RPS6KC1

Summary

RPS6KC1 (ribosomal protein S6 kinase C1, HGNC:10439) is a protein-coding gene on chromosome 1q32.3, encoding Ribosomal protein S6 kinase delta-1 (Q96S38). May be involved in transmitting sphingosine-1 phosphate (SPP)-mediated signaling into the cell.

Sphingosine kinase catalyzes the formation of sphingosine 1 phosphate, a lipid cellular messenger. The protein encoded by this gene can bind to sphingosine kinase and to phosphatidylinositol 3-phosphate, suggesting a role in sphingosine 1 phophate signaling. The encoded protein can also bind to peroxiredoxin-3 and may help transport it to mitochondria.

Source: NCBI Gene 26750 — RefSeq curated summary.

At a glance

• Gene–disease (curated): periventricular leukomalacia (Limited, GenCC)
• GWAS associations: 5
• Clinical variants (ClinVar): 379 total — 5 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 45
• Druggable target: yes
• MANE Select transcript: NM_012424

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10439
Approved symbol	RPS6KC1
Name	ribosomal protein S6 kinase C1
Location	1q32.3
Locus type	gene with protein product
Status	Approved
Aliases	humS6PKh1, RSKL1
Ensembl gene	ENSG00000136643
Ensembl biotype	protein_coding
OMIM	617517
Entrez	26750

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 19 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000366959, ENST00000366960, ENST00000468069, ENST00000490299, ENST00000491616, ENST00000543354, ENST00000543470, ENST00000614059, ENST00000615329, ENST00000863048, ENST00000863049, ENST00000863050, ENST00000863051, ENST00000863052, ENST00000863053, ENST00000863054, ENST00000863055, ENST00000914115, ENST00000914116, ENST00000914117, ENST00000962851, ENST00000962852

RefSeq mRNA: 31 — MANE Select: NM_012424 NM_001136138, NM_001287218, NM_001287219, NM_001287220, NM_001287221, NM_001349646, NM_001349647, NM_001349648, NM_001349649, NM_001349650, NM_001349651, NM_001349652, NM_001349653, NM_001349654, NM_001349657, NM_001349658, NM_001349659, NM_001349660, NM_001349661, NM_001349662, NM_001349663, NM_001349664, NM_001349665, NM_001349666, NM_001349667, NM_001349668, NM_001349669, NM_001349670, NM_001349671, NM_001349672, NM_012424

CCDS: CCDS1513, CCDS44317, CCDS73028, CCDS73029, CCDS73030

Canonical transcript exons

ENST00000366960 — 15 exons

Exon	Start	End
ENSE00003465985	213261558	213261640
ENSE00003477515	213232123	213232255
ENSE00003477892	213129527	213129889
ENSE00003521253	213071006	213071041
ENSE00003529086	213117317	213117410
ENSE00003530968	213262721	213262816
ENSE00003581900	213230497	213230544
ENSE00003615623	213242569	213242658
ENSE00003622945	213077696	213077816
ENSE00003649106	213176400	213176492
ENSE00003687658	213240702	213242297
ENSE00003693172	213104454	213104569
ENSE00003750812	213167858	213167973
ENSE00003841579	213272524	213274774
ENSE00003843937	213051241	213051509

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 98.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.9937 / max 467.5189, expressed in 1818 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
8503	21.7340	1818
8504	0.2597	115

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	98.57	gold quality
male germ cell	CL:0000015	95.87	gold quality
calcaneal tendon	UBERON:0003701	90.16	gold quality
middle temporal gyrus	UBERON:0002771	89.63	gold quality
Brodmann (1909) area 23	UBERON:0013554	89.06	gold quality
secondary oocyte	CL:0000655	89.00	gold quality
adrenal tissue	UBERON:0018303	88.82	gold quality
cortical plate	UBERON:0005343	88.50	gold quality
tendon	UBERON:0000043	86.50	gold quality
prefrontal cortex	UBERON:0000451	86.28	gold quality
primary visual cortex	UBERON:0002436	86.15	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	85.91	gold quality
corpus callosum	UBERON:0002336	85.62	gold quality
monocyte	CL:0000576	85.50	gold quality
popliteal artery	UBERON:0002250	85.28	gold quality
tibial artery	UBERON:0007610	85.27	gold quality
superior frontal gyrus	UBERON:0002661	85.24	gold quality
frontal cortex	UBERON:0001870	85.19	gold quality
mononuclear cell	CL:0000842	85.10	gold quality
medial globus pallidus	UBERON:0002477	85.08	gold quality
postcentral gyrus	UBERON:0002581	85.04	gold quality
Brodmann (1909) area 9	UBERON:0013540	84.98	gold quality
neocortex	UBERON:0001950	84.92	gold quality
leukocyte	CL:0000738	84.90	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	84.70	gold quality
ganglionic eminence	UBERON:0004023	84.59	gold quality
cranial nerve II	UBERON:0000941	84.51	gold quality
spinal cord	UBERON:0002240	84.51	gold quality
right frontal lobe	UBERON:0002810	84.47	gold quality
cerebral cortex	UBERON:0000956	84.41	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.32

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

57 targeting RPS6KC1, 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-126-5P	100.00	72.71	3180
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-3659	99.70	67.97	694
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-4666B	99.64	68.69	1282
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-122B-5P	99.46	70.81	1457
HSA-MIR-516A-3P	99.46	67.96	1378
HSA-MIR-516B-3P	99.46	67.96	1378
HSA-MIR-7162-5P	99.46	68.08	1368
HSA-MIR-4273	99.45	67.93	1206
HSA-MIR-6165	99.44	67.12	1389

Literature-anchored findings (GeneRIF, showing 3)

• cloning and characterization of RPK118 as a sphingosine kinase-1-binding protein (PMID:12077123)
• Identified as a pseudokinase and named RSKL1 (PMID:12471243)
• findings indicate that RPK118 is a PRDX3-binding protein that may be involved in transporting PRDX3 from the cytoplasm to its mitochondrial site of function or to other membrane structures via endosome trafficking. (PMID:15750338)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rps6kc1	ENSDARG00000104103
mus_musculus	Rps6kc1	ENSMUSG00000089872
rattus_norvegicus	Rps6kc1	ENSRNOG00000003767

Paralogs (2): SNX15 (ENSG00000110025), RPS6KL1 (ENSG00000198208)

Protein

Protein identifiers

Ribosomal protein S6 kinase delta-1 — Q96S38 (reviewed: Q96S38)

Alternative names: 52 kDa ribosomal protein S6 kinase, Ribosomal S6 kinase-like protein with two PSK domains 118 kDa protein, SPHK1-binding protein

All UniProt accessions (4): A0A087X1U5, Q96S38, F5H7T0, F6RJM5

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in transmitting sphingosine-1 phosphate (SPP)-mediated signaling into the cell. Plays a role in the recruitment of PRDX3 to early endosomes.

Subunit / interactions. Interacts with SPHK1 and phosphatidylinositol 3-phosphate. Interacts (via PX domain) with PRDX3.

Subcellular location. Cytoplasm. Membrane. Early endosome.

Tissue specificity. Highly expressed in testis, skeletal muscle, brain, heart, placenta, kidney and liver and weakly expressed in thymus, small intestine, lung and colon.

Domain organisation. The PX domain is essential for its localization to the early endosomes. The first protein kinase domain appears to be a pseudokinase domain as it does not contain the classical characteristics, such as the ATP-binding motif, ATP-binding site and active site.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q96S38-1	1	yes
Q96S38-2	2

RefSeq proteins (31): NP_001129610, NP_001274147, NP_001274148, NP_001274149, NP_001274150, NP_001336575, NP_001336576, NP_001336577, NP_001336578, NP_001336579, NP_001336580, NP_001336581, NP_001336582, NP_001336583, NP_001336586, NP_001336587, NP_001336588, NP_001336589, NP_001336590, NP_001336591, NP_001336592, NP_001336593, NP_001336594, NP_001336595, NP_001336596, NP_001336597, NP_001336598, NP_001336599, NP_001336600, NP_001336601, NP_036556* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR001683	PX_dom	Domain
IPR007330	MIT_dom	Domain
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR035053	STK_RPK118-like	Domain
IPR036181	MIT_dom_sf	Homologous_superfamily
IPR036871	PX_dom_sf	Homologous_superfamily
IPR042132	PX_S6K-delta-1	Domain
IPR051866	Intracell_Sig-Traffick_Protein	Family

Pfam: PF00069, PF00787, 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 (48 total): modified residue 16, sequence variant 12, compositionally biased region 5, domain 4, sequence conflict 3, region of interest 3, binding site 2, chain 1, active site 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96S38-F1	56.74	0.16

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): 929 (proton acceptor)

Ligand- & substrate-binding residues (2): 801–809; 820

Post-translational modifications (16): 282, 423, 427, 449, 455, 494, 528, 583, 605, 608, 640, 661, 664, 667, 794, 872

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 126 (showing top): GROSS_HIF1A_TARGETS_DN, GROSS_HYPOXIA_VIA_ELK3_AND_HIF1A_UP, AAAGGGA_MIR204_MIR211, CAIRO_HEPATOBLASTOMA_UP, GCM_NF2, BOYAULT_LIVER_CANCER_SUBCLASS_G12_UP, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, PODAR_RESPONSE_TO_ADAPHOSTIN_UP, MODULE_47, GRYDER_PAX3FOXO1_TOP_ENHANCERS, MASSARWEH_TAMOXIFEN_RESISTANCE_UP, SCGGAAGY_ELK1_02, KRIGE_RESPONSE_TO_TOSEDOSTAT_24HR_UP, GOMF_PROTEIN_KINASE_ACTIVITY, GOMF_KINASE_ACTIVITY

GO Biological Process (2): signal transduction (GO:0007165), protein phosphorylation (GO:0006468)

GO Molecular Function (10): protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), phosphatidylinositol binding (GO:0035091), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), lipid binding (GO:0008289), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (6): lysosome (GO:0005764), endosome (GO:0005768), early endosome (GO:0005769), membrane (GO:0016020), cytoplasm (GO:0005737), organelle (GO:0043226)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
protein kinase activity	2
binding	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
phosphorylation	1
protein modification process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion 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
lytic vacuole	1
endomembrane system	1
cytoplasmic vesicle	1
endosome	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1212 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPS6KC1	TATDN3	Q17R31	551
RPS6KC1	BEND7	Q8N7W2	510
RPS6KC1	OTOL1	A6NHN0	490
RPS6KC1	ANGEL2	Q5VTE6	489
RPS6KC1	LYPD6B	Q8NI32	459
RPS6KC1	ST8SIA5	O15466	451
RPS6KC1	KATNAL2	Q8IYT4	435
RPS6KC1	SHLD1	Q8IYI0	429
RPS6KC1	LOXHD1	Q8IVV2	411
RPS6KC1	GPCPD1	Q9NPB8	406
RPS6KC1	AKT1S1	Q96B36	383
RPS6KC1	OPTN	Q96CV9	381
RPS6KC1	CNOT6L	Q96LI5	379
RPS6KC1	SNX21	Q969T3	374
RPS6KC1	PHYH	O14832	372

IntAct

22 interactions, top by confidence:

A	B	Type	Score
DENND6A	RPS6KC1	psi-mi:“MI:0915”(physical association)	0.560
	RPS6KC1	psi-mi:“MI:0915”(physical association)	0.560
VDR	RPS6KC1	psi-mi:“MI:0915”(physical association)	0.560
RPS6KC1	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.400
RPS6KC1	PRDX3	psi-mi:“MI:0915”(physical association)	0.370
Dennd6a	IFT88	psi-mi:“MI:0914”(association)	0.350
IQGAP1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
VPS39	NPAT	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
DENND6A	EML3	psi-mi:“MI:0914”(association)	0.350
CA10	ENTPD5	psi-mi:“MI:0914”(association)	0.350
TGOLN2	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
	ATF6	psi-mi:“MI:2364”(proximity)	0.270
AGGF1	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
BIN1	RPS6KC1	psi-mi:“MI:0915”(physical association)	0.000
RPS6KC1	VDR	psi-mi:“MI:0915”(physical association)	0.000
RPS6KC1	ETS1	psi-mi:“MI:0915”(physical association)	0.000
PBX2	RPS6KC1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (41): DENND6A (Affinity Capture-MS), RPS6KC1 (Affinity Capture-MS), RPS6KC1 (Affinity Capture-MS), RPS6KC1 (Affinity Capture-MS), RPS6KC1 (Affinity Capture-MS), RPS6KC1 (Proximity Label-MS), RPS6KC1 (Two-hybrid), SAAL1 (Two-hybrid), SPHK1 (Affinity Capture-Western), RPS6KC1 (Proximity Label-MS), RPS6KC1 (Proximity Label-MS), RPS6KC1 (Affinity Capture-RNA), RPS6KC1 (Proximity Label-MS), RPS6KC1 (Proximity Label-MS), RPS6KC1 (Proximity Label-MS)

ESM2 similar proteins: A0A2R6W1B1, A0FKI7, A2XC52, A2XTW9, A2Y0Q2, B8AMA8, B8B8I3, F4I9G2, O94972, P07106, P20067, P41135, P85828, Q5EAE9, Q5EAH9, Q5R7V3, Q5T8D3, Q5XEM9, Q5XG73, Q5XI67, Q6EPZ2, Q6GPE9, Q6IE24, Q6PCX9, Q70EL1, Q75IR6, Q76N89, Q7XUW3, Q84TV4, Q86UB2, Q8BJL1, Q8BL06, Q8CBX9, Q8H383, Q8H8C6, Q8K3A6, Q8K4P8, Q8LA16, Q8TB52, Q96S38

Diamond homologs: A1A4L0, B9DFS6, F1Q506, O14243, O60107, O60493, O70492, O70493, O94291, O95219, P0CR60, P0CR61, P47057, Q08826, Q08DD7, Q0IIL5, Q1RMH8, Q28E02, Q28GP7, Q2U4K2, Q4I1H6, Q4P1V3, Q4V7P7, Q4VAA7, Q4WWS3, Q522W5, Q566W7, Q5A748, Q5AD77, Q5R4C2, Q5R5V1, Q5U211, Q5VWJ9, Q6C2S9, Q6C9X0, Q6CUC4, Q6CY25, Q6FPT9, Q6FT03, Q6NRL2

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PIP3	“up-regulates quantity”	RPS6KC1	binding
RPS6KC1	“up-regulates activity”	SPHK1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	2
Uncertain significance	222
Likely benign	100
Benign	27

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
4683139	NM_012424.6(RPS6KC1):c.2303_2304del (p.Tyr768fs)	Pathogenic
4683140	NM_012424.6(RPS6KC1):c.2783G>C (p.Arg928Pro)	Pathogenic
4683141	NM_012424.6(RPS6KC1):c.895del (p.Arg299fs)	Pathogenic
4683142	NM_012424.6(RPS6KC1):c.1551_1563del (p.Asn517fs)	Pathogenic
4683143	NM_012424.6(RPS6KC1):c.2905G>A (p.Ala969Thr)	Pathogenic
242892	NM_012424.6(RPS6KC1):c.2710G>A (p.Gly904Ser)	Likely pathogenic
242893	Single allele	Likely pathogenic

SpliceAI

3948 predictions. Top by Δscore:

Variant	Effect	Δscore
1:213051507:CGGGT:C	donor_loss	1.0000
1:213051508:GG:G	donor_gain	1.0000
1:213051509:GG:G	donor_gain	1.0000
1:213051510:G:GG	donor_gain	1.0000
1:213051511:T:A	donor_loss	1.0000
1:213051512:GAGT:G	donor_loss	1.0000
1:213071000:TTTTA:T	acceptor_loss	1.0000
1:213071001:TTTAG:T	acceptor_loss	1.0000
1:213071002:TTA:T	acceptor_loss	1.0000
1:213071003:TAG:T	acceptor_loss	1.0000
1:213071039:G:GT	donor_gain	1.0000
1:213077695:GATA:G	acceptor_gain	1.0000
1:213077812:GTTTG:G	donor_gain	1.0000
1:213077815:TGGTA:T	donor_loss	1.0000
1:213077817:G:A	donor_loss	1.0000
1:213077817:G:GG	donor_gain	1.0000
1:213077818:TAAG:T	donor_loss	1.0000
1:213093955:G:GT	donor_gain	1.0000
1:213093979:C:G	donor_gain	1.0000
1:213104449:TGTA:T	acceptor_loss	1.0000
1:213104450:GTA:G	acceptor_loss	1.0000
1:213104452:A:AG	acceptor_gain	1.0000
1:213104452:AG:A	acceptor_gain	1.0000
1:213104452:AGGGC:A	acceptor_gain	1.0000
1:213104453:G:GG	acceptor_gain	1.0000
1:213104453:GG:G	acceptor_gain	1.0000
1:213104453:GGGC:G	acceptor_gain	1.0000
1:213104453:GGGCG:G	acceptor_gain	1.0000
1:213104566:CAAG:C	donor_loss	1.0000
1:213104567:AAG:A	donor_loss	1.0000

AlphaMissense

7063 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:213051454:T:A	V17D	0.999
1:213051499:T:A	V32D	0.999
1:213077745:T:C	L64P	0.999
1:213104485:A:C	R98S	0.999
1:213104485:A:T	R98S	0.999
1:213104505:T:C	L105P	0.999
1:213242201:T:A	W909R	0.999
1:213242201:T:C	W909R	0.999
1:213242226:T:C	L917P	0.999
1:213261599:T:A	W985R	0.999
1:213261599:T:C	W985R	0.999
1:213261602:A:C	S986R	0.999
1:213261604:T:A	S986R	0.999
1:213261604:T:G	S986R	0.999
1:213272525:T:C	L1031P	0.999
1:213051492:T:G	Y30D	0.998
1:213077724:T:C	F57S	0.998
1:213077733:T:C	L60P	0.998
1:213104484:G:C	R98T	0.998
1:213104495:G:C	A102P	0.998
1:213104496:C:A	A102D	0.998
1:213104508:T:C	L106P	0.998
1:213104513:T:C	F108L	0.998
1:213104515:C:A	F108L	0.998
1:213104515:C:G	F108L	0.998
1:213242265:T:C	L930S	0.998
1:213242278:C:A	N934K	0.998
1:213242278:C:G	N934K	0.998
1:213242581:T:C	L945P	0.998
1:213242598:T:A	W951R	0.998

dbSNP variants (sampled 300 via entrez): RS1000002120 (1:213156189 T>C), RS1000003391 (1:213069279 T>G), RS1000008665 (1:213709338 A>G), RS1000010306 (1:213112388 A>C), RS1000014085 (1:213054035 C>G), RS1000014529 (1:213777254 C>T), RS1000017718 (1:213458456 G>C), RS1000023454 (1:213379035 G>T), RS1000026616 (1:213449461 G>A), RS1000030186 (1:213661208 G>A), RS1000063510 (1:213543778 T>C,G), RS1000064611 (1:213290455 G>A), RS1000067671 (1:213061934 A>C,T), RS1000069828 (1:213738438 C>A,T), RS1000070560 (1:213406823 CTGAG>C)

Disease associations

OMIM: gene MIM:617517 | disease phenotypes: MIM:621460

GenCC curated gene-disease

Disease	Classification	Inheritance
periventricular leukomalacia	Limited	Autosomal recessive

Mondo (3): prostate cancer (MONDO:0008315), periventricular leukomalacia (MONDO:0015742), neurodevelopmental disorder with spasticity, thin corpus callosum, and decreased brain white matter (MONDO:0980947)

Orphanet (2): Familial prostate cancer (Orphanet:1331), NON RARE IN EUROPE: Periventricular leukomalacia (Orphanet:171676)

HPO phenotypes

45 total (30 of 45 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000486	Strabismus
HP:0000657	Oculomotor apraxia
HP:0000716	Depression
HP:0000718	Aggressive behavior
HP:0000729	Autistic behavior
HP:0000739	Anxiety
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001256	Mild intellectual disability
HP:0001258	Spastic paraplegia
HP:0001263	Global developmental delay
HP:0001268	Mental deterioration
HP:0001288	Gait disturbance
HP:0001320	Cerebellar vermis hypoplasia
HP:0001324	Muscle weakness
HP:0001332	Dystonia
HP:0001336	Myoclonus
HP:0001337	Tremor
HP:0001347	Hyperreflexia
HP:0001634	Mitral valve prolapse
HP:0001790	Nonimmune hydrops fetalis
HP:0001999	Abnormal facial shape
HP:0002079	Hypoplasia of the corpus callosum
HP:0002280	Enlarged cisterna magna
HP:0002342	Moderate intellectual disability
HP:0002376	Developmental regression
HP:0002460	Distal muscle weakness
HP:0002510	Spastic tetraplegia

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST005110_3	Breast cancer in childhood cancer survivors treated with less than 10 gray radiotherapy	7.000000e-08
GCST005111_5	Breast cancer in childhood cancer survivors	3.000000e-07
GCST010002_377	Refractive error	1.000000e-10
GCST012138_2	Interleukin-6 levels in HIV infection	1.000000e-08
GCST90006994_3	Gut microbiota relative abundance (Ruminococcus belonging to family Erysipelotrichaceae)	1.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004810	interleukin-6 measurement
EFO:0007874	gut microbiome measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D007969	Leukomalacia, Periventricular	C10.228.140.300.700; C10.228.140.461.550; C14.907.253.612; C16.614.521.450
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1795193 (SINGLE PROTEIN)

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

34 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, increases methylation, decreases expression, affects cotreatment	4
Benzo(a)pyrene	decreases expression, increases methylation	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	affects expression, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
arsenite	affects binding, decreases reaction	1
cobaltous chloride	increases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
coumarin	decreases phosphorylation	1
ciglitazone	affects binding, increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
K 7174	increases expression	1
ICG 001	decreases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	affects cotreatment, increases expression	1
bisphenol S	increases methylation	1
Bortezomib	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Doxorubicin	decreases expression	1
Gallic Acid	decreases expression, increases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	1
Thiram	increases expression	1

ChEMBL screening assays

22 unique, capped per target: 22 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1837776	Binding	Inhibition of human RPS6KC1 in HL60 cells lysate at 10 uM using post probe-labeling by LC-MS/MS analysis relative to control	Synthesis and structure-activity relationship of 4-quinolone-3-carboxylic acid based inhibitors of glycogen synthase kinase-3β. — Bioorg Med Chem Lett

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TJ71	HAP1 RPS6KC1 (-) 1	Cancer cell line	Male
CVCL_TJ72	HAP1 RPS6KC1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00120588	PHASE4	COMPLETED	Neuroprotection by Magnesium Sulfate Given to Women at Risk of Very Preterm Birth
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer