CABLES2

Summary

CABLES2 (Cdk5 and Abl enzyme substrate 2, HGNC:16143) is a protein-coding gene on chromosome 20q13.33, encoding CDK5 and ABL1 enzyme substrate 2 (Q9BTV7). Unknown.

Predicted to be involved in cell division and regulation of cell cycle.

Source: NCBI Gene 81928 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 113 total
• MANE Select transcript: NM_031215

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16143
Approved symbol	CABLES2
Name	Cdk5 and Abl enzyme substrate 2
Location	20q13.33
Locus type	gene with protein product
Status	Approved
Aliases	dJ908M14.2, ik3-2
Ensembl gene	ENSG00000149679
Ensembl biotype	protein_coding
OMIM	618772
Entrez	81928

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000279101, ENST00000453274, ENST00000923983, ENST00000971783

RefSeq mRNA: 1 — MANE Select: NM_031215 NM_031215

CCDS: CCDS33503

Canonical transcript exons

ENST00000279101 — 10 exons

Exon	Start	End
ENSE00000991941	62394157	62394265
ENSE00001671627	62396521	62396592
ENSE00001687530	62392920	62393023
ENSE00001709987	62393440	62393605
ENSE00001748969	62391249	62391453
ENSE00001803963	62392389	62392495
ENSE00001806302	62396315	62396407
ENSE00001820608	62406915	62407285
ENSE00001877184	62388634	62391111
ENSE00003594892	62394937	62395014

Expression profiles

Bgee: expression breadth ubiquitous, 208 present calls, max score 94.42.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.2275 / max 133.8733, expressed in 1656 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
188266	6.2172	1656
188265	0.0103	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	94.42	gold quality
left testis	UBERON:0004533	88.82	gold quality
cardiac muscle of right atrium	UBERON:0003379	88.52	silver quality
right testis	UBERON:0004534	88.35	gold quality
testis	UBERON:0000473	87.83	gold quality
adult organism	UBERON:0007023	86.89	gold quality
heart right ventricle	UBERON:0002080	86.56	silver quality
Brodmann (1909) area 23	UBERON:0013554	86.16	gold quality
ileal mucosa	UBERON:0000331	86.01	silver quality
endothelial cell	CL:0000115	85.93	silver quality
ganglionic eminence	UBERON:0004023	83.90	gold quality
cortical plate	UBERON:0005343	83.41	gold quality
middle temporal gyrus	UBERON:0002771	82.29	silver quality
right hemisphere of cerebellum	UBERON:0014890	82.15	gold quality
primary visual cortex	UBERON:0002436	81.92	gold quality
ventricular zone	UBERON:0003053	81.61	gold quality
cerebellar hemisphere	UBERON:0002245	81.39	gold quality
cardiac atrium	UBERON:0002081	81.30	gold quality
apex of heart	UBERON:0002098	81.30	gold quality
cerebellar cortex	UBERON:0002129	81.29	gold quality
cerebellum	UBERON:0002037	81.16	gold quality
right atrium auricular region	UBERON:0006631	80.86	gold quality
occipital lobe	UBERON:0002021	79.65	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.56	gold quality
stromal cell of endometrium	CL:0002255	78.76	gold quality
cardiac ventricle	UBERON:0002082	78.71	gold quality
right frontal lobe	UBERON:0002810	78.64	gold quality
heart left ventricle	UBERON:0002084	78.55	gold quality
pancreatic ductal cell	CL:0002079	78.34	silver quality
epithelial cell of pancreas	CL:0000083	78.33	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.99

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

136 targeting CABLES2, 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-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505

Literature-anchored findings (GeneRIF, showing 1)

• We thus identified ik3-2 as a proapoptotic factor involved in both p53-mediated and p53-independent apoptotic pathways. (PMID:14637168)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	cables2b	ENSDARG00000017154
danio_rerio	cables2a	ENSDARG00000076964
mus_musculus	Cables2	ENSMUSG00000038990
rattus_norvegicus	Cables2	ENSRNOG00000051420
drosophila_melanogaster	CG6191	FBGN0027581
caenorhabditis_elegans	Y71F9B.6	WBGENE00022128

Paralogs (1): CABLES1 (ENSG00000134508)

Protein

Protein identifiers

CDK5 and ABL1 enzyme substrate 2 — Q9BTV7 (reviewed: Q9BTV7)

Alternative names: Interactor with CDK3 2

All UniProt accessions (2): Q9BTV7, H0Y5H2

UniProt curated annotations — full annotation on UniProt →

Function. Unknown. Probably involved in G1-S cell cycle transition.

Subunit / interactions. Binds to CDK3, CDK5 and ABL1. The C-terminal cyclin-box-like region binds to CDK5.

Similarity. Belongs to the cyclin family.

RefSeq proteins (1): NP_112492* (*=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 (11 total): compositionally biased region 4, region of interest 2, modified residue 2, chain 1, sequence conflict 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BTV7-F1	61.39	0.25

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 (2): 130, 208

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-983231	Factors involved in megakaryocyte development and platelet production
R-HSA-109582	Hemostasis

MSigDB gene sets: 105 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, PATIL_LIVER_CANCER, VART_KSHV_INFECTION_ANGIOGENIC_MARKERS_UP, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, GOBP_REGULATION_OF_CELL_CYCLE, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, GOBP_GASTRULATION, GOBP_DNA_DAMAGE_RESPONSE, GOBP_SIGNAL_TRANSDUCTION_BY_P53_CLASS_MEDIATOR, GOBP_SIGNAL_TRANSDUCTION_IN_RESPONSE_TO_DNA_DAMAGE, GOBP_EMBRYO_DEVELOPMENT, GOBP_CELL_DIVISION, GOBP_EMBRYONIC_MORPHOGENESIS, NIKOLSKY_BREAST_CANCER_20Q12_Q13_AMPLICON

GO Biological Process (2): cell division (GO:0051301), regulation of cell cycle (GO:0051726)

GO Molecular Function (0):

GO Cellular Component (1): cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Hemostasis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	1
cell cycle	1
regulation of cellular process	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

508 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CABLES2	RBBP8NL	Q8NC74	599
CABLES2	ABL1	P00519	462
CABLES2	CDK3	Q00526	441
CABLES2	PLAGL2	Q9UPG8	418
CABLES2	SH3BP1	Q9Y3L3	417
CABLES2	CDADC1	Q9BWV3	408
CABLES2	RPS21	P35265	406
CABLES2	ALG1L2	C9J202	394
CABLES2	LAMA5	O15230	393
CABLES2	TM9SF4	Q92544	383
CABLES2	ADPRM	Q3LIE5	381
CABLES2	GATA5	Q9BWX5	368
CABLES2	METTL13	Q8N6R0	364
CABLES2	PLPP6	Q8IY26	348
CABLES2	RNF220	Q5VTB9	336

IntAct

22 interactions, top by confidence:

A	B	Type	Score
CDK5	FIBP	psi-mi:“MI:0914”(association)	0.840
FIBP	CDK5	psi-mi:“MI:0914”(association)	0.840
DLK1	TCAF2	psi-mi:“MI:0914”(association)	0.530
ZNRD2	KRBA1	psi-mi:“MI:0914”(association)	0.350
FIBP	CDK5	psi-mi:“MI:0914”(association)	0.350
PIPSL	C1orf226	psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
GCH1	ARHGAP42	psi-mi:“MI:0914”(association)	0.350
TNFRSF1B	MAP3K7	psi-mi:“MI:0914”(association)	0.350
FIBP	DNM1L	psi-mi:“MI:0914”(association)	0.350
DLK1	PLPP3	psi-mi:“MI:0914”(association)	0.350
FIBP	AGRN	psi-mi:“MI:0914”(association)	0.350
FTL		psi-mi:“MI:0914”(association)	0.350
SDC1	TCAF2	psi-mi:“MI:0914”(association)	0.350

BioGRID (30): CABLES2 (Affinity Capture-MS), CABLES2 (Affinity Capture-MS), CABLES2 (Affinity Capture-MS), CABLES2 (Affinity Capture-MS), CABLES2 (Affinity Capture-MS), CABLES2 (Affinity Capture-MS), CABLES2 (Affinity Capture-RNA), CABLES2 (Affinity Capture-Western), CABLES2 (Affinity Capture-MS), CDK3 (Affinity Capture-Western), CDK5 (Affinity Capture-Western), ABL1 (Affinity Capture-Western), CABLES2 (Affinity Capture-RNA), CABLES2 (Affinity Capture-MS), CABLES2 (Affinity Capture-MS)

ESM2 similar proteins: A0A5N6H279, A4D2B8, D3ZML2, O76081, O91531, P03327, P0C678, P0C733, P79348, Q00731, Q09PK2, Q13670, Q1HVB5, Q1ZZU3, Q4KL35, Q4R1S1, Q52993, Q5JLA7, Q5JN07, Q5MFW3, Q63553, Q64902, Q6DN03, Q6NUI1, Q6P050, Q6SW81, Q86UQ5, Q8AZJ3, Q8BG31, Q8BVZ5, Q8CE90, Q8CEZ0, Q8K3M5, Q8LN49, Q8N5Z5, Q8TE04, Q8VDU5, Q8WTX9, Q8WXT5, Q9BTV7

Diamond homologs: Q8K3M5, Q8TDN4, Q9BTV7, Q9ESJ1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	98
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1688 predictions. Top by Δscore:

Variant	Effect	Δscore
20:62391109:CTT:C	acceptor_gain	1.0000
20:62391242:CACT:C	donor_loss	1.0000
20:62391243:ACTC:A	donor_loss	1.0000
20:62391244:CTCA:C	donor_loss	1.0000
20:62391245:TCA:T	donor_loss	1.0000
20:62391247:A:AC	donor_gain	1.0000
20:62391248:C:CT	donor_gain	1.0000
20:62391248:CA:C	donor_gain	1.0000
20:62391248:CAT:C	donor_gain	1.0000
20:62391248:CATCG:C	donor_gain	1.0000
20:62391449:TTAAG:T	acceptor_gain	1.0000
20:62391450:TAAG:T	acceptor_gain	1.0000
20:62391451:AAG:A	acceptor_gain	1.0000
20:62391452:AG:A	acceptor_gain	1.0000
20:62391453:GC:G	acceptor_loss	1.0000
20:62391454:C:CC	acceptor_gain	1.0000
20:62392383:CCTCA:C	donor_loss	1.0000
20:62392384:CTCA:C	donor_loss	1.0000
20:62392385:TCA:T	donor_loss	1.0000
20:62392386:CA:C	donor_loss	1.0000
20:62392387:ACCT:A	donor_gain	1.0000
20:62392388:C:G	donor_loss	1.0000
20:62392388:CCTC:C	donor_gain	1.0000
20:62392390:T:TA	donor_gain	1.0000
20:62392491:GTGGT:G	acceptor_gain	1.0000
20:62392492:TGGT:T	acceptor_gain	1.0000
20:62392493:GGT:G	acceptor_gain	1.0000
20:62392493:GGTC:G	acceptor_loss	1.0000
20:62392494:GT:G	acceptor_gain	1.0000
20:62392494:GTC:G	acceptor_loss	1.0000

AlphaMissense

3063 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:62392397:T:A	K361N	1.000
20:62392397:T:G	K361N	1.000
20:62392398:T:A	K361I	1.000
20:62392457:T:A	K341N	1.000
20:62392457:T:G	K341N	1.000
20:62392461:A:G	L340P	1.000
20:62392461:A:T	L340H	1.000
20:62392485:A:T	I332K	1.000
20:62392932:A:C	F324L	1.000
20:62392932:A:T	F324L	1.000
20:62392933:A:G	F324S	1.000
20:62392934:A:G	F324L	1.000
20:62392939:A:G	L322P	1.000
20:62392947:T:A	K319N	1.000
20:62392947:T:G	K319N	1.000
20:62392952:G:C	H318D	1.000
20:62392957:C:T	G316D	1.000
20:62392965:C:A	W313C	1.000
20:62392965:C:G	W313C	1.000
20:62392967:A:G	W313R	1.000
20:62392967:A:T	W313R	1.000
20:62391050:A:G	L453P	0.999
20:62391050:A:T	L453H	0.999
20:62391074:A:G	L445P	0.999
20:62391298:G:T	A416D	0.999
20:62391299:C:G	A416P	0.999
20:62391301:G:T	A415D	0.999
20:62391304:A:G	L414P	0.999
20:62391307:A:G	L413P	0.999
20:62391312:G:C	C411W	0.999

dbSNP variants (sampled 300 via entrez): RS1000247333 (20:62397238 G>A), RS1000513001 (20:62393824 T>C), RS1000839010 (20:62397060 C>A), RS1000849116 (20:62392864 C>A,G,T), RS1000887651 (20:62389308 T>C,G), RS1000988991 (20:62398568 C>T), RS1001078463 (20:62389111 A>G), RS1001102535 (20:62402536 C>T), RS1001223611 (20:62392624 G>A,C,T), RS1001531395 (20:62396712 C>T), RS1001777164 (20:62401792 C>T), RS1001804152 (20:62392079 GAGGGGCCGGGCACAAC>G), RS1001866789 (20:62397764 C>T), RS1002043509 (20:62398296 G>A), RS1002291159 (20:62388758 C>T)

Disease associations

OMIM: gene MIM:618772 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001942_4	Prostate cancer	4.000000e-08
GCST005174_51	Coronary artery calcified atherosclerotic plaque score in type 2 diabetes	8.000000e-06
GCST005591_3	Colorectal cancer	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004723	coronary artery calcification

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	2
Arsenic	affects methylation, decreases expression, increases abundance	2
Benzo(a)pyrene	decreases expression, increases expression	2
dicrotophos	increases expression	1
beta-lapachone	decreases expression	1
abrine	decreases expression	1
bisphenol S	affects cotreatment, decreases methylation	1
Temozolomide	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation, increases methylation	1
Acetaminophen	increases expression	1
Cadmium	decreases expression, increases abundance	1
Cisplatin	decreases expression	1
Demecolcine	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects binding, increases expression	1
Niclosamide	decreases expression	1
Smoke	decreases expression	1
Valproic Acid	increases methylation	1
Vincristine	decreases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1
Okadaic Acid	increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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