intellectual developmental disorder, X-linked 108

Summary

intellectual developmental disorder, X-linked 108 (MONDO:0026723) is a disease caused by SLC9A7 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: SLC9A7 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 22

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual developmental disorder, X-linked 108
Mondo ID	MONDO:0026723
OMIM	301024
DOID	DOID:0111844
UMLS	C5193009
MedGen	1680544
GARD	0025483
Is cancer (heuristic)	no

Also known as: intellectual developmental disorder, X-linked 108, X-linked recessive · MRX108

Data availability: 22 ClinVar variants · 5 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 108

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 disability, X-linked 106, intellectual disability, X-linked 107, intellectual developmental disorder, X-linked 110, intellectual developmental disorder, X-linked 111, 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

22 retrieved; paginated sample, class counts are floors:

15 uncertain significance, 3 benign, 3 likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1709052	NM_001111125.3(IQSEC2):c.1655_1667dup (p.Pro557fs)	IQSEC2	Likely pathogenic	criteria provided, single submitter
4277924	NM_001257291.2(SLC9A7):c.1147+2T>C	SLC9A7	Likely pathogenic	criteria provided, single submitter
548948	NM_001257291.2(SLC9A7):c.1543C>T (p.Leu515Phe)	SLC9A7	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1300133	NM_001257291.2(SLC9A7):c.1520G>A (p.Arg507His)	SLC9A7	Uncertain significance	criteria provided, single submitter
1679710	NM_001257291.2(SLC9A7):c.1447ATG[2] (p.Met485del)	SLC9A7	Uncertain significance	criteria provided, single submitter
1683727	NM_001257291.2(SLC9A7):c.1112G>A (p.Ser371Asn)	SLC9A7	Uncertain significance	criteria provided, single submitter
1683728	NM_001257291.2(SLC9A7):c.1350T>G (p.Phe450Leu)	SLC9A7	Uncertain significance	criteria provided, single submitter
1878558	NM_001257291.2(SLC9A7):c.988A>G (p.Ile330Val)	SLC9A7	Uncertain significance	criteria provided, single submitter
2436079	NM_001257291.2(SLC9A7):c.1999G>A (p.Gly667Arg)	SLC9A7	Uncertain significance	criteria provided, multiple submitters, no conflicts
2436080	NM_001257291.2(SLC9A7):c.1693G>A (p.Asp565Asn)	SLC9A7	Uncertain significance	criteria provided, multiple submitters, no conflicts
2436081	NM_001257291.2(SLC9A7):c.2171A>T (p.Asp724Val)	SLC9A7	Uncertain significance	criteria provided, multiple submitters, no conflicts
2436082	NM_001257291.2(SLC9A7):c.1667A>G (p.Gln556Arg)	SLC9A7	Uncertain significance	criteria provided, single submitter
2664831	NM_001257291.2(SLC9A7):c.706C>A (p.Leu236Ile)	SLC9A7	Uncertain significance	criteria provided, single submitter
2690037	NM_001257291.2(SLC9A7):c.460A>G (p.Thr154Ala)	SLC9A7	Uncertain significance	criteria provided, single submitter
3233321	NM_001257291.2(SLC9A7):c.2141G>A (p.Arg714Gln)	SLC9A7	Uncertain significance	criteria provided, single submitter
3901174	NM_001257291.2(SLC9A7):c.794-14G>A	SLC9A7	Uncertain significance	criteria provided, single submitter
4076182	NM_001257291.2(SLC9A7):c.733G>C (p.Asp245His)	SLC9A7	Uncertain significance	criteria provided, single submitter
944810	NM_001257291.2(SLC9A7):c.947A>T (p.Asp316Val)	SLC9A7	Uncertain significance	criteria provided, multiple submitters, no conflicts
1333125	NM_001257291.2(SLC9A7):c.1827C>T (p.Tyr609=)	SLC9A7	Benign	criteria provided, multiple submitters, no conflicts
1333126	NM_001257291.2(SLC9A7):c.1059A>G (p.Lys353=)	SLC9A7	Benign	criteria provided, single submitter
1333127	NM_001257291.2(SLC9A7):c.144G>C (p.Ala48=)	SLC9A7	Benign	criteria provided, multiple submitters, no conflicts
4072315	NM_001257291.2(SLC9A7):c.935C>A (p.Thr312Asn)	SLC9A7	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
SLC9A7	Strong	X-linked	intellectual developmental disorder, X-linked 108	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC9A7	Orphanet:777	X-linked non-syndromic intellectual disability
IQSEC2	Orphanet:217377	Microduplication Xp11.22p11.23 syndrome
IQSEC2	Orphanet:397933	Severe intellectual disability-progressive postnatal microcephaly-midline stereotypic hand movements syndrome
IQSEC2	Orphanet:819	Smith-Magenis syndrome

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
SLC9A7	HGNC:17123	ENSG00000065923	Q96T83	Sodium/hydrogen exchanger 7	gencc,clinvar
IQSEC2	HGNC:29059	ENSG00000124313	Q5JU85	IQ motif and SEC7 domain-containing protein 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC9A7	Sodium/hydrogen exchanger 7	Golgi Na(+), K(+)/(H+) antiporter.
IQSEC2	IQ motif and SEC7 domain-containing protein 2	Is a guanine nucleotide exchange factor for the ARF GTP-binding proteins.

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)
SLC9A7	Other/Unknown	no		NHE-6/7/9, NaH_exchanger, Cation/H_exchanger_TM
IQSEC2	Scaffold/PPI	no		Sec7_dom, PH_domain, PH-like_dom_sf

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
lateral globus pallidus	1
pons	1
superior vestibular nucleus	1
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC9A7	248	ubiquitous	marker	pons, lateral globus pallidus, superior vestibular nucleus
IQSEC2	236	ubiquitous	yes	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC9A7	1,487
IQSEC2	1,296

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
IQSEC2	Q5JU85	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SLC9A7	Q96T83	67.55

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
Sodium/Proton exchangers	1	1268.9×	0.003	SLC9A7
R-HSA-425393	1	129.8×	0.015	SLC9A7
SLC-mediated transmembrane transport	1	59.2×	0.023	SLC9A7
Transport of small molecules	1	25.1×	0.040	SLC9A7

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
obsolete regulation of Golgi lumen acidification	1	4213.0×	0.003	SLC9A7
positive regulation of long-term synaptic depression	1	936.2×	0.005	IQSEC2
regulation of pH	1	702.2×	0.005	SLC9A7
regulation of ARF protein signal transduction	1	443.5×	0.005	IQSEC2
regulation of neurotransmitter receptor localization to postsynaptic specialization membrane	1	443.5×	0.005	IQSEC2
positive regulation of synaptic transmission, glutamatergic	1	312.1×	0.005	IQSEC2
sodium ion import across plasma membrane	1	312.1×	0.005	SLC9A7
regulation of intracellular pH	1	300.9×	0.005	SLC9A7
positive regulation of synapse assembly	1	122.1×	0.012	IQSEC2
modulation of chemical synaptic transmission	1	91.6×	0.014	IQSEC2
monoatomic ion transport	1	78.0×	0.015	SLC9A7
potassium ion transmembrane transport	1	68.0×	0.016	SLC9A7
actin cytoskeleton organization	1	39.6×	0.025	IQSEC2

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
SLC9A7	0	0
IQSEC2	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	SLC9A7, IQSEC2

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)
SLC9A7	0	—
IQSEC2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.