intellectual developmental disorder, X-linked 111

Summary

intellectual developmental disorder, X-linked 111 (MONDO:0957203) is a disease caused by SLITRK2 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: SLITRK2 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 21

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual developmental disorder, X-linked 111
Mondo ID	MONDO:0957203
OMIM	301107
DOID	DOID:0060929
UMLS	C5829568
MedGen	1840204
GARD	0026787
Is cancer (heuristic)	no

Data availability: 21 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 › non-syndromic intellectual disability › non-syndromic X-linked intellectual disability › intellectual developmental disorder, X-linked 111

Related subtypes (51): intellectual disability, X-linked 23, intellectual disability, X-linked 20, intellectual disability, X-linked 14, intellectual disability, X-linked 50, intellectual disability, X-linked 21, intellectual disability, X-linked 58, intellectual disability, X-linked 72, intellectual disability, X-linked 53, intellectual disability, X-linked 73, intellectual disability, X-linked 42, intellectual disability, X-linked 63, intellectual disability, X-linked, with or without seizures, ARX-related, intellectual disability, X-linked 2, intellectual disability, X-linked 81, intellectual disability, X-linked 46, intellectual disability, X-linked 77, intellectual disability, X-linked 45, intellectual disability, X-linked 84, intellectual disability, X-linked 82, intellectual disability, X-linked 30, intellectual disability, X-linked 91, intellectual disability, X-linked 93, chromosome Xp11.22 duplication syndrome, intellectual disability, X-linked 95, intellectual disability, X-linked 96, intellectual disability, X-linked 97, intellectual disability, X-linked 19, intellectual disability, X-linked 89, intellectual disability, X-linked 41, intellectual disability, X-linked 90, intellectual disability, X-linked 92, intellectual disability, X-linked 88, intellectual disability, X-linked 99, intellectual disability, X-linked 100, intellectual disability, X-linked 101, intellectual disability, X-linked 102, intellectual disability, X-linked 61, intellectual disability, X-linked 103, intellectual disability, X-linked 104, intellectual disability, X-linked 105, intellectual disability, X-linked 1, methylmalonic acidemia with homocystinuria, type cblX, FRAXE intellectual disability, intellectual disability, X-linked 9, intellectual developmental disorder, X-linked 108, intellectual disability, X-linked 106, intellectual disability, X-linked 107, intellectual developmental disorder, X-linked 110, intellectual developmental disorder, X-linked 112, intellectual developmental disorder, X-linked 113, intellectual developmental disorder, X-linked 114

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

21 retrieved; paginated sample, class counts are floors:

13 uncertain significance, 3 pathogenic/likely pathogenic, 3 conflicting classifications of pathogenicity, 1 likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1334881	NM_032539.5(SLITRK2):c.1381G>T (p.Glu461Ter)	SLITRK2	Pathogenic/Likely pathogenic	no assertion criteria provided
1334882	NM_032539.5(SLITRK2):c.1121C>G (p.Pro374Arg)	SLITRK2	Pathogenic/Likely pathogenic	no assertion criteria provided
1334905	NM_032539.5(SLITRK2):c.1276C>T (p.Arg426Cys)	SLITRK2	Pathogenic/Likely pathogenic	no assertion criteria provided
1334907	NM_032539.5(SLITRK2):c.934A>G (p.Thr312Ala)	SLITRK2	Likely pathogenic	criteria provided, single submitter
1334908	NM_032539.5(SLITRK2):c.1531G>A (p.Val511Met)	SLITRK2	Conflicting classifications of pathogenicity	no assertion criteria provided
1334909	NM_032539.5(SLITRK2):c.628G>A (p.Glu210Lys)	SLITRK2	Conflicting classifications of pathogenicity	no assertion criteria provided
258948	NM_003126.4(SPTA1):c.5572C>G (p.Leu1858Val)	SPTA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2602647	NM_032539.5(SLITRK2):c.238A>G (p.Asn80Asp)	SLITRK2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2664963	NM_032539.5(SLITRK2):c.2485G>T (p.Glu829Ter)	SLITRK2	Uncertain significance	criteria provided, single submitter
3236625	NM_032539.5(SLITRK2):c.630G>T (p.Glu210Asp)	SLITRK2	Uncertain significance	criteria provided, single submitter
3336952	NM_032539.5(SLITRK2):c.1937G>A (p.Arg646His)	SLITRK2	Uncertain significance	criteria provided, multiple submitters, no conflicts
3775423	NM_032539.5(SLITRK2):c.2330G>T (p.Cys777Phe)	SLITRK2	Uncertain significance	criteria provided, single submitter
3775967	NM_032539.5(SLITRK2):c.1513C>T (p.His505Tyr)	SLITRK2	Uncertain significance	criteria provided, single submitter
4072278	NM_032539.5(SLITRK2):c.844G>T (p.Val282Phe)	SLITRK2	Uncertain significance	criteria provided, single submitter
4076183	NM_032539.5(SLITRK2):c.1111C>T (p.Gln371Ter)	SLITRK2	Uncertain significance	criteria provided, single submitter
4076184	NM_032539.5(SLITRK2):c.4C>G (p.Leu2Val)	SLITRK2	Uncertain significance	criteria provided, single submitter
4080126	NM_032539.5(SLITRK2):c.1782C>G (p.His594Gln)	SLITRK2	Uncertain significance	criteria provided, single submitter
4291777	NM_032539.5(SLITRK2):c.1495C>A (p.Leu499Met)	SLITRK2	Uncertain significance	criteria provided, single submitter
4291791	NM_032539.5(SLITRK2):c.2337A>T (p.Leu779Phe)	SLITRK2	Uncertain significance	criteria provided, single submitter
4532160	NM_032539.5(SLITRK2):c.1951_1952dup (p.Ser652fs)	SLITRK2	Uncertain significance	criteria provided, single submitter
3899944	NM_032539.5(SLITRK2):c.1972AAC[1] (p.Asn659del)	SLITRK2	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 2 · 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
SLITRK2	Strong	X-linked	intellectual developmental disorder, X-linked 111	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SPTA1	Orphanet:288	Hereditary elliptocytosis
SPTA1	Orphanet:822	Hereditary spherocytosis

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
SLITRK2	HGNC:13449	ENSG00000185985	Q9H156	SLIT and NTRK-like protein 2	gencc,clinvar
SPTA1	HGNC:11272	ENSG00000163554	P02549	Spectrin alpha chain, erythrocytic 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLITRK2	SLIT and NTRK-like protein 2	It is involved in synaptogenesis and promotes excitatory synapse differentiation.
SPTA1	Spectrin alpha chain, erythrocytic 1	Spectrin is the major constituent of the cytoskeletal network underlying the erythrocyte plasma membrane.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 1 · 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	8.6×	0.225
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLITRK2	Other/Unknown	no		LRRNT, Cys-rich_flank_reg_C, Leu-rich_rpt
SPTA1	Scaffold/PPI	no		SH3_domain, Spectrin_repeat, EF_hand_dom

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
caudate nucleus	1
medial globus pallidus	1
ventricular zone	1
bone marrow	1
bone marrow cell	1
trabecular bone tissue	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLITRK2	166	broad	marker	ventricular zone, medial globus pallidus, caudate nucleus
SPTA1	147	tissue_specific	marker	trabecular bone tissue, bone marrow, bone marrow cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SPTA1	1,551
SLITRK2	1,442

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SPTA1	P02549	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SLITRK2	Q9H156	67.16

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 21. 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
Receptor-type tyrosine-protein phosphatases	1	285.5×	0.039	SLITRK2
Interaction between L1 and Ankyrins	1	184.2×	0.039	SPTA1
NCAM signaling for neurite out-growth	1	135.9×	0.039	SPTA1
Protein-protein interactions at synapses	1	132.8×	0.039	SLITRK2
ER to Golgi Anterograde Transport	1	66.4×	0.041	SPTA1
MAPK1/MAPK3 signaling	1	65.6×	0.041	SPTA1
L1CAM interactions	1	60.1×	0.041	SPTA1
COPI-mediated anterograde transport	1	54.9×	0.041	SPTA1
MAPK family signaling cascades	1	51.4×	0.041	SPTA1
Transport to the Golgi and subsequent modification	1	51.4×	0.041	SPTA1
RAF/MAP kinase cascade	1	30.5×	0.058	SPTA1
Asparagine N-linked glycosylation	1	30.1×	0.058	SPTA1
Axon guidance	1	22.6×	0.064	SPTA1
Neuronal System	1	22.1×	0.064	SLITRK2
Nervous system development	1	21.5×	0.064	SPTA1
Membrane Trafficking	1	18.5×	0.070	SPTA1
Vesicle-mediated transport	1	17.4×	0.070	SPTA1
Post-translational protein modification	1	9.6×	0.118	SPTA1
Developmental Biology	1	7.2×	0.148	SPTA1
Metabolism of proteins	1	6.2×	0.163	SPTA1
Signal Transduction	1	5.1×	0.187	SPTA1

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
porphyrin-containing compound biosynthetic process	1	2106.5×	0.006	SPTA1
lymphocyte homeostasis	1	936.2×	0.006	SPTA1
actin filament capping	1	766.0×	0.006	SPTA1
plasma membrane organization	1	443.5×	0.007	SPTA1
regulation of synapse organization	1	324.1×	0.007	SLITRK2
synaptic membrane adhesion	1	290.6×	0.007	SLITRK2
regulation of presynapse assembly	1	271.8×	0.007	SLITRK2
hemopoiesis	1	133.8×	0.011	SPTA1
positive regulation of T cell proliferation	1	129.6×	0.011	SPTA1
positive regulation of synapse assembly	1	122.1×	0.011	SLITRK2
axonogenesis	1	80.2×	0.016	SLITRK2
regulation of cell shape	1	61.5×	0.018	SPTA1
actin filament organization	1	59.3×	0.018	SPTA1
actin cytoskeleton organization	1	39.6×	0.025	SPTA1

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 2 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SLITRK2	0	0
SPTA1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
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	SLITRK2, SPTA1

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)
SLITRK2	0	—
SPTA1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.