intellectual disability, X-linked 105

Summary

intellectual disability, X-linked 105 (MONDO:0010510) is a disease caused by USP27X (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: USP27X (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 20

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual disability, X-linked 105
Mondo ID	MONDO:0010510
OMIM	300984
DOID	DOID:0112036
UMLS	C4310816
MedGen	934783
GARD	0022697
Is cancer (heuristic)	no

Also known as: intellectual developmental disorder, X-linked 105, X-linked recessive · intellectual disability, X-linked 105 · intellectual disability, X-linked type 105 · mental retardation, X-linked 105 · mental retardation, X-linked type 105 · MRX105 · non-syndromic X-linked intellectual disability caused by mutation in USP27X · USP27X non-syndromic X-linked intellectual disability

Data availability: 20 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 105

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 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 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

20 retrieved; paginated sample, class counts are floors:

13 uncertain significance, 4 likely pathogenic, 2 pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1321965	NM_001145073.3(USP27X):c.106C>T (p.Gln36Ter)	USP27X	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
254684	NM_001145073.3(USP27X):c.1026_1030del (p.Ser342fs)	USP27X	Pathogenic	no assertion criteria provided
254685	NM_001145073.3(USP27X):c.1141T>C (p.Tyr381His)	USP27X	Pathogenic	no assertion criteria provided
2499534	NM_001145073.3(USP27X):c.1205dup (p.Ala403fs)	USP27X	Likely pathogenic	criteria provided, single submitter
2499535	NM_001145073.3(USP27X):c.937T>G (p.Phe313Val)	USP27X	Likely pathogenic	criteria provided, single submitter
2499536	NM_001145073.3(USP27X):c.394G>T (p.Glu132Ter)	USP27X	Likely pathogenic	criteria provided, single submitter
2684394	NM_001145073.3(USP27X):c.954del (p.Lys318fs)	USP27X	Likely pathogenic	criteria provided, single submitter
1031163	NM_001145073.3(USP27X):c.1157G>A (p.Arg386Gln)	USP27X	Uncertain significance	criteria provided, single submitter
1031164	NM_001145073.3(USP27X):c.94G>A (p.Glu32Lys)	USP27X	Uncertain significance	criteria provided, multiple submitters, no conflicts
1805819	NM_001145073.3(USP27X):c.1032G>C (p.Glu344Asp)	USP27X	Uncertain significance	criteria provided, single submitter
2499532	NM_001145073.3(USP27X):c.1211G>A (p.Ser404Asn)	USP27X	Uncertain significance	criteria provided, single submitter
2499533	NM_001145073.3(USP27X):c.431A>G (p.Tyr144Cys)	USP27X	Uncertain significance	criteria provided, single submitter
2499537	NM_001145073.3(USP27X):c.226G>A (p.Gly76Ser)	USP27X	Uncertain significance	criteria provided, single submitter
2499538	NM_001145073.3(USP27X):c.541A>G (p.Lys181Glu)	USP27X	Uncertain significance	criteria provided, single submitter
3362654	NM_001145073.3(USP27X):c.1265T>C (p.Val422Ala)	USP27X	Uncertain significance	criteria provided, single submitter
4080979	NM_001145073.3(USP27X):c.104A>G (p.His35Arg)	USP27X	Uncertain significance	criteria provided, single submitter
4081904	NM_001145073.3(USP27X):c.1085A>G (p.Asn362Ser)	USP27X	Uncertain significance	no assertion criteria provided
4531326	NM_001145073.3(USP27X):c.416CTC[1] (p.Pro140del)	USP27X	Uncertain significance	criteria provided, single submitter
4759462	NM_001145073.3(USP27X):c.453G>T (p.Trp151Cys)	USP27X	Uncertain significance	criteria provided, single submitter
931735	NM_001145073.3(USP27X):c.719_721del (p.Phe240del)	USP27X	Uncertain significance	criteria provided, multiple submitters, no conflicts

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
USP27X	Strong	X-linked	intellectual disability, X-linked 105	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
USP27X	Orphanet:777	X-linked non-syndromic intellectual disability

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
USP27X	HGNC:13486	ENSG00000273820	A6NNY8	Ubiquitin carboxyl-terminal hydrolase 27	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
USP27X	Ubiquitin carboxyl-terminal hydrolase 27	Deubiquitinase involved in innate antiviral immunity by mediating deubiquitination of CGAS and RIGI.

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
Protease	1	36.6×	0.027

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
USP27X	Protease	yes		Peptidase_C19_UCH, USP_CS, USP

Expression context

Cohort genes with no expression data: 0.

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
buccal mucosa cell	1
cerebellar vermis	1
endothelial cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
USP27X	236	ubiquitous	yes	buccal mucosa cell, endothelial cell, cerebellar vermis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
USP27X	1,369

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
USP27X	A6NNY8	78.52

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of type I interferon-mediated signaling pathway	1	842.6×	0.005	USP27X
protein K48-linked deubiquitination	1	648.1×	0.005	USP27X
protein K63-linked deubiquitination	1	624.1×	0.005	USP27X
protein deubiquitination	1	177.4×	0.013	USP27X
defense response to virus	1	69.3×	0.022	USP27X
protein stabilization	1	66.9×	0.022	USP27X
positive regulation of apoptotic process	1	56.7×	0.023	USP27X
proteolysis	1	34.2×	0.030	USP27X
innate immune response	1	33.6×	0.030	USP27X

Therapeutics

Drug target analysis

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

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
USP27X	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
USP27X	3	Binding:3

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

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	1	USP27X
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
USP27X	3	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.