autism, susceptibility to, X-linked 3

Summary

autism, susceptibility to, X-linked 3 (MONDO:0010342) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 81

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autism, susceptibility to, X-linked 3
Mondo ID	MONDO:0010342
OMIM	300496
UMLS	C1845336
MedGen	335161
Is cancer (heuristic)	no

Also known as: autism susceptibility, X-linked 3 · autism, susceptibility to, X-linked 3 · autism, susceptibility to, X-linked type 3 · AUTSX3

Data availability: 81 ClinVar variants.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › autism, susceptiblity to › autism, susceptibility to, X-linked 3

Related subtypes (25): autism, susceptibility to, X-linked 1, autism, susceptibility to, X-linked 2, autism, susceptibility to, X-linked 4, autism, susceptibility to, X-linked 5, epsilon-trimethyllysine hydroxylase deficiency, intellectual developmental disorder with autism and speech delay, autism, susceptibility to, 8, autism, susceptibility to, 3, autism, susceptibility to, 6, autism, susceptibility to, 7, autism, susceptibility to, 11, autism, susceptibility to, 12, autism, susceptibility to, 13, autism, susceptibility to, 9, autism, susceptibility to, 10, autism, susceptibility to, 15, autism, susceptibility to, 16, autism, susceptibility to, 17, intellectual developmental disorder with autism and macrocephaly, autism, susceptibility to, 19, autism, susceptibility to, 20, autism, susceptibility to, 14a, autism, susceptibility to, 14b, autism, susceptibility to, 1, autism, susceptibility to, 4

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

81 retrieved; paginated sample, class counts are floors:

17 uncertain significance, 16 benign, 14 pathogenic, 14 benign/likely benign, 7 pathogenic/likely pathogenic, 5 likely benign, 4 conflicting classifications of pathogenicity, 4 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
11811	NM_001110792.2(MECP2):c.509C>T (p.Thr170Met)	MECP2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
11814	NM_001110792.2(MECP2):c.352C>T (p.Arg118Trp)	MECP2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
11815	NM_001110792.2(MECP2):c.844C>T (p.Arg282Ter)	MECP2	Pathogenic	criteria provided, multiple submitters, no conflicts
11819	NM_001110792.2(MECP2):c.916C>T (p.Arg306Ter)	MECP2	Pathogenic	reviewed by expert panel
11823	NM_001110792.2(MECP2):c.455C>T (p.Ala152Val)	MECP2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
11824	NM_001110792.2(MECP2):c.952C>T (p.Arg318Cys)	MECP2	Pathogenic	reviewed by expert panel
11829	NM_001110792.2(MECP2):c.799C>T (p.Arg267Ter)	MECP2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
143369	NM_001110792.2(MECP2):c.1193_1233del (p.Leu398fs)	MECP2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
143406	NM_001110792.2(MECP2):c.1200_1243del (p.Pro400_Pro401insTer)	MECP2	Pathogenic	reviewed by expert panel
143562	NM_001110792.2(MECP2):c.437C>G (p.Ser146Cys)	MECP2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
143579	NM_001110792.2(MECP2):c.491C>G (p.Pro164Arg)	MECP2	Pathogenic	reviewed by expert panel
143664	NM_001110792.2(MECP2):c.732del (p.Lys245fs)	MECP2	Pathogenic	criteria provided, multiple submitters, no conflicts
143666	NM_001110792.2(MECP2):c.746dup (p.Gly250fs)	MECP2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
143702	NM_001110792.2(MECP2):c.844del (p.Arg282fs)	MECP2	Pathogenic	criteria provided, multiple submitters, no conflicts
143749	NM_001110792.2(MECP2):c.961C>T (p.Arg321Trp)	MECP2	Pathogenic	reviewed by expert panel
143754	NM_001110792.2(MECP2):c.1001C>T (p.Pro334Leu)	MECP2	Pathogenic	reviewed by expert panel
156068	NM_001110792.2(MECP2):c.414-3C>G	MECP2	Pathogenic	reviewed by expert panel
1684655	NM_001110792.2(MECP2):c.337_1247del911 (p.Pro113fs)	MECP2	Pathogenic	criteria provided, single submitter
3024298	NM_001110792.2(MECP2):c.450G>C (p.Leu150Phe)	MECP2	Pathogenic	criteria provided, single submitter
817508	NM_001110792.2(MECP2):c.331dup (p.Thr111fs)	MECP2	Pathogenic	criteria provided, multiple submitters, no conflicts
95202	NM_001110792.2(MECP2):c.842del (p.Gly281fs)	MECP2	Pathogenic	reviewed by expert panel
11844	NM_001110792.2(MECP2):c.490C>G (p.Pro164Ala)	MECP2	Likely pathogenic	reviewed by expert panel
3338074	NM_001110792.2(MECP2):c.17_27dup (p.Ser10fs)	MECP2	Likely pathogenic	no assertion criteria provided
3598189	NM_001110792.2(MECP2):c.934_935dup (p.Leu313fs)	MECP2	Likely pathogenic	criteria provided, single submitter
931417	NM_001110792.2(MECP2):c.1198_1206delinsACCAGCCCCC (p.Pro400fs)	MECP2	Likely pathogenic	criteria provided, single submitter
1166038	NM_001110792.2(MECP2):c.587C>G (p.Thr196Ser)	MECP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
143360	NM_001110792.2(MECP2):c.1191_1236del (p.Leu398fs)	MECP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
143593	NM_001110792.2(MECP2):c.515C>G (p.Thr172Ser)	MECP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
36494	NM_001110792.2(MECP2):c.934G>A (p.Val312Ile)	MECP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
133342	NM_001110792.2(MECP2):c.1483G>T (p.Glu495Ter)	MECP2	Uncertain significance	reviewed by expert panel

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 7 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MECP2	Orphanet:1762	Proximal Xq28 duplication syndrome
MECP2	Orphanet:209370	MECP2-related severe neonatal encephalopathy
MECP2	Orphanet:3077	X-linked intellectual disability-psychosis-macroorchidism syndrome
MECP2	Orphanet:3095	Atypical Rett syndrome
MECP2	Orphanet:536	Systemic lupus erythematosus
MECP2	Orphanet:777	X-linked non-syndromic intellectual disability
MECP2	Orphanet:778	Rett syndrome

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
MECP2	HGNC:6990	ENSG00000169057	P51608	Methyl-CpG-binding protein 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MECP2	Methyl-CpG-binding protein 2	Chromosomal protein that binds to methylated DNA.

Protein-family classification

Druggable: 0 · Difficult: 0 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MECP2	Other/Unknown	no		Methyl_CpG_DNA-bd, DNA-bd_dom_sf, Me_CpG-bd_MeCP2

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 10	1
paraflocculus	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MECP2	277	ubiquitous	marker	paraflocculus, Brodmann (1909) area 10, sural nerve

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MECP2	5,688

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MECP2	P51608	9

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. 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
Loss of MECP2 binding ability to 5hmC-DNA	1	11420.0×	1e-03	MECP2
MECP2 regulates transcription of genes involved in GABA signaling	1	3806.7×	1e-03	MECP2
Loss of phosphorylation of MECP2 at T308	1	2855.0×	1e-03	MECP2
Loss of MECP2 binding ability to 5mC-DNA	1	2855.0×	1e-03	MECP2
MECP2 regulates transcription factors	1	2284.0×	1e-03	MECP2
Loss of MECP2 binding ability to the NCoR/SMRT complex	1	1631.4×	0.001	MECP2
MECP2 regulates transcription of neuronal ligands	1	1427.5×	0.001	MECP2
MECP2 regulates neuronal receptors and channels	1	601.0×	0.002	MECP2
Regulation of MECP2 expression and activity	1	368.4×	0.003	MECP2
Nuclear events stimulated by ALK signaling in cancer	1	326.3×	0.003	MECP2
Transcriptional Regulation by MECP2	1	317.2×	0.003	MECP2

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
catecholamine secretion	1	16852.0×	0.001	MECP2
trans-synaptic signaling by BDNF	1	16852.0×	0.001	MECP2
cardiolipin metabolic process	1	8426.0×	0.001	MECP2
nervous system process involved in regulation of systemic arterial blood pressure	1	5617.3×	0.001	MECP2
biogenic amine metabolic process	1	5617.3×	0.001	MECP2
response to other organism	1	5617.3×	0.001	MECP2
proprioception	1	4213.0×	0.002	MECP2
glucocorticoid metabolic process	1	2808.7×	0.002	MECP2
inositol metabolic process	1	2407.4×	0.002	MECP2
positive regulation of microtubule nucleation	1	2106.5×	0.002	MECP2
negative regulation of smooth muscle cell differentiation	1	1872.4×	0.002	MECP2
regulation of respiratory gaseous exchange by nervous system process	1	1296.3×	0.003	MECP2
L-glutamine metabolic process	1	1296.3×	0.003	MECP2
startle response	1	1123.5×	0.003	MECP2
negative regulation of gene expression via chromosomal CpG island methylation	1	1053.2×	0.003	MECP2
genomic imprinting	1	991.3×	0.003	MECP2
glial cell proliferation	1	887.0×	0.003	MECP2
ventricular system development	1	842.6×	0.003	MECP2
neuron maturation	1	802.5×	0.003	MECP2
phosphatidylcholine metabolic process	1	802.5×	0.003	MECP2
negative regulation of blood vessel endothelial cell migration	1	732.7×	0.003	MECP2
positive regulation of glial cell proliferation	1	702.2×	0.003	MECP2
respiratory gaseous exchange by respiratory system	1	624.1×	0.003	MECP2
excitatory postsynaptic potential	1	443.5×	0.004	MECP2
behavioral fear response	1	432.1×	0.004	MECP2
long-term memory	1	421.3×	0.004	MECP2
dendrite development	1	391.9×	0.004	MECP2
sensory perception of pain	1	374.5×	0.004	MECP2
cerebellum development	1	358.6×	0.004	MECP2
visual learning	1	306.4×	0.005	MECP2

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
MECP2	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
MECP2	1	Binding:1

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	0
E	Difficult family or no structure, no drug	1	MECP2

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)
MECP2	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.