intellectual disability, X-linked 107

Summary

intellectual disability, X-linked 107 (MONDO:0049222) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 16

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual disability, X-linked 107
Mondo ID	MONDO:0049222
OMIM	301013
DOID	DOID:0112054
UMLS	C4692652
MedGen	1639885
GARD	0022698
Is cancer (heuristic)	no

Also known as: intellectual developmental disorder, X-linked 107 · intellectual disability, X-linked 107 · mental retardation, X-linked 107 · MRX107

Data availability: 16 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 disability, X-linked 107

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 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

16 retrieved; paginated sample, class counts are floors:

8 uncertain significance, 3 pathogenic, 3 likely pathogenic, 2 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1526423	NM_022101.4(STEEP1):c.598C>T (p.Gln200Ter)	STEEP1	Pathogenic	no assertion criteria provided
523092	NM_022101.4(STEEP1):c.159_160insTA (p.Asp54Ter)	STEEP1	Pathogenic	no assertion criteria provided
976767	NM_022101.4(STEEP1):c.492AGAGGA[1] (p.Glu167_Glu168del)	STEEP1	Pathogenic	criteria provided, single submitter
2580340	GRCh37/hg19 Xq24(chrX:118544103-118676607)x0	SLC25A43	Likely pathogenic	criteria provided, single submitter
1698675	NM_022101.4(STEEP1):c.163del (p.Arg55fs)	STEEP1	Likely pathogenic	criteria provided, single submitter
2578554	NM_022101.4(STEEP1):c.79del (p.Leu27fs)	STEEP1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1029843	NM_022101.4(STEEP1):c.158G>T (p.Arg53Leu)	STEEP1	Uncertain significance	criteria provided, single submitter
1029844	NM_022101.4(STEEP1):c.44G>T (p.Arg15Leu)	STEEP1	Uncertain significance	criteria provided, single submitter
1803748	NM_022101.4(STEEP1):c.229_230del (p.Met77fs)	STEEP1	Uncertain significance	criteria provided, single submitter
2664017	NM_022101.4(STEEP1):c.494A>G (p.Glu165Gly)	STEEP1	Uncertain significance	no assertion criteria provided
3062102	NM_022101.4(STEEP1):c.169C>G (p.Arg57Gly)	STEEP1	Uncertain significance	criteria provided, single submitter
3376732	NM_022101.4(STEEP1):c.593G>A (p.Arg198Gln)	STEEP1	Uncertain significance	criteria provided, single submitter
3376835	NM_022101.4(STEEP1):c.287G>A (p.Cys96Tyr)	STEEP1	Uncertain significance	criteria provided, single submitter
4279749	NM_022101.4(STEEP1):c.244C>G (p.Pro82Ala)	STEEP1	Uncertain significance	criteria provided, single submitter
1255437	NM_022101.4(STEEP1):c.375C>T (p.Gly125=)	STEEP1	Benign	criteria provided, multiple submitters, no conflicts
1255438	NM_022101.4(STEEP1):c.-2T>C	STEEP1	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
STEEP1	Moderate	X-linked	intellectual disability, X-linked 107	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
STEEP1	Orphanet:777	X-linked non-syndromic intellectual disability

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
STEEP1	HGNC:26239	ENSG00000018610	Q9H5V9	STING ER exit protein	gencc,clinvar
SLC25A43	HGNC:30557	ENSG00000077713	Q8WUT9	Solute carrier family 25 member 43	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
STEEP1	STING ER exit protein	Molecular adapter that stimulates membrane curvature formation and subsequent endoplasmic reticulum exit site (ERES) establishment by recruiting PI3K complex I, leading to COPII vesicle-mediated transport.

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)
STEEP1	Other/Unknown	no		STEEP-like, STEEP1_dom
SLC25A43	Other/Unknown	no		MCP, MCP_transmembrane, MCP_dom_sf

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
oocyte	1
secondary oocyte	1
stromal cell of endometrium	1
esophagus squamous epithelium	1
jejunal mucosa	1
lower esophagus mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
STEEP1	240	ubiquitous	marker	oocyte, stromal cell of endometrium, secondary oocyte
SLC25A43	221	ubiquitous	marker	esophagus squamous epithelium, lower esophagus mucosa, jejunal mucosa

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
STEEP1	1,195
SLC25A43	1,062

Intra-cohort edges

A	B	Sources
SLC25A43	STEEP1	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
STEEP1	Q9H5V9	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SLC25A43	Q8WUT9	88.76

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
mRNA Splicing	1	109.8×	0.024	STEEP1
Processing of Capped Intron-Containing Pre-mRNA	1	82.2×	0.024	STEEP1
mRNA Splicing - Major Pathway	1	54.6×	0.024	STEEP1
Metabolism of RNA	1	41.7×	0.024	STEEP1

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
endoplasmic reticulum membrane organization	1	1203.7×	0.002	STEEP1
protein exit from endoplasmic reticulum	1	1053.2×	0.002	STEEP1
transmembrane transport	1	84.3×	0.015	SLC25A43
endoplasmic reticulum to Golgi vesicle-mediated transport	1	68.0×	0.015	STEEP1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
STEEP1	0	0
SLC25A43	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
STEEP1	6	Binding:6

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	STEEP1, SLC25A43

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)
STEEP1	6	—
SLC25A43	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.