intellectual disability, X-linked 106

Summary

intellectual disability, X-linked 106 (MONDO:0030907) is a disease caused by OGT (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: OGT (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 48

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual disability, X-linked 106
Mondo ID	MONDO:0030907
OMIM	300997
DOID	DOID:0080240
UMLS	C4478379
MedGen	1389156
GARD	0025656
Is cancer (heuristic)	no

Also known as: intellectual developmental disorder, X-linked 106, X-linked recessive · intellectual disability, X-linked 106 · mental retardation, X-linked 106 · MRX106 · X-linked mental retardation 106

Data availability: 48 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 › non-syndromic intellectual disability › non-syndromic X-linked intellectual disability › intellectual disability, X-linked 106

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 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

48 retrieved; paginated sample, class counts are floors:

35 uncertain significance, 6 pathogenic, 5 likely pathogenic, 2 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
428570	NM_181672.3(OGT):c.762G>T (p.Leu254Phe)	OGT	Pathogenic	no assertion criteria provided
428571	NM_181672.3(OGT):c.851G>C (p.Arg284Pro)	OGT	Pathogenic	no assertion criteria provided
428572	NM_181672.3(OGT):c.463-6T>G	OGT	Pathogenic	no assertion criteria provided
691611	NM_181672.3(OGT):c.1942A>T (p.Asn648Tyr)	OGT	Pathogenic	criteria provided, single submitter
804282	NM_181672.3(OGT):c.762G>C (p.Leu254Phe)	OGT	Pathogenic	no assertion criteria provided
804284	NM_181672.3(OGT):c.1016A>G (p.Glu339Gly)	OGT	Pathogenic	no assertion criteria provided
1804018	NM_181672.3(OGT):c.3139T>C (p.Ter1047Gln)	OGT	Likely pathogenic	criteria provided, single submitter
2582590	NM_181672.3(OGT):c.1529G>A (p.Ser510Asn)	OGT	Likely pathogenic	criteria provided, single submitter
3766444	NM_181672.3(OGT):c.1211C>T (p.Thr404Ile)	OGT	Likely pathogenic	criteria provided, single submitter
4531346	NM_181672.3(OGT):c.1711T>C (p.Ser571Pro)	OGT	Likely pathogenic	criteria provided, single submitter
689775	NM_181672.3(OGT):c.2795C>T (p.Thr932Ile)	OGT	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2962329	NM_181672.3(OGT):c.1125A>T (p.Gly375=)	OGT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
521426	NM_181672.3(OGT):c.307G>A (p.Gly103Arg)	OGT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3598424	NM_181672.3(OGT):c.34A>C (p.Thr12Pro)	LOC126863277	Uncertain significance	criteria provided, single submitter
4056691	NM_181672.3(OGT):c.7T>C (p.Ser3Pro)	LOC126863277	Uncertain significance	criteria provided, single submitter
1033236	NM_181672.3(OGT):c.420A>T (p.Glu140Asp)	OGT	Uncertain significance	criteria provided, single submitter
1285494	NM_181672.3(OGT):c.2501A>G (p.Gln834Arg)	OGT	Uncertain significance	criteria provided, single submitter
1334083	NM_181672.3(OGT):c.2693A>G (p.Asn898Ser)	OGT	Uncertain significance	criteria provided, multiple submitters, no conflicts
1334435	NM_181672.3(OGT):c.929C>T (p.Ala310Val)	OGT	Uncertain significance	no assertion criteria provided
1709135	NM_181672.3(OGT):c.596G>A (p.Cys199Tyr)	OGT	Uncertain significance	criteria provided, single submitter
1712281	NM_181672.3(OGT):c.3029A>G (p.Lys1010Arg)	OGT	Uncertain significance	criteria provided, multiple submitters, no conflicts
1805807	NM_181672.3(OGT):c.2723A>G (p.Lys908Arg)	OGT	Uncertain significance	criteria provided, single submitter
1992388	NM_181672.3(OGT):c.1664G>A (p.Arg555Gln)	OGT	Uncertain significance	criteria provided, single submitter
208705	NM_181672.3(OGT):c.775G>A (p.Ala259Thr)	OGT	Uncertain significance	criteria provided, single submitter
2434500	NM_181672.3(OGT):c.2855C>T (p.Ala952Val)	OGT	Uncertain significance	criteria provided, single submitter
2434501	NM_181672.3(OGT):c.2218G>A (p.Asp740Asn)	OGT	Uncertain significance	criteria provided, single submitter
2441772	NM_181672.3(OGT):c.1357C>G (p.Arg453Gly)	OGT	Uncertain significance	criteria provided, single submitter
2442184	NM_181672.3(OGT):c.140T>G (p.Leu47Arg)	OGT	Uncertain significance	criteria provided, single submitter
2582560	NM_181672.3(OGT):c.2429C>G (p.Thr810Ser)	OGT	Uncertain significance	criteria provided, multiple submitters, no conflicts
2637957	NM_181672.3(OGT):c.1709C>T (p.Thr570Ile)	OGT	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 0 · 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
OGT	Strong	X-linked	intellectual disability, X-linked 106	4

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
OGT	HGNC:8127	ENSG00000147162	O15294	UDP-N-acetylglucosamine–peptide N-acetylglucosaminyltransferase 110 kDa subunit	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
OGT	UDP-N-acetylglucosamine–peptide N-acetylglucosaminyltransferase 110 kDa subunit	Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in cytoplasmic and nuclear proteins resulting in their modification with a beta-linked N-acetylglucosamine (O-GlcNAc).

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
OGT	Enzyme (other)	yes	2.4.1.255	TPR-like_helical_dom_sf, TPR_rpt, OGT/SEC/SPY_C

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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
Brodmann (1909) area 23	1
middle temporal gyrus	1
skin of hip	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
OGT	295	ubiquitous	marker	middle temporal gyrus, Brodmann (1909) area 23, skin of hip

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
OGT	3,841

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
OGT	O15294	44

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 1 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
RIPK1-mediated regulated necrosis	1	456.8×	0.006	OGT
Regulation of necroptotic cell death	1	439.2×	0.006	OGT
Formation of WDR5-containing histone-modifying complexes	1	265.6×	0.006	OGT
UCH proteinases	1	124.1×	0.010	OGT
HATs acetylate histones	1	79.3×	0.013	OGT

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of non-canonical inflammasome complex assembly	1	16852.0×	0.002	OGT
positive regulation of transcription from RNA polymerase II promoter by glucose	1	3370.4×	0.004	OGT
regulation of Rac protein signal transduction	1	1872.4×	0.004	OGT
regulation of necroptotic process	1	1872.4×	0.004	OGT
regulation of insulin receptor signaling pathway	1	1685.2×	0.004	OGT
regulation of glycolytic process	1	1203.7×	0.004	OGT
regulation of gluconeogenesis	1	1123.5×	0.004	OGT
positive regulation of lipid biosynthetic process	1	887.0×	0.004	OGT
regulation of neurotransmitter receptor localization to postsynaptic specialization membrane	1	887.0×	0.004	OGT
positive regulation of proteolysis	1	802.5×	0.004	OGT
negative regulation of stem cell population maintenance	1	766.0×	0.004	OGT
regulation of synapse assembly	1	702.2×	0.004	OGT
negative regulation of proteasomal ubiquitin-dependent protein catabolic process	1	401.2×	0.006	OGT
positive regulation of stem cell population maintenance	1	343.9×	0.006	OGT
mitophagy	1	318.0×	0.006	OGT
response to nutrient	1	295.6×	0.006	OGT
positive regulation of TORC1 signaling	1	295.6×	0.006	OGT
negative regulation of protein ubiquitination	1	285.6×	0.006	OGT
hemopoiesis	1	267.5×	0.006	OGT
cellular response to glucose stimulus	1	267.5×	0.006	OGT
circadian regulation of gene expression	1	234.1×	0.006	OGT
response to insulin	1	230.8×	0.006	OGT
positive regulation of translation	1	227.7×	0.006	OGT
protein O-linked glycosylation	1	224.7×	0.006	OGT
negative regulation of transforming growth factor beta receptor signaling pathway	1	173.7×	0.008	OGT
protein processing	1	170.2×	0.008	OGT
positive regulation of cold-induced thermogenesis	1	163.6×	0.008	OGT
negative regulation of cell migration	1	111.6×	0.011	OGT
chromatin organization	1	99.1×	0.012	OGT
apoptotic process	1	28.7×	0.040	OGT

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
OGT	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	OGT

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
OGT	37	Binding:37

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
OGT	2.4.1.255	protein O-GlcNAc transferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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)
MOLIBRESIB	2	OGT

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	1	OGT
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.