SBK2

Summary

SBK2 (SH3 domain binding kinase family member 2, HGNC:34416) is a protein-coding gene on chromosome 19q13.42, encoding Serine/threonine-protein kinase SBK2 (P0C263).

Predicted to enable MAP kinase kinase activity. Predicted to be involved in MAPK cascade.

Source: NCBI Gene 646643 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 82 total
• MANE Select transcript: NM_001370096

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:34416
Approved symbol	SBK2
Name	SH3 domain binding kinase family member 2
Location	19q13.42
Locus type	gene with protein product
Status	Approved
Aliases	SGK069
Ensembl gene	ENSG00000187550
Ensembl biotype	protein_coding
OMIM	620414
Entrez	646643

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000344158, ENST00000413299, ENST00000912390, ENST00000964147

RefSeq mRNA: 1 — MANE Select: NM_001370096 NM_001370096

CCDS: CCDS42631

Canonical transcript exons

ENST00000413299 — 4 exons

Exon	Start	End
ENSE00000000244	55528611	55530323
ENSE00001381781	55531143	55531345
ENSE00001680848	55537054	55537133
ENSE00001688978	55536042	55536296

Expression profiles

Bgee: expression breadth broad, 50 present calls, max score 97.21.

FANTOM5 (CAGE): breadth broad, TPM avg 1.0558 / max 265.5003, expressed in 207 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
182833	0.6209	118
182835	0.3898	151
182834	0.0377	15
182831	0.0055	3
182832	0.0019	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right atrium auricular region	UBERON:0006631	97.21	gold quality
apex of heart	UBERON:0002098	77.99	gold quality
hindlimb stylopod muscle	UBERON:0004252	72.95	gold quality
heart	UBERON:0000948	72.00	gold quality
heart left ventricle	UBERON:0002084	68.19	gold quality
gastrocnemius	UBERON:0001388	61.45	gold quality
islet of Langerhans	UBERON:0000006	60.51	gold quality
muscle of leg	UBERON:0001383	59.99	gold quality
skeletal muscle tissue	UBERON:0001134	59.76	gold quality
muscle tissue	UBERON:0002385	54.97	gold quality
right testis	UBERON:0004534	52.86	gold quality
left testis	UBERON:0004533	52.72	gold quality
testis	UBERON:0000473	51.87	gold quality
omental fat pad	UBERON:0010414	49.71	gold quality
cerebellum	UBERON:0002037	47.85	silver quality
cerebellar cortex	UBERON:0002129	47.69	silver quality
cerebellar hemisphere	UBERON:0002245	47.62	silver quality
right hemisphere of cerebellum	UBERON:0014890	46.94	silver quality
pancreas	UBERON:0001264	45.41	gold quality
adipose tissue	UBERON:0001013	42.04	gold quality
colonic epithelium	UBERON:0000397	41.30	gold quality
bone marrow cell	CL:0002092	40.62	gold quality
blood	UBERON:0000178	40.35	silver quality
cortical plate	UBERON:0005343	40.34	gold quality
myometrium	UBERON:0001296	39.94	gold quality
bone marrow	UBERON:0002371	39.87	gold quality
primary visual cortex	UBERON:0002436	39.05	gold quality
placenta	UBERON:0001987	37.82	silver quality
body of uterus	UBERON:0009853	37.58	gold quality
duodenum	UBERON:0002114	37.44	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.82

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• Better known as SgK069. Contains predicted active kinase domain, classified into the NKF1 metazoan-specific family of kinases. “Bsk146” is an obsolete term for it’s paralog, SBK1. (PMID:12471243)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Sbk2	ENSMUSG00000030433
rattus_norvegicus	Sbk2	ENSRNOG00000038625

Paralogs (35): MAP3K14 (ENSG00000006062), MAP4K3 (ENSG00000011566), MAP4K5 (ENSG00000012983), MAP2K3 (ENSG00000034152), SLK (ENSG00000065613), MAP4K4 (ENSG00000071054), STK10 (ENSG00000072786), PAK3 (ENSG00000077264), STRADB (ENSG00000082146), MAP3K1 (ENSG00000095015), STK4 (ENSG00000101109), PAK5 (ENSG00000101349), STK24 (ENSG00000102572), STK3 (ENSG00000104375), MAP4K1 (ENSG00000104814), MAP3K8 (ENSG00000107968), MAP2K6 (ENSG00000108984), NEK4 (ENSG00000114904), STK25 (ENSG00000115694), NRK (ENSG00000123572), PAK4 (ENSG00000130669), STK26 (ENSG00000134602), TAOK3 (ENSG00000135090), PAK6 (ENSG00000137843), MINK1 (ENSG00000141503), PAK1 (ENSG00000149269), TAOK2 (ENSG00000149930), TNIK (ENSG00000154310), TAOK1 (ENSG00000160551), MAP4K2 (ENSG00000168067), OXSR1 (ENSG00000172939), MAP3K19 (ENSG00000176601), PAK2 (ENSG00000180370), STK39 (ENSG00000198648), STRADA (ENSG00000266173)

Protein

Protein identifiers

Serine/threonine-protein kinase SBK2 — P0C263 (reviewed: P0C263)

Alternative names: SH3 domain-binding kinase family member 2, Sugen kinase 69

All UniProt accessions (1): P0C263

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_001357025* (*=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 (9 total): sequence variant 3, binding site 2, chain 1, domain 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0C263-F1	90.25	0.85

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): 183 (proton acceptor)

Ligand- & substrate-binding residues (2): 68–76; 91

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 18 (showing top): GOMF_PROTEIN_KINASE_ACTIVITY, GOMF_KINASE_ACTIVITY, GOMF_PROTEIN_SERINE_THREONINE_KINASE_ACTIVITY, GOMF_MAP_KINASE_KINASE_ACTIVITY, GOMF_ADENYL_NUCLEOTIDE_BINDING, GOMF_TRANSFERASE_ACTIVITY_TRANSFERRING_PHOSPHORUS_CONTAINING_GROUPS, MARTENS_TRETINOIN_RESPONSE_UP, GOBP_MAPK_CASCADE, GOMF_PROTEIN_SERINE_KINASE_ACTIVITY, ZNF134_TARGET_GENES, LIU_OVARIAN_CANCER_TUMORS_AND_XENOGRAFTS_XDGS_UP, HE_LIM_SUN_FETAL_LUNG_C0_MID_MESOTHELIAL_CELL, GOMF_PURINE_NUCLEOTIDE_BINDING, chr19q13, GOMF_PROTEIN_SERINE_THREONINE_TYROSINE_KINASE_ACTIVITY

GO Biological Process (2): MAPK cascade (GO:0000165), protein phosphorylation (GO:0006468)

GO Molecular Function (8): protein serine/threonine kinase activity (GO:0004674), MAP kinase kinase activity (GO:0004708), ATP binding (GO:0005524), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), 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
intracellular signaling cassette	1
phosphorylation	1
protein modification process	1
MAPK cascade	1
protein serine/threonine/tyrosine kinase activity	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
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1

Protein interactions and networks

STRING

416 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SBK2	PTPRM	P28827	621
SBK2	TEDDM1	Q5T9Z0	566
SBK2	DCUN1D5	Q9BTE7	525
SBK2	STKLD1	Q8NE28	479
SBK2	FAM81A	Q8TBF8	437
SBK2	FBXW10B	O95170	424
SBK2	OR10P1	Q8NGE3	419
SBK2	SRPK3	Q9UPE1	406
SBK2	PRR32	B1ATL7	393
SBK2	PROCA1	Q8NCQ7	388
SBK2	TTLL9	Q3SXZ7	384
SBK2	RD3L	P0DJH9	378
SBK2	ADCK5	Q3MIX3	366
SBK2	PRR14	Q9BWN1	366
SBK2	QTMAN	Q4AE62	365

IntAct

2 interactions, top by confidence:

A	B	Type	Score
SBK2	HSP90AA1	psi-mi:“MI:0914”(association)	0.350

BioGRID (6): HSP90AA1 (Affinity Capture-MS), HSP90AB1 (Affinity Capture-MS), DDOST (Affinity Capture-MS), CDC37 (Affinity Capture-MS), MAVS (Affinity Capture-MS), TMPRSS11E (Affinity Capture-MS)

ESM2 similar proteins: A0A061IR73, A5YM72, A6QR56, A8MXQ7, D3KCC4, D3Z7H8, I3L5V6, O19179, O95382, P0C263, P0DPD7, P0DPE1, P10938, P11086, P14061, P51656, P51657, P51840, P52785, P54777, Q02846, Q0V8J4, Q13608, Q1WNP0, Q2VPK5, Q561R2, Q5XIH9, Q643R3, Q6NVG1, Q6PAT0, Q6SZW1, Q6ZPS2, Q7TMC8, Q8IYX4, Q8IZ83, Q8IZY2, Q8K248, Q8N0W3, Q8N2G8, Q96EY9

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	76
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

387 predictions. Top by Δscore:

Variant	Effect	Δscore
19:55531140:CA:C	donor_loss	1.0000
19:55531141:ACCTT:A	donor_loss	1.0000
19:55531295:C:CT	acceptor_gain	1.0000
19:55536038:GTACC:G	donor_loss	1.0000
19:55536039:TACC:T	donor_loss	1.0000
19:55536041:C:CT	donor_loss	1.0000
19:55536041:CCTTT:C	donor_gain	1.0000
19:55536104:T:TA	donor_gain	1.0000
19:55530319:CCCAC:C	acceptor_gain	0.9900
19:55530320:CCACC:C	acceptor_gain	0.9900
19:55530321:CAC:C	acceptor_gain	0.9900
19:55530322:AC:A	acceptor_gain	0.9900
19:55530322:ACCT:A	acceptor_loss	0.9900
19:55530323:CC:C	acceptor_gain	0.9900
19:55530324:C:CA	acceptor_loss	0.9900
19:55530325:T:G	acceptor_loss	0.9900
19:55531141:A:AC	donor_gain	0.9900
19:55531142:C:CC	donor_gain	0.9900
19:55531295:C:T	acceptor_gain	0.9900
19:55531306:G:C	acceptor_gain	0.9900
19:55536040:A:AC	donor_gain	0.9900
19:55536041:C:CC	donor_gain	0.9900
19:55536041:CCT:C	donor_gain	0.9900
19:55530320:CCAC:C	acceptor_gain	0.9800
19:55530321:CACC:C	acceptor_gain	0.9800
19:55530327:C:CT	acceptor_gain	0.9800
19:55531138:CGCA:C	donor_gain	0.9800
19:55536040:AC:A	donor_gain	0.9800
19:55536041:CC:C	donor_gain	0.9800
19:55536105:C:A	donor_gain	0.9800

AlphaMissense

2201 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:55531326:C:A	K91N	0.996
19:55531326:C:G	K91N	0.996
19:55529836:C:A	R315M	0.992
19:55529991:C:A	W263C	0.991
19:55529991:C:G	W263C	0.991
19:55530225:C:A	K185N	0.990
19:55530225:C:G	K185N	0.990
19:55529993:A:G	W263R	0.989
19:55529993:A:T	W263R	0.989
19:55530018:G:C	F254L	0.989
19:55530018:G:T	F254L	0.989
19:55530020:A:G	F254L	0.989
19:55530171:G:C	D203E	0.988
19:55530171:G:T	D203E	0.988
19:55531290:G:C	F103L	0.988
19:55531290:G:T	F103L	0.988
19:55531292:A:G	F103L	0.988
19:55530172:T:A	D203V	0.987
19:55529835:C:A	R315S	0.984
19:55529835:C:G	R315S	0.984
19:55529995:G:T	P262H	0.983
19:55530046:T:A	D245V	0.982
19:55530232:T:A	D183V	0.982
19:55529836:C:G	R315T	0.981
19:55530047:C:G	D245H	0.981
19:55530214:A:T	V189D	0.981
19:55530004:C:A	G259V	0.978
19:55530039:C:A	W247C	0.978
19:55530039:C:G	W247C	0.978
19:55536059:A:T	V79D	0.978

dbSNP variants (sampled 300 via entrez): RS1000427906 (19:55529955 C>A,G,T), RS1000806750 (19:55536400 C>T), RS1001265594 (19:55530304 G>A,C), RS1001283178 (19:55533296 A>G), RS1001586997 (19:55533528 C>T), RS1001881880 (19:55539079 C>T), RS1002299978 (19:55529009 C>G,T), RS1002324927 (19:55535071 G>A), RS1002352906 (19:55534563 C>G,T), RS1002481495 (19:55537498 G>C), RS1002963430 (19:55534650 T>G), RS1002991238 (19:55537004 C>T), RS1003021855 (19:55536864 C>A), RS1003095275 (19:55536664 C>G,T), RS1003250106 (19:55529242 A>G,T)

Disease associations

OMIM: gene MIM:620414 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003927_2	Dysmenorrheic pain	5.000000e-07
GCST004744_3	Lung adenocarcinoma	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007889	dysmenorrheic pain measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — NKF1 family

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Arsenic	affects methylation, decreases expression	2
aristolochic acid I	increases expression	1
bisphenol A	decreases methylation	1
ethyl-p-hydroxybenzoate	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
abrine	increases expression	1
Sunitinib	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cadmium	increases expression	1
Endosulfan	increases expression	1
Smoke	increases expression	1
Triclosan	increases expression	1
Valproic Acid	increases methylation	1
1-Methyl-4-phenylpyridinium	increases expression	1

Clinical trials (associated diseases)

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