tyrosine kinase
N-[2-[[5-ethyl-2-[4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]phenyl]prop-2-enamide	IC50	5.5 nM	US-12365664: Small molecule inhibitors of SRC tyrosine kinase
N-[2-[[5-bromo-2-[4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]phenyl]prop-2-enamide	IC50	5.5 nM	US-12365664: Small molecule inhibitors of SRC tyrosine kinase
N-[2-[[5-methyl-2-[4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]phenyl]prop-2-enamide	IC50	5.5 nM	US-12365664: Small molecule inhibitors of SRC tyrosine kinase
N-[2-[[5-iodo-2-[4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]phenyl]prop-2-enamide	IC50	5.5 nM	US-12365664: Small molecule inhibitors of SRC tyrosine kinase
N-[2-[[2-[4-(4-methylpiperazin-1-yl)anilino]thieno[3,2-d]pyrimidin-4-yl]amino]phenyl]prop-2-enamide	IC50	5.5 nM	US-12365664: Small molecule inhibitors of SRC tyrosine kinase
N-(2,6-dichlorophenyl)-2-[4-(4-methylpiperazin-1-yl)anilino]-4-[2-(prop-2-enoylamino)anilino]pyrimidine-5-carboxamide	IC50	5.5 nM	US-12365664: Small molecule inhibitors of SRC tyrosine kinase
N-(2,6-dimethylphenyl)-2-[4-(4-methylpiperazin-1-yl)anilino]-4-[2-(prop-2-enoylamino)anilino]pyrimidine-5-carboxamide	IC50	5.5 nM	US-12365664: Small molecule inhibitors of SRC tyrosine kinase
N-[2-[[5-chloro-2-[4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]-5-methylphenyl]prop-2-enamide	IC50	5.5 nM	US-12365664: Small molecule inhibitors of SRC tyrosine kinase
N-[2-[[5-chloro-2-[4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]-6-methylphenyl]prop-2-enamide	IC50	5.5 nM	US-12365664: Small molecule inhibitors of SRC tyrosine kinase
N-[2-[[5-chloro-2-[4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]-3-fluorophenyl]prop-2-enamide	IC50	5.5 nM	US-12365664: Small molecule inhibitors of SRC tyrosine kinase
N-(2-chloro-6-methylphenyl)-4-[5-fluoro-2-(prop-2-enoylamino)anilino]-2-[4-(4-methylpiperazin-1-yl)anilino]pyrimidine-5-carboxamide	IC50	5.5 nM	US-12365664: Small molecule inhibitors of SRC tyrosine kinase
N-(2-chloro-6-methylphenyl)-4-[2-fluoro-6-(prop-2-enoylamino)anilino]-2-[4-(4-methylpiperazin-1-yl)anilino]pyrimidine-5-carboxamide	IC50	5.5 nM	US-12365664: Small molecule inhibitors of SRC tyrosine kinase
3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	IC50	5.6 nM	US-8822500: Tyrosine kinase inhibitors
4-[3-[(6R,8aS)-1,1-dimethyl-3-oxo-6,7,8,8a-tetrahydro-5H-[1,3]oxazolo[3,4-a]pyridin-6-yl]-8-aminoimidazo[1,5-a]pyrazin-1-yl]-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	IC50	5.6 nM	US-9481682: Substituted benzamides and substituted pyridinecarboxamides as Btk inhibitors
4-chloro-3-[6-methyl-3-[4-(2-pyrrolidin-1-ylethoxy)anilino]-1,2,4-benzotriazin-7-yl]phenol	IC50	5.7 nM	US-8481536: Benzotriazine inhibitors of kinases
7-(2,6-dimethylphenyl)-5-methyl-N-[3-(2-pyrrolidin-1-ylethoxy)phenyl]-1,2,4-benzotriazin-3-amine	IC50	6 nM	US-8481536: Benzotriazine inhibitors of kinases
Staurosporine, 8	IC50	6.5 nM
CHEMBL3923175	IC50	7 nM
CHEMBL1952141	IC50	7 nM
TG-100855	KI	7.27 nM
Momelotinib	IC50	8 nM	US-9469613: (N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide
CHEMBL4465866	KD	8 nM
CHEMBL4576489	KD	8 nM
ASP-3026	IC50	10 nM
4-[8-amino-3-[(6R,8aS)-3-oxo-2,5,6,7,8,8a-hexahydro-1H-indolizin-6-yl]imidazo[1,5-a]pyrazin-1-yl]-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	IC50	11 nM	US-9481682: Substituted benzamides and substituted pyridinecarboxamides as Btk inhibitors

ChEMBL bioactivities

314 potent at pChembl≥5 of 333 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.52	IC50	0.3	nM	CHEMBL400402
9.52	Kd	0.3	nM	DASATINIB
9.41	IC50	0.39	nM	CHEMBL5280844
9.40	IC50	0.4	nM	BOSUTINIB
9.30	IC50	0.5	nM	DASATINIB
9.30	IC50	0.5	nM	CHEMBL400402
9.30	IC50	0.5	nM	CHEMBL364623
9.15	IC50	0.7	nM	SARACATINIB
9.15	IC50	0.7	nM	CHEMBL3651257
9.10	IC50	0.8	nM	CHEMBL3426225
9.10	IC50	0.8	nM	CHEMBL3647967
9.05	IC50	0.89	nM	PONATINIB
9.00	Kd	1	nM	CHEMBL400402
9.00	IC50	1	nM	CHEMBL436137
9.00	IC50	1	nM	AT-9283
9.00	IC50	1	nM	CHEMBL4798527
9.00	Kd	1	nM	CHEMBL249097
8.92	IC50	1.2	nM	CHEMBL3651296
8.92	IC50	1.2	nM	CHEMBL436137
8.91	IC50	1.24	nM	CHEMBL3651228
8.89	IC50	1.28	nM	CHEMBL249821
8.89	IC50	1.3	nM	CHEMBL249821
8.89	IC50	1.3	nM	CHEMBL5268244
8.85	IC50	1.4	nM	DOVITINIB
8.82	IC50	1.5	nM	REBASTINIB
8.77	IC50	1.7	nM	STAUROSPORINE
8.70	IC50	2	nM	CHEMBL364623
8.70	IC50	2	nM	CHEMBL3426233
8.68	IC50	2.1	nM	CHEMBL2336005
8.64	IC50	2.3	nM	CHEMBL5280361
8.64	Kd	2.3	nM	CHEMBL386051
8.63	IC50	2.35	nM	STAUROSPORINE
8.62	IC50	2.39	nM	STAUROSPORINE
8.60	IC50	2.5	nM	REBASTINIB
8.59	IC50	2.6	nM	CHEMBL3651297
8.59	IC50	2.6	nM	CHEMBL218102
8.59	IC50	2.56	nM	STAUROSPORINE
8.52	IC50	3	nM	CHEMBL457614
8.52	IC50	3	nM	CHEMBL217090
8.51	IC50	3.1	nM	CHEMBL231218
8.43	IC50	3.7	nM	CHEMBL218549
8.43	Kd	3.715	nM	DASATINIB ANHYDROUS
8.40	IC50	4	nM	CHEMBL3923175
8.40	IC50	4	nM	SARACATINIB
8.40	Kd	4	nM	DASATINIB
8.40	Kd	4	nM	DASATINIB ANHYDROUS
8.40	Kd	4	nM	BOSUTINIB
8.39	IC50	4.1	nM	CHEMBL250625
8.39	IC50	4.1	nM	IBRUTINIB
8.36	IC50	4.4	nM	STAUROSPORINE

PubChem BioAssay actives

252 with measured affinity, of 2313 total; 50 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
N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide;hydrate	435328: Binding constant for YES kinase domain	kd	0.0003	uM
4-chloro-3-[5-methyl-3-[4-(2-pyrrolidin-1-ylethoxy)anilino]-1,2,4-benzotriazin-7-yl]phenol	325210: Inhibition of YES	ic50	0.0003	uM
(2-chloro-4-phenoxyphenyl)-[4-[[(6S)-6-(hydroxymethyl)oxan-3-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-5-yl]methanone	1939138: Inhibition of YES (unknown origin)	ic50	0.0004	uM
Bosutinib	507428: Inhibition of YES1	ic50	0.0004	uM
N-(2-chloro-6-methylphenyl)-2-[(2,6-dimethylpyrimidin-4-yl)amino]-1,3-thiazole-5-carboxamide	2206135: Inhibition of YES1 (unknown origin)	ic50	0.0005	uM
tert-butyl N-[4-[4-amino-1-[2-[4-(dimethylamino)piperidin-1-yl]ethyl]pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl]carbamate	1310132: Inhibition of human YES using poly[Glu,Tyr]4:1 as substrate in presence of [gamma-33P] ATP	ic50	0.0005	uM
N-(5-chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-(oxan-4-yloxy)quinazolin-4-amine	761477: Inhibition of Yes1 (unknown origin) by [gamma-33P]-ATP radiolabeled enzyme activity assay	ic50	0.0007	uM
3-[2-(4-amino-1-ethylpyrazolo[3,4-d]pyrimidin-3-yl)ethynyl]-4-methyl-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]benzamide	1206221: Inhibition of human Yes	ic50	0.0008	uM
Ponatinib	1716395: Binding affinity to human YES using poly[Glu:Tyr] (4:1) as substrate by radiometric hotspot kinase assay	ic50	0.0009	uM
7-(2,6-dimethylphenyl)-5-methyl-N-[4-(2-pyrrolidin-1-ylethoxy)phenyl]-1,2,4-benzotriazin-3-amine	276183: Inhibition of Yes	ic50	0.0010	uM
N-[3-[2-[4-amino-1-(4-hydroxycyclohexyl)pyrazolo[3,4-d]pyrimidin-3-yl]ethynyl]-4-methylphenyl]-4-methyl-3-(trifluoromethyl)benzamide	1734743: Inhibition of human full length recombinant YES using poly(Glu,Tyr)4:1 as substrate incubated for 40 mins in presence of [gamma33P-ATP] by radiometric scintillation counting analysis	ic50	0.0010	uM
1-cyclopropyl-3-[5-[6-(morpholin-4-ylmethyl)-1H-benzimidazol-2-yl]-1H-pyrazol-4-yl]urea	412621: Inhibition of Yes	ic50	0.0010	uM
3-[[4-(5-hydroxy-2-methylanilino)pyrimidin-2-yl]amino]benzamide	389065: Binding affinity to human YES	kd	0.0010	uM
4-[[7-(2-chloro-5-hydroxyphenyl)-5-methyl-1,2,4-benzotriazin-3-yl]amino]-N-(2-pyrrolidin-1-ylethyl)benzenesulfonamide	325210: Inhibition of YES	ic50	0.0013	uM
[(2S,3R,4R,5R)-5-[4-amino-3-(4-methylphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]-3-methyl-4-prop-2-ynoxyoxolan-2-yl]methyl 4-fluorosulfonylbenzoate	1940020: Inhibition of YES (unknown origin)	ic50	0.0013	uM
4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one	761477: Inhibition of Yes1 (unknown origin) by [gamma-33P]-ATP radiolabeled enzyme activity assay	ic50	0.0014	uM
4-[4-[(3-tert-butyl-1-quinolin-6-ylpyrazol-5-yl)carbamoylamino]-3-fluorophenoxy]-N-methylpyridine-2-carboxamide	761477: Inhibition of Yes1 (unknown origin) by [gamma-33P]-ATP radiolabeled enzyme activity assay	ic50	0.0015	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	2198460: Inhibition of human YES using poly[Glu:Tyr] (4:1) as substrate preincubated for 20 mins followed by [gamma-33P]-ATP addition and measured after 120 mins by radiometric Hot-SpotSM Kinase assay	ic50	0.0017	uM
[(2S,3R,4R,5R)-5-[4-amino-3-(4-methylphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]-3-methyl-4-prop-2-ynoxyoxolan-2-yl]methyl ethenesulfonate	1940020: Inhibition of YES (unknown origin)	ic50	0.0023	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	625018: Binding constant for YES kinase domain	kd	0.0023	uM
N-(5-chloro-1,3-benzodioxol-4-yl)-5-(oxan-4-yloxy)-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-amine	272224: Inhibition of recombinant C-YES by ELISA	ic50	0.0030	uM
5-chloro-2-N-[(1S)-1-(5-fluoro-2-pyridinyl)ethyl]-4-N-(3-propan-2-yloxy-1H-pyrazol-5-yl)pyrimidine-2,4-diamine	761477: Inhibition of Yes1 (unknown origin) by [gamma-33P]-ATP radiolabeled enzyme activity assay	ic50	0.0030	uM
Dasatinib	2149796: Binding affinity to human YES1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0037	uM
2-[[N-[2-[3-ethylsulfonyl-4-(4-methylpiperazin-1-yl)anilino]-5-fluoropyrimidin-4-yl]-5-(hydroxymethyl)-2-methylanilino]methyl]benzonitrile	1326072: Inhibition of N-terminal 6His-tagged full length recombinant human YES expressed in baculovirus expression system	ic50	0.0040	uM
4-chloro-3-[5-methyl-3-(4-piperidin-4-ylsulfonylanilino)-1,2,4-benzotriazin-7-yl]phenol	325210: Inhibition of YES	ic50	0.0041	uM
Ibrutinib	2188603: Inhibition of recombinant YES1 (unknown origin) preincubated for 1 hr in presence of ATP by Z-Lyte assay	ic50	0.0041	uM
4-chloro-3-[5-methyl-3-[4-(3-pyrrolidin-1-ylpropyl)anilino]-1,2,4-benzotriazin-7-yl]phenol	325210: Inhibition of YES	ic50	0.0048	uM
6-amino-7-(4-phenoxyphenyl)-9-[(3S)-1-prop-2-enoylpiperidin-3-yl]purin-8-one	1425212: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0050	uM
[4-[[7-(2-chloro-5-hydroxyphenyl)-5-methyl-1,2,4-benzotriazin-3-yl]amino]phenyl]-piperazin-1-ylmethanone	325210: Inhibition of YES	ic50	0.0052	uM
7-(2,6-dichlorophenyl)-5-methyl-N-[4-[2-(1-oxidopyrrolidin-1-ium-1-yl)ethoxy]phenyl]-1,2,4-benzotriazin-3-amine	330573: Inhibition of Yes by luminescence based kinase assay	ki	0.0060	uM
4-methyl-3-[[3-[2-(methylamino)pyrimidin-4-yl]-2-pyridinyl]oxy]-N-[3-(trifluoromethyl)phenyl]benzamide	761478: Inhibition of Yes1 (unknown origin) assessed as kinase-dependent enzymatic production of ADP from ATP using coupled luminescence-based reaction by ADP-Glo kinase assay	ic50	0.0087	uM
(3Z)-3-[[3-[3-(dimethylamino)propyl]-4,5,6,7-tetrahydro-1H-indol-2-yl]methylidene]-N-methyl-2-oxo-1H-indole-5-sulfonamide	220258: Inhibitory activity against Yes tyrosine kinase	ic50	0.0100	uM
3-[2-[(Z)-[5-(methylsulfamoyl)-2-oxo-1H-indol-3-ylidene]methyl]-4,5,6,7-tetrahydro-1H-indol-3-yl]propanamide	220258: Inhibitory activity against Yes tyrosine kinase	ic50	0.0100	uM
2-[4-[3-[2-[(Z)-[5-(methylsulfamoyl)-2-oxo-1H-indol-3-ylidene]methyl]-4,5,6,7-tetrahydro-1H-indol-3-yl]propyl]piperazin-1-yl]acetic acid	220258: Inhibitory activity against Yes tyrosine kinase	ic50	0.0100	uM
7-(2,6-dichlorophenyl)-5-methyl-N-[4-(2-pyrrolidin-1-ylethoxy)phenyl]-1,2,4-benzotriazin-3-amine	325210: Inhibition of YES	ic50	0.0100	uM
2-[4-[3-[2-[(Z)-(5-ethylsulfonyl-2-oxo-1H-indol-3-ylidene)methyl]-4,5,6,7-tetrahydro-1H-indol-3-yl]propyl]piperazin-1-yl]acetic acid	220258: Inhibitory activity against Yes tyrosine kinase	ic50	0.0100	uM
(3Z)-3-[[3-[3-(4-hydroxypiperidin-1-yl)propyl]-4,5,6,7-tetrahydro-1H-indol-2-yl]methylidene]-N-methyl-2-oxo-1H-indole-5-sulfonamide	220258: Inhibitory activity against Yes tyrosine kinase	ic50	0.0100	uM
(3Z)-N-methyl-3-[[3-[3-(4-methylpiperazin-1-yl)propyl]-4,5,6,7-tetrahydro-1H-indol-2-yl]methylidene]-2-oxo-1H-indole-5-sulfonamide	220258: Inhibitory activity against Yes tyrosine kinase	ic50	0.0100	uM
(3Z)-3-[[3-[3-[4-(2-hydroxyethyl)piperazin-1-yl]propyl]-4,5,6,7-tetrahydro-1H-indol-2-yl]methylidene]-N-methyl-2-oxo-1H-indole-5-sulfonamide	220258: Inhibitory activity against Yes tyrosine kinase	ic50	0.0100	uM
1-[2-[4-[(dimethylamino)methyl]piperidin-1-yl]ethyl]-3-(1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[3,4-d]pyrimidin-4-amine	1310132: Inhibition of human YES using poly[Glu,Tyr]4:1 as substrate in presence of [gamma-33P] ATP	ic50	0.0120	uM
4-[8-amino-3-[(6R,8aS)-3-oxo-2,5,6,7,8,8a-hexahydro-1H-indolizin-6-yl]imidazo[1,5-a]pyrazin-1-yl]-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1721761: Inhibition of YES1 (unknown origin)	ic50	0.0120	uM
6-[4-[(4-ethylpiperazin-1-yl)methyl]phenyl]-N-[(1R)-1-phenylethyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine	761477: Inhibition of Yes1 (unknown origin) by [gamma-33P]-ATP radiolabeled enzyme activity assay	ic50	0.0131	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	625018: Binding constant for YES kinase domain	kd	0.0180	uM
Brigatinib	2182804: Inhibition of human YES1 using poly (Glu, Tyr)4:1 as substrate in presence of [gamma33P]-ATP by HotSpot assay	ic50	0.0190	uM
3-chloro-4-[3-(5-chloro-1,3-dioxopyrido[1,2-c]pyrimidin-2-yl)-2-methylphenyl]-7-(2-hydroxypropan-2-yl)-9H-carbazole-1-carboxamide	1678397: Inhibition of YES1 (unknown origin)	ic50	0.0190	uM
ethyl 2-[4-[3-[2-[(Z)-[5-(methylsulfamoyl)-2-oxo-1H-indol-3-ylidene]methyl]-4,5,6,7-tetrahydro-1H-indol-3-yl]propyl]piperazin-1-yl]acetate	220258: Inhibitory activity against Yes tyrosine kinase	ic50	0.0200	uM
(3Z)-5-ethylsulfonyl-3-[[3-[3-(4-hydroxypiperidin-1-yl)propyl]-4,5,6,7-tetrahydro-1H-indol-2-yl]methylidene]-1H-indol-2-one	220258: Inhibitory activity against Yes tyrosine kinase	ic50	0.0200	uM
(3Z)-N,N-dimethyl-2-oxo-3-(4,5,6,7-tetrahydro-1H-indol-2-ylmethylidene)-1H-indole-5-sulfonamide	325713: Inhibition of Yes kinase	ic50	0.0200	uM
(3Z)-3-[[3-[3-(dimethylamino)propyl]-4,5,6,7-tetrahydro-1H-indol-2-yl]methylidene]-5-ethylsulfonyl-1H-indol-2-one	220258: Inhibitory activity against Yes tyrosine kinase	ic50	0.0200	uM
4-[8-amino-3-[(3R,6S)-1-(cyclopropanecarbonyl)-6-methylpiperidin-3-yl]imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1711668: Inhibition of human YES1	ic50	0.0210	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	2
sodium arsenite	increases abundance, increases expression	2
Air Pollutants	increases oxidation, increases expression, affects cotreatment, increases abundance	2
Arsenic	increases expression, affects methylation, increases abundance	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Ozone	increases oxidation, increases abundance, increases expression, affects cotreatment	2
Tobacco Smoke Pollution	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
bisphenol F	increases expression	1
2,4,6-tribromophenol	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
decabromobiphenyl ether	increases expression	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
cobaltous chloride	increases expression, increases secretion, decreases reaction, increases phosphorylation	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
benzo(e)pyrene	decreases methylation	1
4-hydroxy-2-nonenal	decreases expression	1
1-hydroxypyrene	affects cotreatment, decreases methylation	1
HC toxin	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
dibenzo(a,l)pyrene	decreases expression	1
chromium hexavalent ion	decreases activity	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	increases reaction, affects binding	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression	1
bisphenol B	increases expression	1

ChEMBL screening assays

514 unique, capped per target: 509 binding, 3 admet, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1009922	Binding	Inhibition of Yes	Fragment-based discovery of the pyrazol-4-yl urea (AT9283), a multitargeted kinase inhibitor with potent aurora kinase activity. — *J Med Chem*
CHEMBL2354304	Functional	PubChem BioAssay. qHTS for small molecule inhibitors of Yes1 kinase: Confirmatory screen on the cherrypicks. (Class of assay: confirmatory)	PubChem BioAssay data set
CHEMBL4313108	ADMET	Inhibition of recombinant full-length human Yes at 100 nM using poly(Glu, Tyr) 4:1 as substrate measured after 40 mins in presence of [gamma33P]ATP by scintillation counting method	Discovery and Development of a Series of Pyrazolo[3,4-d]pyridazinone Compounds as the Novel Covalent Fibroblast Growth Factor Receptor Inhibitors by the Rational Drug Design. — *J Med Chem*

Cellosaurus cell lines

6 cell lines: 6 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2LK	Abcam HeLa YES1 KO	Cancer cell line	Female
CVCL_C8IN	K562/fes clone WS-1	Cancer cell line	Female
CVCL_C8IP	K562/fes clone WS-5	Cancer cell line	Female
CVCL_C8IQ	K562/fes clone WS-6	Cancer cell line	Female
CVCL_TY45	HAP1 YES1 (-) 1	Cancer cell line	Male
CVCL_TY46	HAP1 YES1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for YES1 across ~30M SureChEMBL compounds — explore on Sugi Predict.