X-linked intellectual disability, Stocco dos Santos type

Summary

X-linked intellectual disability, Stocco dos Santos type (MONDO:0010325) is a disease with 3 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 3
• ClinVar variants: 43
• Phenotypes (HPO): 17

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		1	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

17 HPO clinical features (Orphanet curated; top 17 by frequency):

HPO ID	Term	Frequency
HP:0001007	Hirsutism	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001518	Small for gestational age	Frequent (30-79%)
HP:0001762	Talipes equinovarus	Frequent (30-79%)
HP:0002205	Recurrent respiratory infections	Frequent (30-79%)
HP:0002808	Kyphosis	Frequent (30-79%)
HP:0004322	Short stature	Frequent (30-79%)
HP:0005280	Depressed nasal bridge	Frequent (30-79%)
HP:0008780	Congenital bilateral hip dislocation	Frequent (30-79%)
HP:0010864	Intellectual disability, severe	Frequent (30-79%)
HP:0000286	Epicanthus	Frequent (30-79%)
HP:0000486	Strabismus	Frequent (30-79%)
HP:0000750	Delayed speech and language development	Frequent (30-79%)
HP:0000752	Hyperactivity	Frequent (30-79%)
HP:0000518	Cataract	Occasional (5-29%)
HP:0001344	Absent speech	Occasional (5-29%)
HP:0003144	Increased serum serotonin	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	X-linked intellectual disability, Stocco dos Santos type
Mondo ID	MONDO:0010325
MeSH	C537495
OMIM	300434
Orphanet	85288
DOID	DOID:0112126
SNOMED CT	718910006
UMLS	C1845530
MedGen	335202
GARD	0001133
Is cancer (heuristic)	no

Also known as: intellectual developmental disorder, X-linked syndromic, Stocco dos Santos type · intellectual disability, Stocco dos Santos type · mental retardation, Stocco dos Santos type · mental retardation, X-linked, Stocco Dos Santos type · SDSX · Stocco dos Santos syndrome · Stocco DOS Santos X-linked mental retardation syndrome

Data availability: 43 ClinVar variants · 2 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 › X-linked intellectual disability, Stocco dos Santos type

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-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, 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

43 retrieved; paginated sample, class counts are floors:

33 uncertain significance, 4 benign, 2 benign/likely benign, 2 conflicting classifications of pathogenicity, 1 likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1321285	NM_020717.5(SHROOM4):c.4212+1G>A	SHROOM4	Likely pathogenic	criteria provided, single submitter
417739	NM_020717.5(SHROOM4):c.436C>T (p.Arg146Trp)	SHROOM4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
425499	NM_020717.5(SHROOM4):c.3104A>C (p.Glu1035Ala)	SHROOM4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1676599	Single allele	CCNB3	Uncertain significance	no assertion criteria provided
1676600	Single allele	MIR502	Uncertain significance	no assertion criteria provided
1029769	NM_020717.5(SHROOM4):c.1157A>G (p.Glu386Gly)	SHROOM4	Uncertain significance	criteria provided, single submitter
1029770	NM_020717.5(SHROOM4):c.1589C>T (p.Ser530Phe)	SHROOM4	Uncertain significance	criteria provided, single submitter
1029771	NM_020717.5(SHROOM4):c.1859T>C (p.Val620Ala)	SHROOM4	Uncertain significance	criteria provided, multiple submitters, no conflicts
1029772	NM_020717.5(SHROOM4):c.2519C>T (p.Thr840Ile)	SHROOM4	Uncertain significance	criteria provided, single submitter
1029773	NM_020717.5(SHROOM4):c.4322G>A (p.Arg1441His)	SHROOM4	Uncertain significance	criteria provided, single submitter
1029774	NM_020717.5(SHROOM4):c.724C>T (p.Arg242Cys)	SHROOM4	Uncertain significance	criteria provided, multiple submitters, no conflicts
1029775	NM_020717.5(SHROOM4):c.775C>A (p.Gln259Lys)	SHROOM4	Uncertain significance	criteria provided, multiple submitters, no conflicts
1033952	NM_020717.5(SHROOM4):c.3541G>C (p.Glu1181Gln)	SHROOM4	Uncertain significance	criteria provided, single submitter
10795	NM_020717.5(SHROOM4):c.3266C>T (p.Ser1089Leu)	SHROOM4	Uncertain significance	no assertion criteria provided
1330243	NM_020717.5(SHROOM4):c.1460T>G (p.Leu487Trp)	SHROOM4	Uncertain significance	criteria provided, single submitter
1342346	NM_020717.5(SHROOM4):c.1214C>A (p.Pro405His)	SHROOM4	Uncertain significance	criteria provided, multiple submitters, no conflicts
1342499	NM_020717.5(SHROOM4):c.1448G>C (p.Arg483Thr)	SHROOM4	Uncertain significance	criteria provided, single submitter
1676597	NM_020717.5(SHROOM4):c.940G>A (p.Glu314Lys)	SHROOM4	Uncertain significance	no assertion criteria provided
1676598	NM_020717.5(SHROOM4):c.3942+1G>A	SHROOM4	Uncertain significance	no assertion criteria provided
1699113	NM_020717.5(SHROOM4):c.2440A>C (p.Met814Leu)	SHROOM4	Uncertain significance	criteria provided, single submitter
1701742	NM_020717.5(SHROOM4):c.679C>T (p.Pro227Ser)	SHROOM4	Uncertain significance	criteria provided, single submitter
1706457	NM_020717.5(SHROOM4):c.3919G>A (p.Asp1307Asn)	SHROOM4	Uncertain significance	criteria provided, multiple submitters, no conflicts
1803118	NM_020717.5(SHROOM4):c.384G>T (p.Trp128Cys)	SHROOM4	Uncertain significance	criteria provided, multiple submitters, no conflicts
2387905	NM_020717.5(SHROOM4):c.1693C>T (p.Arg565Trp)	SHROOM4	Uncertain significance	criteria provided, multiple submitters, no conflicts
2441698	NM_020717.5(SHROOM4):c.326G>T (p.Gly109Val)	SHROOM4	Uncertain significance	criteria provided, single submitter
2441846	NM_020717.5(SHROOM4):c.3166C>T (p.Arg1056Cys)	SHROOM4	Uncertain significance	criteria provided, single submitter
3242058	NM_020717.5(SHROOM4):c.4388T>C (p.Ile1463Thr)	SHROOM4	Uncertain significance	criteria provided, single submitter
3376194	NM_020717.5(SHROOM4):c.1298G>A (p.Gly433Glu)	SHROOM4	Uncertain significance	criteria provided, single submitter
493523	NM_020717.5(SHROOM4):c.2773C>T (p.Arg925Trp)	SHROOM4	Uncertain significance	criteria provided, multiple submitters, no conflicts
587460	NM_020717.5(SHROOM4):c.3955G>A (p.Glu1319Lys)	SHROOM4	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · 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
SHROOM4	Supportive	X-linked	X-linked intellectual disability, Stocco dos Santos type	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SHROOM4	Orphanet:85288	X-linked intellectual disability, Stocco Dos Santos type

Cohort genes → proteins

3 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SHROOM4	HGNC:29215	ENSG00000158352	Q9ULL8	Protein Shroom4	gencc,clinvar
CCNB3	HGNC:18709	ENSG00000147082	Q8WWL7	G2/mitotic-specific cyclin-B3	clinvar
MIR502	HGNC:32136	ENSG00000272080		microRNA 502	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SHROOM4	Protein Shroom4	Probable regulator of cytoskeletal architecture that plays an important role in development.
CCNB3	G2/mitotic-specific cyclin-B3	Cyclins are positive regulatory subunits of the cyclin-dependent kinases (CDKs), and thereby play an essential role in the control of the cell cycle, notably via their destruction during cell division.

Protein-family classification

Druggable: 0 · Difficult: 1 · 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
Scaffold/PPI	1	5.8×	0.327
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SHROOM4	Scaffold/PPI	no		PDZ, ASD2_dom, Shroom_fam
CCNB3	Other/Unknown	no		Cyclin_C-dom, Cyclin_N, Cyclin-like_dom
MIR502	Other/Unknown	no

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)	1
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
buccal mucosa cell	1
left ventricle myocardium	1
tendon of biceps brachii	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
secondary oocyte	1
blood	1
colon	1
intestine	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SHROOM4	190	broad	marker	buccal mucosa cell, tendon of biceps brachii, left ventricle myocardium
CCNB3	156	tissue_specific	yes	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, secondary oocyte
MIR502	11		yes	blood, colon, intestine

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CCNB3	2,576
SHROOM4	1,736
MIR502	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SHROOM4	Q9ULL8	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CCNB3	Q8WWL7	42.25

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 3 evidence-associated genes (0 with Reactome annotation).

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 postsynaptic membrane neurotransmitter receptor levels	1	247.8×	0.020	SHROOM4
cognition	1	142.8×	0.020	SHROOM4
meiotic cell cycle	1	122.1×	0.020	CCNB3
G1/S transition of mitotic cell cycle	1	100.3×	0.020	CCNB3
actin filament organization	1	59.3×	0.027	SHROOM4
brain development	1	39.8×	0.029	SHROOM4
actin cytoskeleton organization	1	39.6×	0.029	SHROOM4
cell division	1	23.1×	0.043	CCNB3

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) 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
CCNB3	PALBOCICLIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CCNB3	17	4
SHROOM4	0	0
MIR502	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PALBOCICLIB	4	CCNB3
DINACICLIB	3	CCNB3
ALVOCIDIB	3	CCNB3
QUERCETIN	3	CCNB3
SILMITASERTIB	2	CCNB3
INDIRUBIN	2	CCNB3
SELICICLIB	2	CCNB3
LUTEOLIN	2	CCNB3
ASNUCICLIB	2	CCNB3
FISETIN	2	CCNB3
RIVICICLIB	2	CCNB3
AT-7519	2	CCNB3
KAEMPFEROL	1	CCNB3
SU-9516	1	CCNB3
HARMINE	1	CCNB3
BMS-387032	1	CCNB3
LADUVIGLUSIB	1	CCNB3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
CCNB3	148	Binding:147, Functional:1

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
CCNB3	148

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

17 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)
PALBOCICLIB	4	CCNB3
DINACICLIB	3	CCNB3
ALVOCIDIB	3	CCNB3
QUERCETIN	3	CCNB3
SILMITASERTIB	2	CCNB3
INDIRUBIN	2	CCNB3
SELICICLIB	2	CCNB3
LUTEOLIN	2	CCNB3
ASNUCICLIB	2	CCNB3
FISETIN	2	CCNB3
RIVICICLIB	2	CCNB3
AT-7519	2	CCNB3
KAEMPFEROL	1	CCNB3
SU-9516	1	CCNB3
HARMINE	1	CCNB3
BMS-387032	1	CCNB3
LADUVIGLUSIB	1	CCNB3

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CCNB3
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	2	SHROOM4, MIR502

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SHROOM4	0	—
MIR502	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.