symptomatic form of Coffin-Lowry syndrome in female carriers

Summary

symptomatic form of Coffin-Lowry syndrome in female carriers (MONDO:0017193) is a disease with 1 cohort gene.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 1
• Phenotypes (HPO): 21

Clinical features

Signs & symptoms

Clinical features (HPO)

21 HPO clinical features (Orphanet curated; top 21 by frequency):

HPO ID	Term	Frequency
HP:0001176	Large hands	Very frequent (80-99%)
HP:0001182	Tapered finger	Very frequent (80-99%)
HP:0000232	Everted lower lip vermilion	Occasional (5-29%)
HP:0000316	Hypertelorism	Occasional (5-29%)
HP:0000445	Wide nose	Occasional (5-29%)
HP:0000494	Downslanted palpebral fissures	Occasional (5-29%)
HP:0000674	Anodontia	Occasional (5-29%)
HP:0000677	Oligodontia	Occasional (5-29%)
HP:0000709	Psychosis	Occasional (5-29%)
HP:0000716	Depression	Occasional (5-29%)
HP:0000767	Pectus excavatum	Occasional (5-29%)
HP:0000768	Pectus carinatum	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001252	Hypotonia	Occasional (5-29%)
HP:0001513	Obesity	Occasional (5-29%)
HP:0002007	Frontal bossing	Occasional (5-29%)
HP:0002650	Scoliosis	Occasional (5-29%)
HP:0002808	Kyphosis	Occasional (5-29%)
HP:0004322	Short stature	Occasional (5-29%)
HP:0007302	Bipolar affective disorder	Occasional (5-29%)
HP:0030680	Abnormal cardiovascular system morphology	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	symptomatic form of Coffin-Lowry syndrome in female carriers
Mondo ID	MONDO:0017193
Orphanet	276630
UMLS	C5680787
MedGen	1814465
GARD	0021057
Is cancer (heuristic)	no

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › disorder of development or morphogenesis › developmental defect during embryogenesis › multiple congenital anomalies/dysmorphic syndrome › multiple congenital anomalies/dysmorphic syndrome-variable intellectual disability syndrome › symptomatic form of Coffin-Lowry syndrome in female carriers

Related subtypes (68): acromegaloid facial appearance syndrome, Hypoglossia-hypodactyly syndrome, Brachymorphism-onychodysplasia-dysphalangism syndrome, campomelic dysplasia, cerebrocostomandibular syndrome, autosomal dominant popliteal pterygium syndrome, Pallister-Hall syndrome, autosomal dominant primary microcephaly, microgastria-limb reduction defect syndrome, Mobius syndrome, oculodentodigital dysplasia, Char syndrome, Prader-Willi syndrome, Silver-Russell syndrome, ulnar-mammary syndrome, short stature-wormian bones-dextrocardia syndrome, ablepharon macrostomia syndrome, Goodman syndrome, anophthalmia/microphthalmia-esophageal atresia syndrome, microphthalmia with limb anomalies, Antley-Bixler syndrome, campomelia, Cumming type, CHARGE syndrome, Toriello-Carey syndrome, Donnai-Barrow syndrome, lethal faciocardiomelic dysplasia, hypertrichotic osteochondrodysplasia Cantu type, hypomandibular faciocranial dysostosis, isotretinoin-like syndrome, split hand-foot malformation 3, oculotrichoanal syndrome, Hennekam-Beemer syndrome, Mietens syndrome, Schinzel-Giedion syndrome, SHORT syndrome, moyamoya angiopathy-short stature-facial dysmorphism-hypergonadotropic hypogonadism syndrome, occipital horn syndrome, hydrocephalus-costovertebral dysplasia-Sprengel anomaly syndrome, Potocki-Shaffer syndrome, Marshall-Smith syndrome, PHACE syndrome, Noonan syndrome-like disorder with loose anagen hair, branchiogenic deafness syndrome, combined immunodeficiency with faciooculoskeletal anomalies, chromosome 1p32-p31 deletion syndrome, Malan overgrowth syndrome, dysmorphism-conductive hearing loss-heart defect syndrome, TELO2-related intellectual disability-neurodevelopmental disorder, short stature-heart defect-craniofacial anomalies syndrome, arachnodactyly-intellectual disability-dysmorphism syndrome, polyvalvular heart disease syndrome, Kallmann syndrome-heart disease syndrome, Meier-Gorlin syndrome, Prader-Willi-like syndrome, contractures-developmental delay-Pierre Robin syndrome, 22q11.2 deletion syndrome, Noonan syndrome, Carpenter syndrome, Bosley-Salih-Alorainy syndrome, Sotos syndrome, Robinow syndrome, King-Denborough syndrome, Weiss-Kruszka syndrome, retinitis pigmentosa-hearing loss-premature aging-short stature-facial dysmorphism syndrome, omphalocele-diaphragmatic hernia-cardiovascular anomalies-radial ray defect syndrome, 4q25 proximal deletion syndrome, restrictive dermopathy 1, mosaic SMO syndrome

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 3 · 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

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RPS6KA3	HGNC:10432	ENSG00000177189	P51812	Ribosomal protein S6 kinase alpha-3	gencc

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…

Protein-family classification

Druggable: 1 · 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	27.7×	0.036

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

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cartilage tissue	1
colonic mucosa	1
mucosa of sigmoid colon	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

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RPS6KA3	2,713

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RPS6KA3	P51812	15

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 50. Enrichment computed across 1 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 1 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	5617.3×	0.002	RPS6KA3
TORC1 signaling	1	802.5×	0.007	RPS6KA3
toll-like receptor signaling pathway	1	601.9×	0.007	RPS6KA3
positive regulation of cell differentiation	1	267.5×	0.012	RPS6KA3
positive regulation of cell growth	1	183.2×	0.014	RPS6KA3
skeletal system development	1	125.8×	0.014	RPS6KA3
response to lipopolysaccharide	1	124.8×	0.014	RPS6KA3
central nervous system development	1	115.4×	0.014	RPS6KA3
chemical synaptic transmission	1	77.3×	0.019	RPS6KA3
negative regulation of apoptotic process	1	34.8×	0.037	RPS6KA3
regulation of DNA-templated transcription	1	31.6×	0.037	RPS6KA3
signal transduction	1	16.1×	0.067	RPS6KA3
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	RPS6KA3

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 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

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

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: 1; 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	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.