intellectual disability, X-linked, syndromic, 35

Summary

intellectual disability, X-linked, syndromic, 35 (MONDO:0030908) is a disease caused by RPL10 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: RPL10 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 14

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual disability, X-linked, syndromic, 35
Mondo ID	MONDO:0030908
OMIM	300998
DOID	DOID:0080241
UMLS	C4478383
MedGen	1392054
GARD	0025657
Is cancer (heuristic)	no

Also known as: intellectual developmental disorder, X-linked, syndromic, 35, X-linked recessive · intellectual disability, X-linked, syndromic, 35 · mental retardation, X-linked, syndromic, 35 · MRXS35 · syndromic X-linked mental retardation 35

Data availability: 14 ClinVar variants · 4 GenCC gene-disease records.

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 › intellectual disability, X-linked, syndromic, 35

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, Coffin-Lowry 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, 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

14 retrieved; paginated sample, class counts are floors:

8 uncertain significance, 4 pathogenic, 1 benign, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3242417	NM_006013.5(RPL10):c.452C>T (p.Ala151Val)	RPL10	Pathogenic	no assertion criteria provided
430612	NM_006013.5(RPL10):c.232A>G (p.Lys78Glu)	RPL10	Pathogenic	criteria provided, single submitter
430613	NM_006013.5(RPL10):c.481G>A (p.Gly161Ser)	RPL10	Pathogenic	no assertion criteria provided
430614	NM_006013.5(RPL10):c.191C>T (p.Ala64Val)	RPL10	Pathogenic	no assertion criteria provided
818225	NM_006013.5(RPL10):c.565C>T (p.Arg189Trp)	RPL10	Likely pathogenic	criteria provided, single submitter
1028473	NM_006013.5(RPL10):c.191-5C>T	RPL10	Uncertain significance	criteria provided, single submitter
1031592	NM_006013.5(RPL10):c.347G>A (p.Arg116Gln)	RPL10	Uncertain significance	criteria provided, multiple submitters, no conflicts
1679194	NM_006013.5(RPL10):c.218A>C (p.Asn73Thr)	RPL10	Uncertain significance	no assertion criteria provided
1802573	NM_006013.5(RPL10):c.535G>A (p.Asp179Asn)	RPL10	Uncertain significance	criteria provided, single submitter
3024241	NM_006013.5(RPL10):c.214G>A (p.Ala72Thr)	RPL10	Uncertain significance	criteria provided, single submitter
3340698	NM_006013.5(RPL10):c.218A>G (p.Asn73Ser)	RPL10	Uncertain significance	criteria provided, multiple submitters, no conflicts
931462	NM_006013.5(RPL10):c.236G>C (p.Ser79Thr)	RPL10	Uncertain significance	criteria provided, multiple submitters, no conflicts
977077	NM_006013.5(RPL10):c.578A>G (p.Asp193Gly)	RPL10	Uncertain significance	criteria provided, multiple submitters, no conflicts
1327969	NM_006013.5(RPL10):c.-24+3G>A	LOC130068867	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 19 · 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
RPL10	Definitive	X-linked	intellectual disability, X-linked, syndromic, 35	8
RPL15	Definitive	X-linked	intellectual disability, X-linked, syndromic, 35	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RPL10	Orphanet:435938	X-linked microcephaly-growth retardation-prognathism-cryptorchidism syndrome
RPL10	Orphanet:459070	X-linked intellectual disability-cerebellar hypoplasia-spondylo-epiphyseal dysplasia syndrome
RPL15	Orphanet:124	Diamond-Blackfan anemia

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
RPL10	HGNC:10298	ENSG00000147403	P27635	Large ribosomal subunit protein uL16	gencc,clinvar
RPL15	HGNC:10306	ENSG00000174748	P61313	Large ribosomal subunit protein eL15	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RPL10	Large ribosomal subunit protein uL16	Component of the large ribosomal subunit.
RPL15	Large ribosomal subunit protein eL15	Component of the large ribosomal subunit.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.0

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
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RPL10	Other/Unknown	no		Ribosomal_uL16_euk_arch, Ribosomal_uL16_dom, Ribosomal_uL16_CS_euk_arc
RPL15	Other/Unknown	no		Ribosomal_eL15, Ribosomal_uL23/eL15/eS24_sf, Ribosomal_eL15_CS

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
left ovary	2
right ovary	2
endocervix	1
cortical plate	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RPL10	170	ubiquitous	marker	endocervix, right ovary, left ovary
RPL15	303	ubiquitous	marker	left ovary, cortical plate, right ovary

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RPL10	5,485
RPL15	1,011

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RPL15	P61313	192
RPL10	P27635	43

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Peptide chain elongation	2	126.9×	1e-04	RPL10, RPL15
Viral mRNA Translation	2	126.9×	1e-04	RPL10, RPL15
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	2	125.5×	1e-04	RPL10, RPL15
Selenocysteine synthesis	2	120.2×	1e-04	RPL10, RPL15
Eukaryotic Translation Termination	2	120.2×	1e-04	RPL10, RPL15
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	2	117.7×	1e-04	RPL10, RPL15
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	2	117.7×	1e-04	RPL10, RPL15
Formation of a pool of free 40S subunits	2	112.0×	1e-04	RPL10, RPL15
Response of EIF2AK4 (GCN2) to amino acid deficiency	2	110.9×	1e-04	RPL10, RPL15
Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide	2	106.7×	1e-04	RPL10, RPL15
L13a-mediated translational silencing of Ceruloplasmin expression	2	101.1×	1e-04	RPL10, RPL15
SRP-dependent cotranslational protein targeting to membrane	2	100.2×	1e-04	RPL10, RPL15
GTP hydrolysis and joining of the 60S ribosomal subunit	2	100.2×	1e-04	RPL10, RPL15
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	2	97.6×	1e-04	RPL10, RPL15
Regulation of expression of SLITs and ROBOs	2	69.2×	2e-04	RPL10, RPL15
Major pathway of rRNA processing in the nucleolus and cytosol	2	61.7×	3e-04	RPL10, RPL15

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
cytoplasmic translation	2	185.2×	1e-04	RPL10, RPL15
translation	2	102.8×	2e-04	RPL10, RPL15
embryonic brain development	1	401.2×	0.004	RPL10
intracellular signal transduction	1	19.1×	0.065	RPL10
negative regulation of transcription by RNA polymerase II	1	8.9×	0.110	RPL10

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 0

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
RPL10	GENTAMICIN SULFATE
RPL15	GENTAMICIN SULFATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RPL10	1	4
RPL15	1	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
GENTAMICIN SULFATE	4	RPL10, RPL15

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
RPL10	90	Binding:90
RPL15	90	Binding:90

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

1 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)
GENTAMICIN SULFATE	4	RPL10, RPL15

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	RPL10, RPL15
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.