RPS6KL1

Summary

RPS6KL1 (ribosomal protein S6 kinase like 1, HGNC:20222) is a protein-coding gene on chromosome 14q24.2, encoding Ribosomal protein S6 kinase-like 1 (Q9Y6S9).

Predicted to enable ATP binding activity; protein serine kinase activity; and protein serine/threonine kinase activity. Predicted to be involved in chromatin remodeling. Predicted to be located in ribosome. Predicted to be part of ribonucleoprotein complex.

Source: NCBI Gene 83694 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 109 total
• MANE Select transcript: NM_031464

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20222
Approved symbol	RPS6KL1
Name	ribosomal protein S6 kinase like 1
Location	14q24.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC11287, RSKL2
Ensembl gene	ENSG00000198208
Ensembl biotype	protein_coding
Entrez	83694

Gene structure

Transcript identifiers

Ensembl transcripts: 45 — 37 protein_coding, 6 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000354625, ENST00000553315, ENST00000553646, ENST00000553789, ENST00000553894, ENST00000553971, ENST00000554834, ENST00000554900, ENST00000555009, ENST00000555647, ENST00000555834, ENST00000555910, ENST00000556776, ENST00000556848, ENST00000557383, ENST00000557413, ENST00000906484, ENST00000906485, ENST00000906486, ENST00000920809, ENST00000920810, ENST00000920811, ENST00000920812, ENST00000920813, ENST00000920814, ENST00000920815, ENST00000920816, ENST00000920817, ENST00000961446, ENST00000961447, ENST00000961448, ENST00000961449, ENST00000961450, ENST00000961451, ENST00000961452, ENST00000961453, ENST00000961454, ENST00000961455, ENST00000961456, ENST00000961457, ENST00000961458, ENST00000961459, ENST00000961460, ENST00000961461, ENST00000961462

RefSeq mRNA: 7 — MANE Select: NM_031464 NM_001370252, NM_001370253, NM_001370255, NM_001370256, NM_001370257, NM_001370258, NM_031464

CCDS: CCDS9834

Canonical transcript exons

ENST00000557413 — 12 exons

Exon	Start	End
ENSE00000808278	74907435	74907530
ENSE00001195951	74909543	74910148
ENSE00001384618	74909101	74909190
ENSE00001644738	74903951	74907124
ENSE00002434082	74921978	74922485
ENSE00002505136	74923180	74923260
ENSE00003477978	74918513	74918605
ENSE00003506074	74919845	74919969
ENSE00003565790	74911248	74911380
ENSE00003585643	74911794	74911841
ENSE00003613925	74908850	74908932
ENSE00003684114	74921277	74921561

Expression profiles

Bgee: expression breadth ubiquitous, 183 present calls, max score 93.81.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.6277 / max 76.3954, expressed in 919 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
144089	2.6204	798
144090	0.8471	405
144088	0.1602	85

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	93.81	gold quality
right frontal lobe	UBERON:0002810	93.29	gold quality
cortical plate	UBERON:0005343	93.28	gold quality
cerebellar hemisphere	UBERON:0002245	92.94	gold quality
cerebellar cortex	UBERON:0002129	92.87	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.10	gold quality
prefrontal cortex	UBERON:0000451	91.55	gold quality
cerebellum	UBERON:0002037	91.38	gold quality
anterior cingulate cortex	UBERON:0009835	91.25	gold quality
apex of heart	UBERON:0002098	90.64	gold quality
frontal cortex	UBERON:0001870	89.56	gold quality
neocortex	UBERON:0001950	89.41	gold quality
pancreatic ductal cell	CL:0002079	89.13	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	88.79	gold quality
hypothalamus	UBERON:0001898	88.33	gold quality
adenohypophysis	UBERON:0002196	88.03	gold quality
pituitary gland	UBERON:0000007	87.87	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	87.74	gold quality
gastrocnemius	UBERON:0001388	87.67	gold quality
amygdala	UBERON:0001876	87.66	gold quality
putamen	UBERON:0001874	87.58	gold quality
cerebral cortex	UBERON:0000956	87.50	gold quality
caudate nucleus	UBERON:0001873	86.95	gold quality
nucleus accumbens	UBERON:0001882	86.72	gold quality
brain	UBERON:0000955	86.69	gold quality
muscle of leg	UBERON:0001383	86.66	gold quality
forebrain	UBERON:0001890	86.65	gold quality
spinal cord	UBERON:0002240	85.41	gold quality
Ammon’s horn	UBERON:0001954	85.23	gold quality
substantia nigra	UBERON:0002038	84.90	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.59

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• Identified as a pseudokinase and named RSKL2. (PMID:12471243)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rps6kl1	ENSDARG00000079024
mus_musculus	Rps6kl1	ENSMUSG00000019235
rattus_norvegicus	Rps6kl1	ENSRNOG00000005530
drosophila_melanogaster	CG7156	FBGN0038588
caenorhabditis_elegans		WBGENE00010096

Paralogs (2): SNX15 (ENSG00000110025), RPS6KC1 (ENSG00000136643)

Protein

Protein identifiers

Ribosomal protein S6 kinase-like 1 — Q9Y6S9 (reviewed: Q9Y6S9)

All UniProt accessions (6): A0A0G2JL89, Q9Y6S9, H0YJ58, H0YJ80, H0YJB8, H0YJR0

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. S6 kinase subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9Y6S9-1	1	yes
Q9Y6S9-2	2
Q9Y6S9-4	4

RefSeq proteins (7): NP_001357181, NP_001357182, NP_001357184, NP_001357185, NP_001357186, NP_001357187, NP_113652* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR007330	MIT_dom	Domain
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR035053	STK_RPK118-like	Domain
IPR036181	MIT_dom_sf	Homologous_superfamily
IPR051866	Intracell_Sig-Traffick_Protein	Family

Pfam: PF00069, PF04212

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 (16 total): splice variant 4, sequence variant 3, domain 2, region of interest 2, binding site 2, chain 1, sequence conflict 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y6S9-F1	68.92	0.33

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): 412 (proton acceptor)

Ligand- & substrate-binding residues (2): 151–159; 177

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 85 (showing top): chr14q24, AAAGACA_MIR511, HAND1E47_01, GOCC_RIBOSOME, GOCC_RIBONUCLEOPROTEIN_COMPLEX, GOMF_PROTEIN_KINASE_ACTIVITY, GOMF_KINASE_ACTIVITY, GOMF_PROTEIN_SERINE_THREONINE_KINASE_ACTIVITY, GOMF_ADENYL_NUCLEOTIDE_BINDING, GOMF_TRANSFERASE_ACTIVITY_TRANSFERRING_PHOSPHORUS_CONTAINING_GROUPS, LI_INDUCED_T_TO_NATURAL_KILLER_DN, NFY_Q6_01, LIM_MAMMARY_LUMINAL_PROGENITOR_UP, MODULE_426, CBX5_TARGET_GENES

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 (2): ribosome (GO:0005840), ribonucleoprotein complex (GO:1990904)

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
intracellular membraneless organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

656 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPS6KL1	ZNF524	Q96C55	711
RPS6KL1	ZNF710	Q8N1W2	667
RPS6KL1	ZNF541	Q9H0D2	667
RPS6KL1	ZC2HC1C	Q53FD0	544
RPS6KL1	PROX2	Q3B8N5	518
RPS6KL1	HEATR4	Q86WZ0	496
RPS6KL1	FREM3	P0C091	475
RPS6KL1	SNRPN	P14648	475
RPS6KL1	ARL14	Q8N4G2	474
RPS6KL1	AREL1	O15033	474
RPS6KL1	POLD1	P28340	461
RPS6KL1	RSPH9	Q9H1X1	440
RPS6KL1	YLPM1	P49750	437
RPS6KL1	MLH3	P49751	436
RPS6KL1	INPP4B	O15327	414

IntAct

4 interactions, top by confidence:

A	B	Type	Score
RPS6KL1	MED30	psi-mi:“MI:0915”(physical association)	0.500
RPS6KL1	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.400
RPS6KL1	GOLIM4	psi-mi:“MI:0914”(association)	0.350
RPS6KL1	TYMP	psi-mi:“MI:0914”(association)	0.350

BioGRID (51): RPS6KL1 (Affinity Capture-RNA), RPS6KL1 (Affinity Capture-RNA), CRABP2 (Affinity Capture-MS), MED30 (Affinity Capture-MS), TYMP (Affinity Capture-MS), ABCF3 (Affinity Capture-MS), ALDH1A3 (Affinity Capture-MS), GOLIM4 (Affinity Capture-MS), NDUFA4 (Affinity Capture-MS), SEC16A (Affinity Capture-MS), POLR1C (Affinity Capture-MS), RBFOX2 (Affinity Capture-MS), ERLIN1 (Affinity Capture-MS), UBR5 (Affinity Capture-MS), ASMTL (Affinity Capture-MS)

ESM2 similar proteins: A1E2V0, A2AWP0, A6QPT6, A9JTP3, A9ULZ2, B1WBS3, O08863, O14771, O15037, O43918, O94966, P05433, P48778, P51617, Q08DD7, Q0P5G1, Q13077, Q15477, Q2LGB3, Q3TD16, Q3UJD6, Q499Z3, Q4R3B7, Q4R6Y5, Q5RA67, Q5XIS1, Q62210, Q62406, Q6AXX1, Q6J1Y9, Q75NR7, Q80U38, Q80VL3, Q811H0, Q8BHW9, Q8CFK6, Q8JHV9, Q8K330, Q8R2S1, Q8TE77

Diamond homologs: Q148E7, Q3UR97, Q4V896, Q5RA67, Q8BLK9, Q8R2S1, Q91WE1, Q96S38, Q9C0U7, Q9NRS6, Q9Y6S9, D3ZHP7, Q5AG40, Q6PHR2, A1Z9X0, A8KBH6, A8XNJ6, G1X456, J9W0G9, M3TYT0, O19111, O70293, O75116, O75582, O75676, P04409, P05126, P05128, P05129, P05696, P05771, P05772, P05986, P06244, P06245, P09217, P10102, P10665, P10666, P10829

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	90
Likely benign	11
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1755 predictions. Top by Δscore:

Variant	Effect	Δscore
14:74909194:CAGTG:C	acceptor_gain	1.0000
14:74909195:A:T	acceptor_gain	1.0000
14:74909196:G:GC	acceptor_gain	1.0000
14:74909198:G:GC	acceptor_gain	1.0000
14:74909200:G:GC	acceptor_gain	1.0000
14:74919844:CCGCG:C	donor_gain	1.0000
14:74919965:GTCAA:G	acceptor_gain	1.0000
14:74919966:TCAA:T	acceptor_gain	1.0000
14:74919967:CAA:C	acceptor_gain	1.0000
14:74919967:CAAC:C	acceptor_gain	1.0000
14:74919968:AA:A	acceptor_gain	1.0000
14:74919968:AAC:A	acceptor_loss	1.0000
14:74919969:ACTG:A	acceptor_loss	1.0000
14:74919970:C:CA	acceptor_loss	1.0000
14:74919970:C:CC	acceptor_gain	1.0000
14:74919971:T:C	acceptor_loss	1.0000
14:74921271:CCTCA:C	donor_loss	1.0000
14:74921272:CTCA:C	donor_loss	1.0000
14:74921273:TCA:T	donor_loss	1.0000
14:74921274:CACCG:C	donor_loss	1.0000
14:74921275:A:AC	donor_gain	1.0000
14:74921275:A:C	donor_loss	1.0000
14:74921275:AC:A	donor_gain	1.0000
14:74921276:C:CC	donor_gain	1.0000
14:74921276:C:CG	donor_loss	1.0000
14:74921276:CC:C	donor_gain	1.0000
14:74908928:CACCT:C	acceptor_gain	0.9900
14:74909193:CCAG:C	acceptor_gain	0.9900
14:74909196:G:C	acceptor_gain	0.9900
14:74909200:G:C	acceptor_gain	0.9900

AlphaMissense

3527 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:74908886:G:C	S469R	0.994
14:74908886:G:T	S469R	0.994
14:74908888:T:G	S469R	0.994
14:74908891:A:G	W468R	0.994
14:74908891:A:T	W468R	0.994
14:74908882:C:A	G471W	0.992
14:74921316:A:C	Y76D	0.992
14:74908889:C:A	W468C	0.991
14:74908889:C:G	W468C	0.991
14:74909161:A:G	W434R	0.991
14:74909161:A:T	W434R	0.991
14:74919915:A:G	L107P	0.991
14:74919919:A:C	Y106D	0.991
14:74921294:A:G	L83P	0.991
14:74921323:G:C	F73L	0.991
14:74921323:G:T	F73L	0.991
14:74921325:A:G	F73L	0.991
14:74921372:A:G	I57T	0.991
14:74908881:C:T	G471E	0.990
14:74919907:C:G	A110P	0.990
14:74921327:G:T	A72D	0.990
14:74921306:C:T	G79D	0.989
14:74907034:A:G	W544R	0.988
14:74907034:A:T	W544R	0.988
14:74907123:A:G	L514P	0.988
14:74911262:A:G	L217P	0.988
14:74911268:A:G	L215P	0.988
14:74911831:A:T	V165D	0.988
14:74921363:G:T	A60D	0.988
14:74921372:A:C	I57S	0.988

dbSNP variants (sampled 300 via entrez): RS1000172409 (14:74912338 G>A), RS1000336096 (14:74914735 G>A), RS1000398446 (14:74906650 G>A,C), RS1000629554 (14:74908592 A>C,G), RS1000650494 (14:74905494 C>T), RS1000684937 (14:74905616 C>A), RS1000769495 (14:74906427 G>A,T), RS1000793564 (14:74913505 T>C), RS1000950144 (14:74922954 G>C), RS1000958056 (14:74910915 A>C,G), RS1000997630 (14:74919272 G>T), RS1001037418 (14:74917144 T>C), RS1001039947 (14:74907781 C>T), RS1001199714 (14:74904749 G>A), RS1001240417 (14:74919134 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

6 associations (top):

Study	Trait	p-value
GCST005237_3	Mood instability	1.000000e-06
GCST005238_3	Mood instability	3.000000e-09
GCST005839_15	Depression	4.000000e-09
GCST009325_17	Parkinson’s disease or first degree relation to individual with Parkinson’s disease	2.000000e-09
GCST009600_51	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	2.000000e-08
GCST010242_42	HDL cholesterol levels	6.000000e-15

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008475	mood instability measurement
EFO:0004612	high density lipoprotein cholesterol 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 — RSKL family

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation	2
pirinixic acid	affects binding, increases activity, increases expression	1
beta-lapachone	increases expression	1
afimoxifene	decreases response to substance	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	increases expression	1
tebuconazole	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Air Pollutants	increases abundance, increases expression	1
Doxorubicin	decreases expression	1
Lead	affects splicing	1
Oxygen	decreases expression	1
Silicon Dioxide	increases expression	1
Smoke	decreases expression	1
Testosterone	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	increases methylation	1
Sodium Selenite	decreases expression	1
Okadaic Acid	affects expression	1
Acrylamide	decreases expression	1
Particulate Matter	increases expression, increases abundance	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TJ73	HAP1 RPS6KL1 (-) 1	Cancer cell line	Male
CVCL_TJ74	HAP1 RPS6KL1 (-) 2	Cancer cell line	Male
CVCL_TJ75	HAP1 RPS6KL1 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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