SBK3

Summary

SBK3 (SH3 domain binding kinase family member 3, HGNC:44121) is a protein-coding gene on chromosome 19q13.42, encoding Uncharacterized serine/threonine-protein kinase SBK3 (P0C264).

Predicted to enable protein serine/threonine kinase activity. Predicted to be involved in chromatin remodeling.

Source: NCBI Gene 100130827 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 54 total
• Druggable target: yes — 10 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001199824

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:44121
Approved symbol	SBK3
Name	SH3 domain binding kinase family member 3
Location	19q13.42
Locus type	gene with protein product
Status	Approved
Aliases	SgK110
Ensembl gene	ENSG00000231274
Ensembl biotype	protein_coding
Entrez	100130827

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000592464, ENST00000612221, ENST00000850968, ENST00000850969, ENST00000850970, ENST00000953271

RefSeq mRNA: 1 — MANE Select: NM_001199824 NM_001199824

CCDS: CCDS74457

Canonical transcript exons

ENST00000612221 — 4 exons

Exon	Start	End
ENSE00004283070	55544799	55544949
ENSE00004283071	55544100	55544302
ENSE00004283072	55545499	55545543
ENSE00004283073	55540656	55541526

Expression profiles

Bgee: expression breadth broad, 95 present calls, max score 90.22.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right atrium auricular region	UBERON:0006631	90.22	gold quality
apex of heart	UBERON:0002098	79.10	gold quality
hindlimb stylopod muscle	UBERON:0004252	76.63	gold quality
heart	UBERON:0000948	75.29	gold quality
heart left ventricle	UBERON:0002084	74.42	gold quality
gastrocnemius	UBERON:0001388	74.19	gold quality
muscle of leg	UBERON:0001383	70.92	gold quality
skeletal muscle tissue	UBERON:0001134	62.73	gold quality
omental fat pad	UBERON:0010414	62.59	gold quality
adipose tissue	UBERON:0001013	60.81	gold quality
subcutaneous adipose tissue	UBERON:0002190	58.94	gold quality
lower esophagus mucosa	UBERON:0035834	58.62	gold quality
sural nerve	UBERON:0015488	58.05	gold quality
muscle tissue	UBERON:0002385	57.94	gold quality
right lung	UBERON:0002167	57.30	gold quality
thoracic mammary gland	UBERON:0005200	56.71	gold quality
right lobe of thyroid gland	UBERON:0001119	56.32	gold quality
duodenum	UBERON:0002114	53.03	gold quality
body of stomach	UBERON:0001161	51.77	gold quality
right coronary artery	UBERON:0001625	51.71	gold quality
gall bladder	UBERON:0002110	50.97	gold quality
upper lobe of left lung	UBERON:0008952	50.57	gold quality
left lobe of thyroid gland	UBERON:0001120	50.18	gold quality
thyroid gland	UBERON:0002046	50.00	gold quality
lower esophagus	UBERON:0013473	49.18	gold quality
lower esophagus muscularis layer	UBERON:0035833	49.12	gold quality
stomach	UBERON:0000945	49.03	gold quality
myometrium	UBERON:0001296	47.99	gold quality
fundus of stomach	UBERON:0001160	47.65	gold quality
smooth muscle tissue	UBERON:0001135	47.43	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.31

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

4 targeting SBK3, 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-6077	99.99	68.04	2299
HSA-MIR-6760-5P	98.87	66.73	1515
HSA-MIR-637	97.91	64.05	1517
HSA-MIR-1291	96.28	65.89	1224

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Sbk3	ENSMUSG00000085272
rattus_norvegicus	Sbk3	ENSRNOG00000042927
drosophila_melanogaster	meng	FBGN0031855
drosophila_melanogaster	CG4945	FBGN0034137
caenorhabditis_elegans		WBGENE00011299
caenorhabditis_elegans		WBGENE00012726

Paralogs (1): SBK1 (ENSG00000188322)

Protein

Protein identifiers

Uncharacterized serine/threonine-protein kinase SBK3 — P0C264 (reviewed: P0C264)

Alternative names: SH3 domain-binding kinase family member 3, Sugen kinase 110

All UniProt accessions (2): P0C264, K7EP79

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. STKL subfamily.

RefSeq proteins (1): NP_001186753* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site

Pfam: PF00069

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (7 total): binding site 2, chain 1, domain 1, region of interest 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0C264-F1	86.35	0.79

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): 163 (proton acceptor)

Ligand- & substrate-binding residues (2): 49–57; 72

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 8 (showing top): GOMF_PROTEIN_KINASE_ACTIVITY, GOMF_KINASE_ACTIVITY, GOMF_PROTEIN_SERINE_THREONINE_KINASE_ACTIVITY, GOMF_ADENYL_NUCLEOTIDE_BINDING, GOMF_TRANSFERASE_ACTIVITY_TRANSFERRING_PHOSPHORUS_CONTAINING_GROUPS, GOMF_PROTEIN_SERINE_KINASE_ACTIVITY, GOMF_PURINE_NUCLEOTIDE_BINDING, chr19q13

GO Biological Process (1): protein phosphorylation (GO:0006468)

GO Molecular Function (8): protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase activity	2
phosphorylation	1
protein modification process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate 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

Protein interactions and networks

STRING

206 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SBK3	Q3SXR2	Q3SXR2	581
SBK3	OR8B4	Q96RC9	526
SBK3	PRR32	B1ATL7	479
SBK3	RD3L	P0DJH9	477
SBK3	SMCO1	Q147U7	446
SBK3	ADCK5	Q3MIX3	433
SBK3	POMK	Q9H5K3	393
SBK3	TMEM108	Q6UXF1	348
SBK3	AATK	Q6ZMQ8	325
SBK3	TBCK	Q8TEA7	324
SBK3	TRAPPC11	Q7Z392	322
SBK3	SHKBP1	Q8TBC3	315
SBK3	RIOK1	Q9BRS2	314
SBK3	TEX14	Q8IWB6	307
SBK3	FAM86B1	Q8N7N1	306

IntAct

40 interactions, top by confidence:

A	B	Type	Score
SBK3	C1orf105	psi-mi:“MI:0915”(physical association)	0.560
SBK3	CRY2	psi-mi:“MI:0915”(physical association)	0.560
SBK3	SMAD3	psi-mi:“MI:0915”(physical association)	0.560
SBK3	AIMP2	psi-mi:“MI:0915”(physical association)	0.560
SBK3	GATAD2B	psi-mi:“MI:0915”(physical association)	0.560
SBK3	EXOSC2	psi-mi:“MI:0915”(physical association)	0.560
SBK3	POLDIP3	psi-mi:“MI:0915”(physical association)	0.560
SBK3	DMAP1	psi-mi:“MI:0915”(physical association)	0.560
SBK3	MBD3L2	psi-mi:“MI:0915”(physical association)	0.560
C1orf105	SBK3	psi-mi:“MI:0915”(physical association)	0.560
SBK3	TNNT1	psi-mi:“MI:0915”(physical association)	0.560
	SBK3	psi-mi:“MI:0915”(physical association)	0.560
NOTO	SBK3	psi-mi:“MI:0915”(physical association)	0.560
SBK3	SNRNP35	psi-mi:“MI:0915”(physical association)	0.560
SBK3	SMAD3	psi-mi:“MI:0915”(physical association)	0.000
AIMP2	SBK3	psi-mi:“MI:0915”(physical association)	0.000
SBK3	GATAD2B	psi-mi:“MI:0915”(physical association)	0.000
SBK3	NOTO	psi-mi:“MI:0915”(physical association)	0.000
SBK3	EXOSC2	psi-mi:“MI:0915”(physical association)	0.000
SBK3	POLDIP3	psi-mi:“MI:0915”(physical association)	0.000
SBK3	DMAP1	psi-mi:“MI:0915”(physical association)	0.000
SBK3	MBD3L2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (13): SBK3 (Two-hybrid), SBK3 (Two-hybrid), SBK3 (Two-hybrid), SBK3 (Two-hybrid), SBK3 (Two-hybrid), SBK3 (Two-hybrid), SBK3 (Two-hybrid), SBK3 (Two-hybrid), SBK3 (Two-hybrid), SBK3 (Two-hybrid), SBK3 (Two-hybrid), SBK3 (Two-hybrid), SBK3 (Two-hybrid)

ESM2 similar proteins: A7E3N7, A8VU90, B1WBU5, D3KCC4, O95382, P08923, P0C263, P0C264, P0C5K0, P0C5K1, P54265, Q06418, Q09013, Q13470, Q14296, Q16671, Q28616, Q4FZD7, Q53GL7, Q58EX7, Q60806, Q62070, Q62893, Q643R3, Q6DT37, Q6F5E8, Q6NVG1, Q6P5Z2, Q6VY05, Q76MJ5, Q80UW5, Q8CIE4, Q8CJ00, Q8IYX4, Q8K045, Q8K592, Q8NAG6, Q8NCV1, Q95JV3, Q96LW2

Diamond homologs: A1A5Q6, A2XFF4, A7MB74, A8XJQ6, A8XW88, B1WAS2, B1WBU5, B8BBT7, C0HKC8, C0HKC9, G1X456, O61661, O70150, O88866, O94806, P00517, P05131, P05132, P05383, P05986, P06244, P06245, P0C263, P0C264, P0C5K0, P0C5K1, P0DP15, P12370, P16912, P17612, P21137, P22612, P22694, P25321, P27791, P34099, P36887, P45894, P57058, P57059

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	54
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

400 predictions. Top by Δscore:

Variant	Effect	Δscore
19:55544104:T:A	donor_gain	1.0000
19:55544794:CTCA:C	donor_loss	1.0000
19:55544795:TCA:T	donor_loss	1.0000
19:55544796:CA:C	donor_loss	1.0000
19:55544797:A:AC	donor_gain	1.0000
19:55544797:A:C	donor_loss	1.0000
19:55544797:AC:A	donor_gain	1.0000
19:55544797:ACC:A	donor_gain	1.0000
19:55544797:ACCC:A	donor_gain	1.0000
19:55544797:ACCCC:A	donor_gain	1.0000
19:55544798:C:CC	donor_gain	1.0000
19:55544798:CC:C	donor_gain	1.0000
19:55544798:CCC:C	donor_gain	1.0000
19:55544798:CCCC:C	donor_gain	1.0000
19:55544798:CCCCC:C	donor_gain	1.0000
19:55544801:C:A	donor_gain	1.0000
19:55544853:T:TA	donor_gain	1.0000
19:55541522:AGGCC:A	acceptor_gain	0.9900
19:55541523:GGCC:G	acceptor_gain	0.9900
19:55541524:GCC:G	acceptor_gain	0.9900
19:55541525:CC:C	acceptor_gain	0.9900
19:55541525:CCC:C	acceptor_gain	0.9900
19:55541526:CC:C	acceptor_gain	0.9900
19:55541527:C:CA	acceptor_loss	0.9900
19:55541527:C:CC	acceptor_gain	0.9900
19:55541527:C:T	acceptor_gain	0.9900
19:55541528:T:G	acceptor_loss	0.9900
19:55541534:C:CT	acceptor_gain	0.9900
19:55541535:A:T	acceptor_gain	0.9900
19:55544098:AC:A	donor_gain	0.9900

AlphaMissense

2279 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:55544283:C:A	K72N	0.998
19:55544283:C:G	K72N	0.998
19:55544285:T:C	K72E	0.996
19:55541377:G:C	D183E	0.993
19:55541377:G:T	D183E	0.993
19:55541435:A:T	V164D	0.993
19:55541045:C:A	R294M	0.992
19:55541378:T:A	D183V	0.992
19:55544284:T:A	K72M	0.992
19:55541202:A:G	W242R	0.991
19:55541202:A:T	W242R	0.991
19:55541432:T:A	K165I	0.991
19:55541200:C:A	W242C	0.990
19:55541200:C:G	W242C	0.990
19:55541378:T:C	D183G	0.990
19:55541378:T:G	D183A	0.990
19:55544151:G:C	F116L	0.990
19:55544151:G:T	F116L	0.990
19:55544153:A:G	F116L	0.990
19:55544235:G:C	F88L	0.990
19:55544235:G:T	F88L	0.990
19:55544237:A:G	F88L	0.990
19:55544247:G:C	F84L	0.990
19:55544247:G:T	F84L	0.990
19:55544249:A:G	F84L	0.990
19:55541250:A:G	W226R	0.989
19:55541250:A:T	W226R	0.989
19:55541420:A:T	V169E	0.989
19:55541447:A:T	V160D	0.989
19:55544284:T:G	K72T	0.989

dbSNP variants (sampled 300 via entrez): RS1000103830 (19:55540166 G>C), RS1000361849 (19:55546949 C>G,T), RS1000462783 (19:55544683 C>G,T), RS1000522810 (19:55544502 C>T), RS1002015009 (19:55544934 C>T), RS1002574880 (19:55541655 T>C), RS1002708572 (19:55547361 G>T), RS1002995269 (19:55545322 C>A), RS1003506770 (19:55540719 C>A,T), RS1003691073 (19:55546008 G>A), RS1003723622 (19:55545735 C>T), RS1003993081 (19:55540535 A>G), RS1004085369 (19:55541999 T>C), RS1004527805 (19:55540463 G>C), RS1004542960 (19:55546718 C>T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003927_2	Dysmenorrheic pain	5.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007889	dysmenorrheic pain measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5116 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

10 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 121,814 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL603469	LESTAURTINIB	3
CHEMBL1721885	SU-014813	2	363
CHEMBL475251	R-406	2	762
CHEMBL572878	TOZASERTIB	2	2,998
CHEMBL1908397	KW-2449	1	622

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — NKF1 family

ChEMBL bioactivities

19 potent at pChembl≥5 of 19 total, top 17 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.60	Kd	25	nM	STAUROSPORINE
7.27	Kd	54	nM	TAE-684
6.92	Kd	120	nM	LESTAURTINIB
6.72	Kd	190	nM	R-406
6.64	Kd	230	nM	KW-2449
6.62	Kd	240	nM	CRIZOTINIB
6.28	Kd	530	nM	TOZASERTIB
6.00	IC50	1000	nM	TP-030-1
6.00	IC50	1000	nM	TP-030-2
6.00	IC50	1000	nM	TP-030n
5.96	Kd	1100	nM	CHEMBL386051
5.96	Kd	1100	nM	CHEMBL1908395
5.72	Kd	1900	nM	SUNITINIB
5.70	Kd	2000	nM	NINTEDANIB
5.54	Kd	2900	nM	FEDRATINIB
5.30	Kd	5000	nM	SU-014813
5.24	Kd	5800	nM	RUXOLITINIB

PubChem BioAssay actives

16 with measured affinity, of 127 total; 14 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
(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	624747: Binding constant for SgK110 kinase domain	kd	0.0250	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	624747: Binding constant for SgK110 kinase domain	kd	0.0540	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	508084: Binding affinity to SgK110	kd	0.1200	uM
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one	624747: Binding constant for SgK110 kinase domain	kd	0.1900	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	624747: Binding constant for SgK110 kinase domain	kd	0.2300	uM
Crizotinib	624747: Binding constant for SgK110 kinase domain	kd	0.2400	uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	624747: Binding constant for SgK110 kinase domain	kd	0.5300	uM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide;hydrochloride	624747: Binding constant for SgK110 kinase domain	kd	1.1000	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	624747: Binding constant for SgK110 kinase domain	kd	1.1000	uM
Sunitinib	508084: Binding affinity to SgK110	kd	1.9000	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	624747: Binding constant for SgK110 kinase domain	kd	2.0000	uM
Fedratinib	624747: Binding constant for SgK110 kinase domain	kd	2.9000	uM
5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	624747: Binding constant for SgK110 kinase domain	kd	5.0000	uM
Ruxolitinib	624747: Binding constant for SgK110 kinase domain	kd	5.8000	uM

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	increases expression	1
coumarin	increases phosphorylation	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects response to substance	1
abrine	increases expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression	1
Smoke	increases expression	1
Testosterone	decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Cadmium Chloride	increases expression	1
Okadaic Acid	increases expression	1

ChEMBL screening assays

69 unique, capped per target: 69 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1017921	Binding	Inhibition of SgK110 assessed as enzyme activity relative to control	Examining the chirality, conformation and selective kinase inhibition of 3-((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile (CP-690,550). — J Med Chem

Clinical trials (associated diseases)

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