Coffin-Lowry syndrome

Summary

Coffin-Lowry syndrome (MONDO:0010561) is a disease caused by RPS6KA3 (GenCC Definitive), with 2 cohort genes and 1 clinical trial.

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Causal gene: RPS6KA3 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 323
• Phenotypes (HPO): 81
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	1.5	Europe	Validated
Point prevalence	1-9 / 100 000	1.5	Worldwide	Not yet validated

Signs & symptoms

Clinical features (HPO)

81 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0001382	Joint hypermobility	Very frequent (80-99%)
HP:0000179	Thick lower lip vermilion	Very frequent (80-99%)
HP:0000194	Open mouth	Very frequent (80-99%)
HP:0000232	Everted lower lip vermilion	Very frequent (80-99%)
HP:0000280	Coarse facial features	Very frequent (80-99%)
HP:0000286	Epicanthus	Very frequent (80-99%)
HP:0000316	Hypertelorism	Very frequent (80-99%)
HP:0000463	Anteverted nares	Very frequent (80-99%)
HP:0000494	Downslanted palpebral fissures	Very frequent (80-99%)
HP:0000668	Hypodontia	Very frequent (80-99%)
HP:0000687	Widely spaced teeth	Very frequent (80-99%)
HP:0000767	Pectus excavatum	Very frequent (80-99%)
HP:0000768	Pectus carinatum	Very frequent (80-99%)
HP:0000940	Abnormal diaphysis morphology	Very frequent (80-99%)
HP:0001176	Large hands	Very frequent (80-99%)
HP:0001182	Tapered finger	Very frequent (80-99%)
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0001252	Hypotonia	Very frequent (80-99%)
HP:0001500	Broad finger	Very frequent (80-99%)
HP:0002007	Frontal bossing	Very frequent (80-99%)
HP:0002167	Abnormality of speech or vocalization	Very frequent (80-99%)
HP:0002650	Scoliosis	Very frequent (80-99%)
HP:0002750	Delayed skeletal maturation	Very frequent (80-99%)
HP:0002808	Kyphosis	Very frequent (80-99%)
HP:0003312	Abnormal form of the vertebral bodies	Very frequent (80-99%)
HP:0004322	Short stature	Very frequent (80-99%)
HP:0004493	Craniofacial hyperostosis	Very frequent (80-99%)
HP:0005280	Depressed nasal bridge	Very frequent (80-99%)
HP:0006482	Abnormal dental morphology	Very frequent (80-99%)
HP:0009928	Thick nasal alae	Very frequent (80-99%)
HP:0011344	Severe global developmental delay	Very frequent (80-99%)
HP:0000154	Wide mouth	Frequent (30-79%)
HP:0000189	Narrow palate	Frequent (30-79%)
HP:0000218	High palate	Frequent (30-79%)
HP:0000252	Microcephaly	Frequent (30-79%)
HP:0000327	Hypoplasia of the maxilla	Frequent (30-79%)
HP:0000411	Protruding ear	Frequent (30-79%)
HP:0000445	Wide nose	Frequent (30-79%)
HP:0001276	Hypertonia	Frequent (30-79%)
HP:0001288	Gait disturbance	Frequent (30-79%)
HP:0001582	Redundant skin	Frequent (30-79%)
HP:0001763	Pes planus	Frequent (30-79%)
HP:0001804	Hypoplastic fingernail	Frequent (30-79%)
HP:0001812	Hyperconvex fingernails	Frequent (30-79%)
HP:0002119	Ventriculomegaly	Frequent (30-79%)
HP:0002191	Progressive spasticity	Frequent (30-79%)
HP:0002868	Narrow iliac wings	Frequent (30-79%)
HP:0006480	Premature loss of teeth	Frequent (30-79%)
HP:0006692	Short chordae tendineae of the tricuspid valve	Frequent (30-79%)
HP:0008872	Feeding difficulties in infancy	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Coffin-Lowry syndrome
Mondo ID	MONDO:0010561
MeSH	C536435, D038921
OMIM	303600
Orphanet	192
DOID	DOID:3783
ICD-11	380089065
NCIT	C84643
SNOMED CT	15182000
UMLS	C0265252
MedGen	75556
GARD	0006123
NORD	983
Is cancer (heuristic)	no

Also known as: CLS · Coffin Lowry Syndrome · Coffin syndrome · Coffin syndrome 1 · Coffin-Lowry syndrome · Coffin-Lowry syndrome, X-linked dominant · dwarfism, lean spastic type · intellectual disability with osteocartilaginous abnormalities · lean spastic dwarfism · mental retardation with osteocartilaginous abnormalities

Data availability: 323 ClinVar variants · 6 GenCC gene-disease records · 5 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › neurodevelopmental disorder › intellectual disability › syndromic intellectual disability › X-linked syndromic intellectual disability › Coffin-Lowry syndrome

Related subtypes (80): X-linked intellectual disability-psychosis-macroorchidism syndrome, X-linked intellectual disability-plagiocephaly syndrome, intellectual disability, X-linked 49, MEHMO syndrome, syndromic X-linked intellectual disability 7, syndromic X-linked intellectual disability Shashi type, syndromic X-linked intellectual disability Lubs type, syndromic X-linked intellectual disability Abidi type, syndromic X-linked intellectual disability Siderius type, X-linked intellectual disability, Cabezas type, X-linked intellectual disability, Stocco dos Santos type, X-linked intellectual disability-cubitus valgus-dysmorphism syndrome, corpus callosum agenesis-intellectual disability-coloboma-micrognathia syndrome, X-linked intellectual disability-cerebellar hypoplasia syndrome, Allan-Herndon-Dudley syndrome, syndromic X-linked intellectual disability Claes-Jensen type, X-linked intellectual disability-retinitis pigmentosa syndrome, syndromic X-linked intellectual disability 14, syndromic X-linked intellectual disability 94, intellectual disability, X-linked syndromic, Turner type, syndromic X-linked intellectual disability Shrimpton type, X-linked intellectual disability-craniofacioskeletal syndrome, syndromic X-linked intellectual disability Raymond type, syndromic X-linked intellectual disability 17, syndromic X-linked intellectual disability Nascimento type, syndromic X-linked intellectual disability Chudley-Schwartz type, X-linked intellectual disability-cardiomegaly-congestive heart failure syndrome, X-linked intellectual disability, Cantagrel type, X-linked intellectual disability-short stature-overweight syndrome, intellectual disability, X-linked, syndromic 33, syndromic X-linked intellectual disability 34, intellectual disability, X-linked 99, syndromic, female-restricted, intellectual disability, X-linked, syndromic, Bain type, Borjeson-Forssman-Lehmann syndrome, syndromic X-linked intellectual disability 5, X-linked intellectual disability-seizures-psoriasis syndrome, Renpenning syndrome, Partington syndrome, syndromic X-linked intellectual disability 12, severe X-linked intellectual disability, Gustavson type, syndromic X-linked intellectual disability Snyder type, Wilson-Turner syndrome, Prieto syndrome, skeletal dysplasia-intellectual disability syndrome, X-linked intellectual disability-spastic quadriparesis syndrome, early-onset parkinsonism-intellectual disability syndrome, X-linked intellectual disability, Schimke type, X-linked intellectual disability, Cilliers type, X-linked intellectual disability, van Esch type, X-linked intellectual disability-epilepsy syndrome, ATR-X-related syndrome, X-linked intellectual disability-hypogonadism-ichthyosis-obesity-short stature syndrome, X-linked intellectual disability, Schutz type, X-linked intellectual disability-hypotonia-movement disorder syndrome, X-linked intellectual disability with isolated growth hormone deficiency, X-linked intellectual disability-hypogammaglobulinemia-progressive neurological deterioration syndrome, X-linked intellectual disability-precocious puberty-obesity syndrome, X-linked intellectual disability-epilepsy-progressive joint contractures-dysmorphism syndrome, X-linked intellectual disability-macrocephaly-macroorchidism syndrome, X-linked intellectual disability, Pai type, X-linked intellectual disability, Seemanova type, X-linked intellectual disability, Stevenson type, X-linked intellectual disability, Stoll type, X-linked intellectual disability-acromegaly-hyperactivity syndrome, X-linked intellectual disability-corpus callosum agenesis-spastic quadriparesis syndrome, fried syndrome, X-linked intellectual disability-ataxia-apraxia syndrome, intellectual developmental disorder, X-linked, syndromic, Pilorge type, Paganini-Miozzo syndrome, intellectual developmental disorder, X-linked, syndromic, Hackmann-Di Donato type, intellectual disability, X-linked, syndromic, 35, intellectual disability, X-linked, syndromic, Houge type, MED12-related intellectual disability syndrome, NAA10-related syndrome, ATP6AP2-related disorder, X-linked intellectual disability with hypopituitarism, SOX3-related X-linked pituitary hormone deficiency with or without intellectual developmental disorder, intellectual developmental disorder, X-linked, syndromic, with pigmentary mosaicism and coarse facies, intellectual developmental disorder, X-linked, syndromic 37, CASK-related intellectual disability

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

323 retrieved; paginated sample, class counts are floors:

86 likely benign, 69 uncertain significance, 66 pathogenic, 39 benign, 27 likely pathogenic, 15 benign/likely benign, 15 conflicting classifications of pathogenicity, 6 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3243867	NC_000023.10:g.(?17393881)(20284750_?)del	ADGRG2	Pathogenic	criteria provided, single submitter
1065479	NM_004586.3(RPS6KA3):c.432T>G (p.Tyr144Ter)	RPS6KA3	Pathogenic	criteria provided, single submitter
1073446	NC_000023.10:g.(?20204394)(20206108_?)del	RPS6KA3	Pathogenic	criteria provided, single submitter
1074355	NM_004586.3(RPS6KA3):c.251del (p.Phe83_Leu84insTer)	RPS6KA3	Pathogenic	criteria provided, single submitter
1164016	NM_004586.3(RPS6KA3):c.1152del (p.Phe385fs)	RPS6KA3	Pathogenic	no assertion criteria provided
11650	RPS6KA3, 187-BP DEL, NT406	RPS6KA3	Pathogenic	no assertion criteria provided
11651	NM_004586.3(RPS6KA3):c.224G>T (p.Gly75Val)	RPS6KA3	Pathogenic	no assertion criteria provided
11652	NM_004586.3(RPS6KA3):c.679T>G (p.Ser227Ala)	RPS6KA3	Pathogenic	no assertion criteria provided
11653	NM_004586.3(RPS6KA3):c.244G>T (p.Val82Phe)	RPS6KA3	Pathogenic	no assertion criteria provided
11654	NM_004586.3(RPS6KA3):c.326-1G>C	RPS6KA3	Pathogenic	no assertion criteria provided
11656	NM_004586.3(RPS6KA3):c.451_452del (p.Arg151fs)	RPS6KA3	Pathogenic	criteria provided, single submitter
11657	NM_004586.3(RPS6KA3):c.2065C>T (p.Gln689Ter)	RPS6KA3	Pathogenic	no assertion criteria provided
11658	NM_004586.3(RPS6KA3):c.2186G>A (p.Arg729Gln)	RPS6KA3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
11660	NM_004586.3(RPS6KA3):c.566T>A (p.Ile189Lys)	RPS6KA3	Pathogenic	no assertion criteria provided
11661	NM_004586.3(RPS6KA3):c.486+3A>G	RPS6KA3	Pathogenic	no assertion criteria provided
11663	NM_004586.3(RPS6KA3):c.2144del (p.Ser715fs)	RPS6KA3	Pathogenic	no assertion criteria provided
11664	NM_004586.3(RPS6KA3):c.1000-2A>G	RPS6KA3	Pathogenic	no assertion criteria provided
11665	NG_007488.1:g.67535_67536ins[N[2800];67522_67535]	RPS6KA3	Pathogenic	no assertion criteria provided
11666	NM_004586.3(RPS6KA3):c.803T>C (p.Phe268Ser)	RPS6KA3	Pathogenic	no assertion criteria provided
11667	NM_004586.3(RPS6KA3):c.1428_1430del (p.Ile477del)	RPS6KA3	Pathogenic	no assertion criteria provided
11668	NM_004586.3(RPS6KA3):c.1444_1959dup (p.Val482_Lys653dup)	RPS6KA3	Pathogenic	no assertion criteria provided
1332821	NM_004586.3(RPS6KA3):c.632-2A>C	RPS6KA3	Pathogenic	criteria provided, single submitter
1451836	NM_004586.3(RPS6KA3):c.740dup (p.Ser248fs)	RPS6KA3	Pathogenic	criteria provided, single submitter
1455251	NM_004586.3(RPS6KA3):c.770_773del (p.Leu257fs)	RPS6KA3	Pathogenic	criteria provided, single submitter
1476999	NM_004586.3(RPS6KA3):c.2142_2145dup (p.Pro716fs)	RPS6KA3	Pathogenic	criteria provided, single submitter
1695288	NM_004586.3(RPS6KA3):c.262dup (p.Ile88fs)	RPS6KA3	Pathogenic	criteria provided, multiple submitters, no conflicts
1805036	NM_004586.3(RPS6KA3):c.889_890del (p.Leu298fs)	RPS6KA3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
190301	NC_000023.10:g.(20185970_20187287)_(20191368_20193188)del	RPS6KA3	Pathogenic	no assertion criteria provided
2050023	NM_004586.3(RPS6KA3):c.1814G>A (p.Gly605Asp)	RPS6KA3	Pathogenic	criteria provided, single submitter
2106659	NM_004586.3(RPS6KA3):c.709C>T (p.Pro237Ser)	RPS6KA3	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
RPS6KA3	Definitive	X-linked	Coffin-Lowry syndrome	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RPS6KA3	Orphanet:192	Coffin-Lowry syndrome
RPS6KA3	Orphanet:276630	Symptomatic form of Coffin-Lowry syndrome in female carriers
RPS6KA3	Orphanet:777	X-linked non-syndromic intellectual disability
ADGRG2	Orphanet:48	Congenital bilateral absence of vas deferens

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RPS6KA3	HGNC:10432	ENSG00000177189	P51812	Ribosomal protein S6 kinase alpha-3	gencc,clinvar
ADGRG2	HGNC:4516	ENSG00000173698	Q8IZP9	Adhesion G-protein coupled receptor G2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RPS6KA3	Ribosomal protein S6 kinase alpha-3	Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation thr…
ADGRG2	Adhesion G-protein coupled receptor G2	Adhesion G-protein coupled receptor (aGPCR) for steroid hormones, such as dehydroepiandrosterone (DHEA; also named 3beta-hydroxyandrost-5-en-17-one) and androstenedione.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Kinase	1	13.9×	0.082
GPCR	1	12.0×	0.082

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RPS6KA3	Kinase	yes	2.7.11.1	Prot_kinase_dom, AGC-kinase_C, Ser/Thr_kinase_AS
ADGRG2	GPCR	yes		GPS, GPCR_2_secretin-like, GPCR_2-like_7TM

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cartilage tissue	1
colonic mucosa	1
mucosa of sigmoid colon	1
caput epididymis	1
corpus epididymis	1
parotid gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RPS6KA3	285	ubiquitous	marker	cartilage tissue, mucosa of sigmoid colon, colonic mucosa
ADGRG2	182	broad	marker	corpus epididymis, caput epididymis, parotid gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RPS6KA3	2,713
ADGRG2	723

Structural data

PDB: 1 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RPS6KA3	P51812	15

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ADGRG2	Q8IZP9	62.76

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 50. Enrichment computed across 2 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
CREB phosphorylation	1	1631.4×	0.011	RPS6KA3
RSK activation	1	1427.5×	0.011	RPS6KA3
CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling	1	878.5×	0.011	RPS6KA3
Gastrin-CREB signalling pathway via PKC and MAPK	1	878.5×	0.011	RPS6KA3
ERK/MAPK targets	1	671.8×	0.011	RPS6KA3
MAPK targets/ Nuclear events mediated by MAP kinases	1	543.8×	0.011	RPS6KA3
Nuclear Events (kinase and transcription factor activation)	1	346.1×	0.011	RPS6KA3
MAP kinase activation	1	308.6×	0.011	RPS6KA3
Interleukin-17 signaling	1	253.8×	0.011	RPS6KA3
Recycling pathway of L1	1	223.9×	0.011	RPS6KA3
Toll Like Receptor 10 (TLR10) Cascade	1	215.5×	0.011	RPS6KA3
Toll Like Receptor 5 (TLR5) Cascade	1	215.5×	0.011	RPS6KA3
Post NMDA receptor activation events	1	203.9×	0.011	RPS6KA3
MyD88 cascade initiated on plasma membrane	1	203.9×	0.011	RPS6KA3
Signaling by NTRK1 (TRKA)	1	196.9×	0.011	RPS6KA3
Toll Like Receptor 3 (TLR3) Cascade	1	193.6×	0.011	RPS6KA3
TRIF (TICAM1)-mediated TLR4 signaling	1	190.3×	0.011	RPS6KA3
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation	1	190.3×	0.011	RPS6KA3
MyD88 dependent cascade initiated on endosome	1	190.3×	0.011	RPS6KA3
MyD88-independent TLR4 cascade	1	184.2×	0.011	RPS6KA3
Toll Like Receptor 7/8 (TLR7/8) Cascade	1	184.2×	0.011	RPS6KA3
Activation of NMDA receptors and postsynaptic events	1	184.2×	0.011	RPS6KA3
Signaling by NTRKs	1	181.3×	0.011	RPS6KA3
Toll Like Receptor 9 (TLR9) Cascade	1	175.7×	0.011	RPS6KA3
Toll Like Receptor TLR6:TLR2 Cascade	1	175.7×	0.011	RPS6KA3
Toll Like Receptor 2 (TLR2) Cascade	1	173.0×	0.011	RPS6KA3
Toll Like Receptor TLR1:TLR2 Cascade	1	167.9×	0.011	RPS6KA3
MyD88:MAL(TIRAP) cascade initiated on plasma membrane	1	152.3×	0.012	RPS6KA3
Cellular Senescence	1	137.6×	0.013	RPS6KA3
Toll Like Receptor 4 (TLR4) Cascade	1	131.3×	0.013	RPS6KA3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of translation in response to stress	1	2808.7×	0.007	RPS6KA3
TORC1 signaling	1	401.2×	0.021	RPS6KA3
toll-like receptor signaling pathway	1	300.9×	0.021	RPS6KA3
positive regulation of cell differentiation	1	133.8×	0.030	RPS6KA3
positive regulation of cell growth	1	91.6×	0.030	RPS6KA3
spermatid development	1	72.6×	0.030	ADGRG2
phospholipase C-activating G protein-coupled receptor signaling pathway	1	65.8×	0.030	ADGRG2
skeletal system development	1	62.9×	0.030	RPS6KA3
response to lipopolysaccharide	1	62.4×	0.030	RPS6KA3
central nervous system development	1	57.7×	0.030	RPS6KA3
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1	56.5×	0.030	ADGRG2
chemical synaptic transmission	1	38.6×	0.041	RPS6KA3
cell surface receptor signaling pathway	1	32.0×	0.045	ADGRG2
G protein-coupled receptor signaling pathway	1	18.1×	0.067	ADGRG2
spermatogenesis	1	17.6×	0.067	ADGRG2
negative regulation of apoptotic process	1	17.4×	0.067	RPS6KA3
regulation of DNA-templated transcription	1	15.8×	0.070	RPS6KA3
signal transduction	1	8.0×	0.127	RPS6KA3
positive regulation of transcription by RNA polymerase II	1	7.4×	0.130	RPS6KA3

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 1

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
RPS6KA3	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RPS6KA3	46	4
ADGRG2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FEDRATINIB	4	RPS6KA3
PALBOCICLIB	4	RPS6KA3
ENTRECTINIB	4	RPS6KA3
BOSUTINIB	4	RPS6KA3
GILTERITINIB	4	RPS6KA3
BRIGATINIB	4	RPS6KA3
UPADACITINIB	4	RPS6KA3
NINTEDANIB	4	RPS6KA3
SUNITINIB	4	RPS6KA3
QUIZARTINIB	4	RPS6KA3
MIDOSTAURIN	4	RPS6KA3
ENZASTAURIN	3	RPS6KA3
FASUDIL	3	RPS6KA3
ALVOCIDIB	3	RPS6KA3
ALISERTIB	3	RPS6KA3
DOVITINIB	3	RPS6KA3
LESTAURTINIB	3	RPS6KA3
RUBOXISTAURIN	3	RPS6KA3
PAMAPIMOD	2	RPS6KA3
MOLIBRESIB	2	RPS6KA3
LUTEOLIN	2	RPS6KA3
SU-014813	2	RPS6KA3
ILORASERTIB	2	RPS6KA3
LAUROGUADINE	2	RPS6KA3
FISETIN	2	RPS6KA3
LY-2090314	2	RPS6KA3
CERDULATINIB	2	RPS6KA3
R-406	2	RPS6KA3
AT-9283	2	RPS6KA3
PICTILISIB	2	RPS6KA3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
RPS6KA3	770	Binding:768, Functional:1, ADMET:1
ADGRG2	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
RPS6KA3	2.7.11.1	non-specific serine/threonine protein kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
RPS6KA3	770

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
FEDRATINIB	4	RPS6KA3
PALBOCICLIB	4	RPS6KA3
ENTRECTINIB	4	RPS6KA3
BOSUTINIB	4	RPS6KA3
GILTERITINIB	4	RPS6KA3
BRIGATINIB	4	RPS6KA3
UPADACITINIB	4	RPS6KA3
NINTEDANIB	4	RPS6KA3
SUNITINIB	4	RPS6KA3
QUIZARTINIB	4	RPS6KA3
MIDOSTAURIN	4	RPS6KA3
ENZASTAURIN	3	RPS6KA3
FASUDIL	3	RPS6KA3
ALVOCIDIB	3	RPS6KA3
ALISERTIB	3	RPS6KA3
DOVITINIB	3	RPS6KA3
LESTAURTINIB	3	RPS6KA3
RUBOXISTAURIN	3	RPS6KA3
PAMAPIMOD	2	RPS6KA3
MOLIBRESIB	2	RPS6KA3
LUTEOLIN	2	RPS6KA3
SU-014813	2	RPS6KA3
ILORASERTIB	2	RPS6KA3
LAUROGUADINE	2	RPS6KA3
FISETIN	2	RPS6KA3
LY-2090314	2	RPS6KA3
CERDULATINIB	2	RPS6KA3
R-406	2	RPS6KA3
AT-9283	2	RPS6KA3
PICTILISIB	2	RPS6KA3

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	RPS6KA3
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	ADGRG2
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
ADGRG2	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford