CABLES1

Summary

CABLES1 (Cdk5 and Abl enzyme substrate 1, HGNC:25097) is a protein-coding gene on chromosome 18q11.2, encoding CDK5 and ABL1 enzyme substrate 1 (Q8TDN4). Cyclin-dependent kinase binding protein.

This gene encodes a protein involved in regulation of the cell cycle through interactions with several cyclin-dependent kinases. One study (PMID: 16177568) reported aberrant splicing of transcripts from this gene which results in removal of the cyclin binding domain only in human cancer cells, and reduction in gene expression was shown in colorectal cancers (PMID: 17982127).Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 91768 — RefSeq curated summary.

At a glance

• GWAS associations: 124
• Clinical variants (ClinVar): 135 total
• Druggable target: yes
• MANE Select transcript: NM_001100619

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25097
Approved symbol	CABLES1
Name	Cdk5 and Abl enzyme substrate 1
Location	18q11.2
Locus type	gene with protein product
Status	Approved
Aliases	HsT2563, FLJ35924
Ensembl gene	ENSG00000134508
Ensembl biotype	protein_coding
OMIM	609194
Entrez	91768

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 8 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000256925, ENST00000400473, ENST00000420687, ENST00000578052, ENST00000579963, ENST00000580153, ENST00000580644, ENST00000582882, ENST00000583220, ENST00000585061, ENST00000877774, ENST00000912383, ENST00000952329

RefSeq mRNA: 3 — MANE Select: NM_001100619 NM_001100619, NM_001256438, NM_138375

CCDS: CCDS42417, CCDS42418, CCDS58615

Canonical transcript exons

ENST00000256925 — 10 exons

Exon	Start	End
ENSE00001313025	23135485	23136607
ENSE00001637853	23257227	23260470
ENSE00001669048	23237142	23237245
ENSE00001670351	23234608	23234704
ENSE00001672482	23213977	23214054
ENSE00001748200	23235895	23236051
ENSE00003540257	23253729	23253936
ENSE00003586402	23252960	23253066
ENSE00003710390	23194448	23194540
ENSE00003711280	23188838	23188909

Expression profiles

Bgee: expression breadth ubiquitous, 218 present calls, max score 93.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.0323 / max 285.9530, expressed in 1378 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
169661	8.7993	1304
169662	0.6131	114
208516	0.4241	224
169660	0.1958	124

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
putamen	UBERON:0001874	93.93	gold quality
caudate nucleus	UBERON:0001873	93.57	gold quality
nucleus accumbens	UBERON:0001882	93.57	gold quality
medial globus pallidus	UBERON:0002477	93.00	gold quality
kidney epithelium	UBERON:0004819	92.57	silver quality
globus pallidus	UBERON:0001875	92.54	gold quality
lateral globus pallidus	UBERON:0002476	92.52	gold quality
amygdala	UBERON:0001876	91.85	gold quality
lower esophagus mucosa	UBERON:0035834	90.91	gold quality
temporal lobe	UBERON:0001871	90.65	gold quality
pancreatic ductal cell	CL:0002079	89.84	silver quality
substantia nigra pars reticulata	UBERON:0001966	89.63	gold quality
right frontal lobe	UBERON:0002810	89.61	gold quality
entorhinal cortex	UBERON:0002728	89.57	gold quality
anterior cingulate cortex	UBERON:0009835	89.15	gold quality
sural nerve	UBERON:0015488	89.10	gold quality
tibialis anterior	UBERON:0001385	88.82	silver quality
buccal mucosa cell	CL:0002336	88.76	gold quality
postcentral gyrus	UBERON:0002581	88.56	gold quality
substantia nigra	UBERON:0002038	88.37	gold quality
superior frontal gyrus	UBERON:0002661	88.26	gold quality
parietal lobe	UBERON:0001872	88.14	gold quality
midbrain	UBERON:0001891	87.99	gold quality
primary visual cortex	UBERON:0002436	87.57	gold quality
ventral tegmental area	UBERON:0002691	87.41	gold quality
tendon of biceps brachii	UBERON:0008188	87.41	silver quality
frontal cortex	UBERON:0001870	87.22	gold quality
neocortex	UBERON:0001950	86.97	gold quality
substantia nigra pars compacta	UBERON:0001965	86.95	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	86.88	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	21.62
E-ANND-3	yes	11.18

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53, TP73

miRNA regulators (miRDB)

75 targeting CABLES1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538

Literature-anchored findings (GeneRIF, showing 11)

• Analysis of the RT-PCR prducts of the CABLES1 gene showed eight intragenic deletions in its mRNA transcripts; 5/8 are the result of RNA splicing. (PMID:16177568)
• Loss of Cables expression in 65% of CRCs suggests that it is a common event in colonic carcinogenesis, with promoter methylation and LOH appearing to be important mechanisms of Cables gene inactivation. (PMID:17982127)
• Mechanisms of CABLES1 gene inactivation in ovarian cancer development are reported. (PMID:18059193)
• The results did not detect a significant association. It indicated that common genetic variations in CDK5 genes might not play a role in the genetic predisposition to autism. (PMID:21890215)
• the results suggest Cables1 as a novel p21 regulator through maintaining p21 stability and support the model that the tumor-suppressive function of Cables1 occurs at least in part through enhancing the tumor-suppressive activity of p21. (PMID:24975575)
• Results illuminated a dynamic regulatory system through which activated Akt and 14-3-3 work directly together to neutralize a potent tumor suppressor function of Cables1. (PMID:25361894)
• CABLES1 is a critical regulator of corticotrope proliferation that defines a pathway often inactivated in Cushing disease (PMID:26695862)
• Cables1/p21 pathway has a strong effect on the induction of cell senescence and inhibition of cell growth, and acts as a novel regulatory mechanism in which p21 is probably one of several downstream effector molecules to mediate Cables1. (PMID:28118639)
• We have identified four potentially pathogenic missense CABLES1 variants as a novel, although infrequent, cause of Cushing’s Disease in children and young adults. (PMID:28533356)
• miR199a-3p and P53 are coupled through CABLES1 and comprise a novel negative feedback loop that likely contributes to cardiac c-kit(+) cell proliferation and apoptosis. (PMID:28583208)
• CABLES1 expression is reduced in human subcutaneous adipose tissue in obesity and type 2 diabetes but may not directly impact adipocyte glucose and lipid metabolism. (PMID:37555665)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cables1	ENSDARG00000099395
mus_musculus	Cables1	ENSMUSG00000040957
rattus_norvegicus	Cables1	ENSRNOG00000012795
drosophila_melanogaster	CG6191	FBGN0027581
caenorhabditis_elegans	Y71F9B.6	WBGENE00022128

Paralogs (1): CABLES2 (ENSG00000149679)

Protein

Protein identifiers

CDK5 and ABL1 enzyme substrate 1 — Q8TDN4 (reviewed: Q8TDN4)

Alternative names: Interactor with CDK3 1

All UniProt accessions (5): A0A0G2JLG8, A7K6Y5, J3QRY5, Q8TDN4, V9GYB4

UniProt curated annotations — full annotation on UniProt →

Function. Cyclin-dependent kinase binding protein. Enhances cyclin-dependent kinase tyrosine phosphorylation by nonreceptor tyrosine kinases, such as that of CDK5 by activated ABL1, which leads to increased CDK5 activity and is critical for neuronal development, and that of CDK2 by WEE1, which leads to decreased CDK2 activity and growth inhibition. Positively affects neuronal outgrowth. Plays a role as a regulator for p53/p73-induced cell death.

Subunit / interactions. Found in a complex with p53/TP53. Found in a number of complexes with CDK2, CDK3, CDK5, ABL1, TDRD7, CDK17, CCNA1, CCNE1 and TP73. Interacts with CDK2, CDK3, CDK5, ABL1 and TDRD7.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Expressed in breast, pancreas, colon, head and neck (at protein level). Strongly decreased in more than half of cases of atypical endometrial hyperplasia and in more than 90% of endometrial cancers.

Post-translational modifications. Phosphorylated on Ser-313 by CCNE1/CDK3. Phosphorylated on serine/threonine residues by CDK5 and on tyrosine residues by ABL1. Also phosphorylated in vitro by CCNA1/CDK2, CCNE1/CDK2, CCNA1/CDK3 and CCNE1/CDK3.

Induction. Up-regulated by progesterone and down-regulated by estrogen in benign endometrium.

Similarity. Belongs to the cyclin family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q8TDN4-1	1	yes
Q8TDN4-2	2
Q8TDN4-3	3
Q8TDN4-4	4

RefSeq proteins (3): NP_001094089, NP_001243367, NP_612384 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006671	Cyclin_N	Domain
IPR012388	CABLES1/2	Family
IPR036915	Cyclin-like_sf	Homologous_superfamily

Pfam: PF00134

UniProt features (15 total): splice variant 4, modified residue 4, region of interest 3, compositionally biased region 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TDN4-F1	57.66	0.11

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): 168, 287, 313, 415

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-69202	Cyclin E associated events during G1/S transition
R-HSA-69656	Cyclin A:Cdk2-associated events at S phase entry
R-HSA-983231	Factors involved in megakaryocyte development and platelet production
R-HSA-109582	Hemostasis
R-HSA-1640170	Cell Cycle
R-HSA-453279	Mitotic G1 phase and G1/S transition
R-HSA-69206	G1/S Transition
R-HSA-69242	S Phase
R-HSA-69278	Cell Cycle, Mitotic

MSigDB gene sets: 139 (showing top): GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_DN, FERREIRA_EWINGS_SARCOMA_UNSTABLE_VS_STABLE_DN, GOBP_REGULATION_OF_CELL_CYCLE, MCBRYAN_PUBERTAL_BREAST_3_4WK_UP, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, TGACATY_UNKNOWN, PID_AJDISS_2PATHWAY, BENPORATH_NOS_TARGETS, POU3F2_02, DOUGLAS_BMI1_TARGETS_UP, CUI_TCF21_TARGETS_2_DN, CART1_01, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, CTCTATG_MIR368, chr18q11

GO Biological Process (3): nervous system development (GO:0007399), cell division (GO:0051301), regulation of cell cycle (GO:0051726)

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

GO Cellular Component (3): nucleus (GO:0005634), cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Cell Cycle, Mitotic	2
G1/S Transition	1
S Phase	1
Hemostasis	1
Mitotic G1 phase and G1/S transition	1
Cell Cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
system development	1
cellular process	1
cell cycle	1
regulation of cellular process	1
binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

642 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CABLES1	CDK3	Q00526	945
CABLES1	TDRD7	Q8NHU6	898
CABLES1	CDK17	Q00537	882
CABLES1	CDK18	Q07002	754
CABLES1	TP53	P04637	734
CABLES1	WEE1	P30291	696
CABLES1	CDK5	Q00535	640
CABLES1	CDK16	Q00536	637
CABLES1	CCDC180	Q9P1Z9	589
CABLES1	CCNL2	Q96S94	530
CABLES1	CDK5R1	Q15078	520
CABLES1	CDK2	P24941	509
CABLES1	CCNA1	P78396	495
CABLES1	CCNA2	P20248	483
CABLES1	SLC35D4	Q24JQ0	480

IntAct

48 interactions, top by confidence:

A	B	Type	Score
CDK5	CABLES1	psi-mi:“MI:0915”(physical association)	0.890
CDK5	FIBP	psi-mi:“MI:0914”(association)	0.840
FIBP	CDK5	psi-mi:“MI:0914”(association)	0.840
TP53	CABLES1	psi-mi:“MI:0915”(physical association)	0.540
CABLES1	TP53	psi-mi:“MI:2364”(proximity)	0.540
DLK1	TCAF2	psi-mi:“MI:0914”(association)	0.530
TP63	CABLES1	psi-mi:“MI:0915”(physical association)	0.470
CABLES1	TP63	psi-mi:“MI:0915”(physical association)	0.470
CABLES1	TP63	psi-mi:“MI:2364”(proximity)	0.470
CABLES1	EXOSC8	psi-mi:“MI:0915”(physical association)	0.400
ALB	CNOT1	psi-mi:“MI:0914”(association)	0.350
FIBP	CDK5	psi-mi:“MI:0914”(association)	0.350
CDK5	CDK14	psi-mi:“MI:0914”(association)	0.350
GOPC	ZBTB5	psi-mi:“MI:0914”(association)	0.350
ZCCHC10	C1orf226	psi-mi:“MI:0914”(association)	0.350
PRPS2	SMCHD1	psi-mi:“MI:0914”(association)	0.350
FIBP	DNM1L	psi-mi:“MI:0914”(association)	0.350
FGFR4	SH3PXD2B	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (63): CABLES1 (Affinity Capture-MS), CABLES1 (Affinity Capture-MS), CABLES1 (Affinity Capture-MS), CABLES1 (Affinity Capture-MS), CABLES1 (Affinity Capture-MS), CABLES1 (Affinity Capture-MS), CABLES1 (Affinity Capture-MS), CABLES1 (Affinity Capture-MS), CABLES1 (Affinity Capture-RNA), CABLES1 (Affinity Capture-MS), CABLES1 (Affinity Capture-Western), AKT1 (Affinity Capture-Western), CDKN1A (Affinity Capture-Western), CABLES1 (Affinity Capture-Western), CABLES1 (Affinity Capture-MS)

ESM2 similar proteins: A0A2K3DDJ2, A2A9A2, A2VDX9, A2Y5N0, A4GRC6, A6QQ94, A8ICS9, A8ID95, A8INQ0, A8ITB0, A8ITV9, A8J666, A8JID5, F5A894, O83683, P09695, P09715, P14348, P17473, P24096, P28925, P30662, P54817, Q01JD1, Q08354, Q08355, Q08356, Q10MB4, Q2QPW2, Q49I55, Q49I57, Q4VKB4, Q5QD03, Q6AYU4, Q6F5E0, Q6L4N4, Q6S6U0, Q6SVX2, Q6SW04, Q7XT42

Diamond homologs: Q8K3M5, Q8TDN4, Q9BTV7, Q9ESJ1

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
CDK5	unknown	CABLES1	phosphorylation
CDK3	unknown	CABLES1	phosphorylation
CyclinE1/CDK3	unknown	CABLES1	phosphorylation
AKT1	“down-regulates activity”	CABLES1	phosphorylation
14-3-3	“down-regulates activity”	CABLES1	binding
CABLES1	“down-regulates activity”	CDK2	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	114
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2340 predictions. Top by Δscore:

Variant	Effect	Δscore
18:23136607:GGT:G	donor_loss	1.0000
18:23136608:G:GG	donor_gain	1.0000
18:23136608:GTGA:G	donor_loss	1.0000
18:23136609:T:A	donor_loss	1.0000
18:23188834:GCAG:G	acceptor_loss	1.0000
18:23188835:CAGAC:C	acceptor_loss	1.0000
18:23188836:A:AG	acceptor_gain	1.0000
18:23188836:A:C	acceptor_loss	1.0000
18:23188836:AGAC:A	acceptor_gain	1.0000
18:23188836:AGACG:A	acceptor_gain	1.0000
18:23188837:G:GG	acceptor_gain	1.0000
18:23188837:GA:G	acceptor_gain	1.0000
18:23188837:GAC:G	acceptor_gain	1.0000
18:23188837:GACG:G	acceptor_gain	1.0000
18:23188837:GACGG:G	acceptor_gain	1.0000
18:23188906:GGAG:G	donor_gain	1.0000
18:23188907:G:GT	donor_gain	1.0000
18:23188907:GAG:G	donor_gain	1.0000
18:23188908:AGG:A	donor_loss	1.0000
18:23188909:GGTA:G	donor_loss	1.0000
18:23188910:G:GG	donor_gain	1.0000
18:23188911:T:A	donor_loss	1.0000
18:23213976:GAATA:G	acceptor_gain	1.0000
18:23237130:T:G	acceptor_gain	1.0000
18:23252948:T:TA	acceptor_gain	1.0000
18:23252952:T:TA	acceptor_gain	1.0000
18:23252958:A:AG	acceptor_gain	1.0000
18:23252958:A:G	acceptor_loss	1.0000
18:23252959:G:GA	acceptor_gain	1.0000
18:23252959:GA:G	acceptor_gain	1.0000

AlphaMissense

4087 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:23213982:T:A	V339D	1.000
18:23237184:T:C	L462S	1.000
18:23237198:T:A	W467R	1.000
18:23237198:T:C	W467R	1.000
18:23237200:G:C	W467C	1.000
18:23237200:G:T	W467C	1.000
18:23237213:C:G	H472D	1.000
18:23237218:A:C	K473N	1.000
18:23237218:A:T	K473N	1.000
18:23237226:T:C	L476P	1.000
18:23237232:T:C	F478S	1.000
18:23252994:T:A	L494H	1.000
18:23252994:T:C	L494P	1.000
18:23252996:A:G	K495E	1.000
18:23252998:G:C	K495N	1.000
18:23252998:G:T	K495N	1.000
18:23253008:A:C	N499H	1.000
18:23253008:A:G	N499D	1.000
18:23253010:C:A	N499K	1.000
18:23253010:C:G	N499K	1.000
18:23253017:T:C	F502L	1.000
18:23253018:T:C	F502S	1.000
18:23253019:C:A	F502L	1.000
18:23253019:C:G	F502L	1.000
18:23253045:T:C	L511P	1.000
18:23253048:C:T	T512I	1.000
18:23253051:T:A	L513H	1.000
18:23253051:T:C	L513P	1.000
18:23253053:A:C	S514R	1.000
18:23253054:G:T	S514I	1.000

dbSNP variants (sampled 300 via entrez): RS1000031052 (18:23144906 G>A), RS1000102299 (18:23219114 C>G,T), RS1000117304 (18:23188973 G>C,T), RS1000149411 (18:23212488 A>G), RS1000151791 (18:23212303 G>A), RS1000158640 (18:23139154 C>A,T), RS1000176707 (18:23237369 G>A,C), RS1000178328 (18:23215898 C>T), RS1000211693 (18:23138917 C>T), RS1000215184 (18:23178017 C>T), RS1000220667 (18:23134874 G>T), RS1000221057 (18:23191261 C>T), RS1000252127 (18:23215670 G>C), RS1000320998 (18:23259679 A>G), RS1000347038 (18:23248431 G>A)

Disease associations

OMIM: gene MIM:609194 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

124 associations (top):

Study	Trait	p-value
GCST000175_6	Height	4.000000e-09
GCST000349_19	Smoking behavior	6.000000e-06
GCST000611_22	Height	3.000000e-06
GCST000764_14	Tuberculosis	7.000000e-09
GCST000817_67	Height	4.000000e-30
GCST001337_53	Platelet count	5.000000e-11
GCST001905_6	Hypertriglyceridemia	2.000000e-08
GCST001956_53	Height	5.000000e-15
GCST002186_2	Platelet count	5.000000e-06
GCST002647_156	Height	2.000000e-53
GCST002702_104	Height	5.000000e-24
GCST002843_8	Sitting height ratio	7.000000e-07
GCST003474_9	Scalp hair shape	6.000000e-06
GCST004063_128	Waist circumference adjusted for body mass index	1.000000e-14
GCST004063_130	Waist circumference adjusted for body mass index	1.000000e-22
GCST004063_136	Waist circumference adjusted for body mass index	1.000000e-11
GCST004067_131	Hip circumference adjusted for BMI	2.000000e-07
GCST004067_198	Hip circumference adjusted for BMI	6.000000e-11
GCST004067_87	Hip circumference adjusted for BMI	3.000000e-15
GCST004212_2	Height	4.000000e-12
GCST004500_25	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	2.000000e-22
GCST004500_74	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	8.000000e-14
GCST004500_87	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	9.000000e-13
GCST004501_34	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	5.000000e-24
GCST004501_35	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	4.000000e-14
GCST004501_9	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	4.000000e-13
GCST004503_9	Waist circumference adjusted for BMI in smokers	1.000000e-07
GCST004504_12	Waist circumference adjusted for BMI in non-smokers	1.000000e-11
GCST004504_13	Waist circumference adjusted for BMI in non-smokers	3.000000e-19
GCST004504_14	Waist circumference adjusted for BMI in non-smokers	6.000000e-11

EFO canonical traits (21, from GWAS)

EFO ID	Trait name
EFO:0004318	smoking behavior
EFO:0004309	platelet count
EFO:0004530	triglyceride measurement
EFO:0007118	sitting height ratio
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference
EFO:0008002	physical activity measurement
EFO:0007985	platelet crit
EFO:0007984	platelet component distribution width
EFO:0005091	monocyte count
EFO:0008434	initial pursuit acceleration
EFO:0004312	vital capacity
EFO:0009270	heel bone mineral density
EFO:0004341	body fat distribution
EFO:0004314	forced expiratory volume
EFO:0004324	body weights and measures
EFO:0004344	birth weight
EFO:0006797	neurofibrillary tangles measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067090 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
7.02	Kd	96.05	nM	CHEMBL5653589
6.76	ED50	174.8	nM	CHEMBL5653589
6.26	Kd	545.8	nM	CHEMBL3752910
6.00	ED50	993.1	nM	CHEMBL3752910

PubChem BioAssay actives

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

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147977: Binding affinity to human CABLES1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0960	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147977: Binding affinity to human CABLES1 incubated for 45 mins by Kinobead based pull down assay	kd	0.5457	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, increases methylation, affects cotreatment, decreases expression	5
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation, increases expression, increases methylation	4
Estradiol	affects cotreatment, increases expression	3
Decitabine	affects expression, affects methylation	2
Cisplatin	affects expression, decreases expression	2
Nickel	decreases expression	2
Quercetin	decreases expression, decreases phosphorylation	2
Tretinoin	decreases expression	2
Zearalenone	increases expression	2
Genistein	increases expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
methylmercuric chloride	increases expression	1
o,p’-DDT	increases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	decreases expression	1
aflatoxin B2	decreases methylation	1
nickel sulfate	increases expression	1
coumarin	increases phosphorylation	1
cyanoginosin LR	increases expression	1
CGP 52608	affects binding, increases reaction	1
belinostat	decreases expression	1
quinocetone	decreases expression	1
NSC 689534	decreases expression, affects binding	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Leflunomide	increases expression	1
Arsenic	decreases methylation, increases abundance	1
Caffeine	increases phosphorylation	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
CHEMBL5651019	Binding	Binding affinity to human CABLES1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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