RSKR

Summary

RSKR (ribosomal protein S6 kinase related, HGNC:26314) is a protein-coding gene on chromosome 17q11.2, encoding Ribosomal protein S6 kinase-related protein (Q96LW2).

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

Source: NCBI Gene 124923 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 69 total
• MANE Select transcript: NM_001174103

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26314
Approved symbol	RSKR
Name	ribosomal protein S6 kinase related
Location	17q11.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ25006, SgK494
Ensembl gene	ENSG00000167524
Ensembl biotype	protein_coding
Entrez	124923

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 6 retained_intron, 3 protein_coding, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000301037, ENST00000461399, ENST00000469832, ENST00000481916, ENST00000494272, ENST00000526073, ENST00000527863, ENST00000527918, ENST00000530121, ENST00000577790, ENST00000579457, ENST00000581199, ENST00000584196, ENST00000871684

RefSeq mRNA: 1 — MANE Select: NM_001174103 NM_001174103

Canonical transcript exons

ENST00000301037 — 12 exons

Exon	Start	End
ENSE00001861685	28607963	28610699
ENSE00003463545	28612262	28612366
ENSE00003537419	28611143	28611253
ENSE00003540041	28611567	28611656
ENSE00003558188	28611768	28611795
ENSE00003564630	28612044	28612084
ENSE00003565529	28611393	28611481
ENSE00003609299	28612618	28612687
ENSE00003641933	28613078	28613146
ENSE00003903395	28614087	28614185
ENSE00004473835	28613262	28613345
ENSE00004475395	28613440	28613688

Expression profiles

Bgee: expression breadth ubiquitous, 237 present calls, max score 95.58.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5317 / max 57.4145, expressed in 84 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165042	0.5317	84

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	95.58	gold quality
cerebellar hemisphere	UBERON:0002245	94.78	gold quality
cerebellar cortex	UBERON:0002129	94.70	gold quality
left testis	UBERON:0004533	94.29	gold quality
right testis	UBERON:0004534	94.28	gold quality
cerebellum	UBERON:0002037	94.20	gold quality
primary visual cortex	UBERON:0002436	93.97	gold quality
buccal mucosa cell	CL:0002336	93.21	gold quality
right frontal lobe	UBERON:0002810	92.53	gold quality
nucleus accumbens	UBERON:0001882	91.66	gold quality
anterior cingulate cortex	UBERON:0009835	91.44	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.43	gold quality
occipital lobe	UBERON:0002021	91.26	gold quality
testis	UBERON:0000473	91.06	gold quality
hypothalamus	UBERON:0001898	89.62	gold quality
caudate nucleus	UBERON:0001873	89.43	gold quality
Brodmann (1909) area 23	UBERON:0013554	89.38	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	89.16	gold quality
tibial nerve	UBERON:0001323	88.74	gold quality
pituitary gland	UBERON:0000007	88.30	gold quality
adenohypophysis	UBERON:0002196	88.30	gold quality
adrenal tissue	UBERON:0018303	88.26	gold quality
putamen	UBERON:0001874	88.25	gold quality
right lobe of thyroid gland	UBERON:0001119	88.00	gold quality
left ovary	UBERON:0002119	87.68	gold quality
brain	UBERON:0000955	87.48	gold quality
neocortex	UBERON:0001950	87.27	gold quality
right ovary	UBERON:0002118	87.18	gold quality
forebrain	UBERON:0001890	87.03	gold quality
cortical plate	UBERON:0005343	87.01	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	4.49
E-ANND-3	yes	3.36

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• Discovered as a novel human kinase, classified within the AGC group and a novel RSKR (RSK-related) family. (PMID:12471243)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rskrb	ENSDARG00000086169
danio_rerio	rskra	ENSDARG00000087176
mus_musculus	Rskr	ENSMUSG00000037593
rattus_norvegicus	Rskr	ENSRNOG00000085070
caenorhabditis_elegans		WBGENE00017950

Paralogs (7): GRK3 (ENSG00000100077), GRK7 (ENSG00000114124), GRK4 (ENSG00000125388), GRK2 (ENSG00000173020), GRK1 (ENSG00000185974), GRK6 (ENSG00000198055), GRK5 (ENSG00000198873)

Protein

Protein identifiers

Ribosomal protein S6 kinase-related protein — Q96LW2 (reviewed: Q96LW2)

Alternative names: Sugen kinase 494

All UniProt accessions (4): A0A5H1ZRP1, E9PPC7, Q96LW2, J3KTE0

UniProt curated annotations — full annotation on UniProt →

Miscellaneous. May be due to an intron retention.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q96LW2-1	1	yes
Q96LW2-2	2
Q96LW2-3	3

RefSeq proteins (1): NP_001167574* (*=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
IPR045270	STKc_AGC	Domain

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): splice variant 4, binding site 2, chain 1, domain 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96LW2-F1	75.84	0.57

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): 229 (proton acceptor)

Ligand- & substrate-binding residues (2): 113–121; 136

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 56 (showing top): RRAGTTGT_UNKNOWN, chr17q11, DODD_NASOPHARYNGEAL_CARCINOMA_UP, PIT1_Q6, E4BP4_01, GOMF_PROTEIN_KINASE_ACTIVITY, NIKOLSKY_MUTATED_AND_AMPLIFIED_IN_BREAST_CANCER, GOMF_KINASE_ACTIVITY, EVI1_02, GOMF_PROTEIN_SERINE_THREONINE_KINASE_ACTIVITY, GOMF_ADENYL_NUCLEOTIDE_BINDING, GOMF_TRANSFERASE_ACTIVITY_TRANSFERRING_PHOSPHORUS_CONTAINING_GROUPS, TEF_Q6, FIGUEROA_AML_METHYLATION_CLUSTER_1_UP, FIGUEROA_AML_METHYLATION_CLUSTER_3_UP

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

GO Molecular Function (8): protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), 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
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1

Protein interactions and networks

STRING

778 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RSKR	CDRT15L2	A8MXV6	505
RSKR	TBC1D28	Q2M2D7	419
RSKR	CCDC144A	A2RUR9	408
RSKR	TMIGD1	Q6UXZ0	404
RSKR	SLC35G6	P0C7Q6	398
RSKR	SLC35G3	Q8N808	397
RSKR	MRM3	Q9HC36	389
RSKR	KRABD2	Q6ZNG9	386
RSKR	CHCT1	Q86WR6	379
RSKR	SPDYE4	A6NLX3	377
RSKR	OR3A2	P47893	376
RSKR	FNDC9	Q8TBE3	376
RSKR	A0A087WT91	A0A087WT91	370
RSKR	TBC1D26	Q86UD7	370
RSKR	TBC1D3G	Q6DHY5	367

IntAct

24 interactions, top by confidence:

A	B	Type	Score
RSKR	TRAPPC12	psi-mi:“MI:0915”(physical association)	0.560
VAC14	RSKR	psi-mi:“MI:0915”(physical association)	0.560
RSKR	ZNF581	psi-mi:“MI:0915”(physical association)	0.560
VENTX	RSKR	psi-mi:“MI:0915”(physical association)	0.560
TLX3	RSKR	psi-mi:“MI:0915”(physical association)	0.560
	RSKR	psi-mi:“MI:0915”(physical association)	0.560
SUOX	RSKR	psi-mi:“MI:0915”(physical association)	0.560
TRAPPC12	RSKR	psi-mi:“MI:0915”(physical association)	0.560
CANX	NACA	psi-mi:“MI:2364”(proximity)	0.270
PSTPIP1	RSKR	psi-mi:“MI:0915”(physical association)	0.000
RSKR	VAC14	psi-mi:“MI:0915”(physical association)	0.000
	RSKR	psi-mi:“MI:0915”(physical association)	0.000
RSKR	ZNF581	psi-mi:“MI:0915”(physical association)	0.000
VENTX	RSKR	psi-mi:“MI:0915”(physical association)	0.000
TLX3	RSKR	psi-mi:“MI:0915”(physical association)	0.000
SUOX	RSKR	psi-mi:“MI:0915”(physical association)	0.000

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: A1Z9X0, A2CI34, A2CI35, A8KBH6, A8XW88, F1M7Y5, O70146, P00542, P00543, P04409, P05126, P05128, P05129, P05696, P05771, P05772, P07332, P09215, P0CD62, P10102, P10829, P13678, P14238, P16054, P16879, P17252, P20444, P21137, P22612, P23298, P24723, P28867, P32866, P41743, P43057, P48562, P50527, P57078, P63318, P63319

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	56
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

12629 predictions. Top by Δscore:

Variant	Effect	Δscore
17:28473810:GTAAG:G	donor_gain	1.0000
17:28473813:AGGT:A	donor_loss	1.0000
17:28473814:GGTA:G	donor_loss	1.0000
17:28473815:GTAAG:G	donor_loss	1.0000
17:28489210:GCAG:G	acceptor_loss	1.0000
17:28489211:CAG:C	acceptor_loss	1.0000
17:28489211:CAGG:C	acceptor_gain	1.0000
17:28489212:AGGA:A	acceptor_gain	1.0000
17:28489213:GGAG:G	acceptor_gain	1.0000
17:28489343:G:GA	donor_loss	1.0000
17:28490873:G:GT	donor_gain	1.0000
17:28490891:G:GT	donor_gain	1.0000
17:28490902:GCTTG:G	donor_gain	1.0000
17:28490903:C:G	donor_gain	1.0000
17:28490904:TTGGT:T	donor_loss	1.0000
17:28490908:T:A	donor_loss	1.0000
17:28491614:ACTC:A	donor_gain	1.0000
17:28491615:CTC:C	donor_gain	1.0000
17:28491616:TC:T	donor_gain	1.0000
17:28491618:G:GG	donor_gain	1.0000
17:28491724:CTTCA:C	acceptor_loss	1.0000
17:28491725:TTCAG:T	acceptor_loss	1.0000
17:28491726:TCAG:T	acceptor_loss	1.0000
17:28491727:CAGGC:C	acceptor_loss	1.0000
17:28491728:A:AG	acceptor_gain	1.0000
17:28491728:A:C	acceptor_loss	1.0000
17:28491728:AG:A	acceptor_gain	1.0000
17:28491729:G:GC	acceptor_gain	1.0000
17:28491729:GG:G	acceptor_gain	1.0000
17:28491729:GGC:G	acceptor_gain	1.0000

AlphaMissense

2674 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:28613476:A:C	F96L	0.981
17:28613476:A:T	F96L	0.981
17:28613478:A:G	F96L	0.981
17:28613262:C:A	K136N	0.977
17:28613262:C:G	K136N	0.977
17:28613096:T:A	K153N	0.967
17:28613096:T:G	K153N	0.967
17:28611434:A:G	W287R	0.965
17:28611434:A:T	W287R	0.965
17:28611637:G:C	D247E	0.965
17:28611637:G:T	D247E	0.965
17:28612622:G:C	F181L	0.962
17:28612622:G:T	F181L	0.962
17:28612624:A:G	F181L	0.962
17:28612044:C:A	K231N	0.961
17:28612044:C:G	K231N	0.961
17:28613305:A:G	L122P	0.953
17:28613477:A:G	F96S	0.953
17:28612050:A:C	D229E	0.952
17:28612050:A:T	D229E	0.952
17:28613316:A:C	F118L	0.952
17:28613316:A:T	F118L	0.952
17:28613318:A:G	F118L	0.952
17:28613135:C:A	K140N	0.951
17:28613135:C:G	K140N	0.951
17:28613488:A:C	F92L	0.946
17:28613488:A:T	F92L	0.946
17:28613490:A:G	F92L	0.946
17:28611634:A:C	F248L	0.945
17:28611634:A:T	F248L	0.945

dbSNP variants (sampled 300 via entrez): RS1000450802 (17:28609748 A>G), RS1000479887 (17:28610299 C>T), RS1000783666 (17:28608092 A>C), RS1000974955 (17:28614946 C>A,G,T), RS1001345139 (17:28614690 G>A), RS1001673267 (17:28610823 G>C), RS1002304941 (17:28608972 G>A), RS1003029729 (17:28607576 C>G), RS1003283519 (17:28614577 C>G), RS1004249916 (17:28609341 C>G), RS1004818558 (17:28614561 C>G), RS1005191325 (17:28614224 C>T), RS1005256887 (17:28610879 G>A), RS1005783873 (17:28613591 A>T), RS1007008216 (17:28613930 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

0 associations (top):

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 — RSKR subfamily

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, decreases methylation	5
sodium arsenite	affects cotreatment, increases abundance, increases expression, decreases expression	2
mercuric bromide	affects cotreatment, decreases expression	2
Benzo(a)pyrene	affects methylation, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Leflunomide	decreases expression	1
Arsenic	decreases expression, affects cotreatment, increases abundance, increases expression	1
Demecolcine	decreases expression	1
Estradiol	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Dronabinol	increases methylation	1
Thiram	decreases expression	1
Urethane	increases expression	1
Vanadates	decreases expression	1
Vincristine	decreases expression	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	decreases expression	1
Okadaic Acid	increases expression	1
Copper Sulfate	increases expression	1
Lactic Acid	increases expression	1
Acrylamide	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TK91	HAP1 SGK494 (-) 1	Cancer cell line	Male
CVCL_TK92	HAP1 SGK494 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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