Partington syndrome

Summary

Partington syndrome (MONDO:0010654) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 18
• Phenotypes (HPO): 13

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		2	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

13 HPO clinical features (Orphanet curated; top 13 by frequency):

HPO ID	Term	Frequency
HP:0000325	Triangular face	Very frequent (80-99%)
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0002451	Limb dystonia	Very frequent (80-99%)
HP:0000053	Macroorchidism	Frequent (30-79%)
HP:0001256	Intellectual disability, mild	Frequent (30-79%)
HP:0001260	Dysarthria	Frequent (30-79%)
HP:0001288	Gait disturbance	Frequent (30-79%)
HP:0002061	Lower limb spasticity	Frequent (30-79%)
HP:0002342	Intellectual disability, moderate	Frequent (30-79%)
HP:0000750	Delayed speech and language development	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0002353	EEG abnormality	Occasional (5-29%)
HP:0007380	Facial telangiectasia	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Partington syndrome
Mondo ID	MONDO:0010654
OMIM	309510
Orphanet	94083
DOID	DOID:14744
SNOMED CT	702412005
UMLS	C0796250
MedGen	163237
GARD	0004235
Is cancer (heuristic)	no

Also known as: intellectual disability, X-linked, syndromic 1 · intellectual disability, X-linked, with dystonic movements, ataxia, and seizures · intellectual disability-dystonic movements-ataxia-seizures syndrome · mental retardation, X-linked 36 · mental retardation, X-linked, syndromic 1 · mental retardation, X-linked, with dystonic movements, ataxia, and seizures · MRXS1 · Partington syndrome · Partington syndrome, X-linked recessive · Partington X-linked intellectual disability syndrome · Partington X-linked mental retardation syndrome · Partington-Mulley syndrome · PRTS · X-linked intellectual disability-dystonia-dysarthria syndrome

Data availability: 18 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › neurodevelopmental disorder › intellectual disability › syndromic intellectual disability › X-linked syndromic intellectual disability › Partington syndrome

Related subtypes (80): X-linked intellectual disability-psychosis-macroorchidism syndrome, X-linked intellectual disability-plagiocephaly syndrome, intellectual disability, X-linked 49, MEHMO syndrome, syndromic X-linked intellectual disability 7, syndromic X-linked intellectual disability Shashi type, syndromic X-linked intellectual disability Lubs type, syndromic X-linked intellectual disability Abidi type, syndromic X-linked intellectual disability Siderius type, X-linked intellectual disability, Cabezas type, X-linked intellectual disability, Stocco dos Santos type, X-linked intellectual disability-cubitus valgus-dysmorphism syndrome, corpus callosum agenesis-intellectual disability-coloboma-micrognathia syndrome, X-linked intellectual disability-cerebellar hypoplasia syndrome, Allan-Herndon-Dudley syndrome, syndromic X-linked intellectual disability Claes-Jensen type, X-linked intellectual disability-retinitis pigmentosa syndrome, syndromic X-linked intellectual disability 14, syndromic X-linked intellectual disability 94, intellectual disability, X-linked syndromic, Turner type, syndromic X-linked intellectual disability Shrimpton type, X-linked intellectual disability-craniofacioskeletal syndrome, syndromic X-linked intellectual disability Raymond type, syndromic X-linked intellectual disability 17, syndromic X-linked intellectual disability Nascimento type, syndromic X-linked intellectual disability Chudley-Schwartz type, X-linked intellectual disability-cardiomegaly-congestive heart failure syndrome, X-linked intellectual disability, Cantagrel type, X-linked intellectual disability-short stature-overweight syndrome, intellectual disability, X-linked, syndromic 33, syndromic X-linked intellectual disability 34, intellectual disability, X-linked 99, syndromic, female-restricted, intellectual disability, X-linked, syndromic, Bain type, Borjeson-Forssman-Lehmann syndrome, Coffin-Lowry syndrome, syndromic X-linked intellectual disability 5, X-linked intellectual disability-seizures-psoriasis syndrome, Renpenning syndrome, syndromic X-linked intellectual disability 12, severe X-linked intellectual disability, Gustavson type, syndromic X-linked intellectual disability Snyder type, Wilson-Turner syndrome, Prieto syndrome, skeletal dysplasia-intellectual disability syndrome, X-linked intellectual disability-spastic quadriparesis syndrome, early-onset parkinsonism-intellectual disability syndrome, X-linked intellectual disability, Schimke type, X-linked intellectual disability, Cilliers type, X-linked intellectual disability, van Esch type, X-linked intellectual disability-epilepsy syndrome, ATR-X-related syndrome, X-linked intellectual disability-hypogonadism-ichthyosis-obesity-short stature syndrome, X-linked intellectual disability, Schutz type, X-linked intellectual disability-hypotonia-movement disorder syndrome, X-linked intellectual disability with isolated growth hormone deficiency, X-linked intellectual disability-hypogammaglobulinemia-progressive neurological deterioration syndrome, X-linked intellectual disability-precocious puberty-obesity syndrome, X-linked intellectual disability-epilepsy-progressive joint contractures-dysmorphism syndrome, X-linked intellectual disability-macrocephaly-macroorchidism syndrome, X-linked intellectual disability, Pai type, X-linked intellectual disability, Seemanova type, X-linked intellectual disability, Stevenson type, X-linked intellectual disability, Stoll type, X-linked intellectual disability-acromegaly-hyperactivity syndrome, X-linked intellectual disability-corpus callosum agenesis-spastic quadriparesis syndrome, fried syndrome, X-linked intellectual disability-ataxia-apraxia syndrome, intellectual developmental disorder, X-linked, syndromic, Pilorge type, Paganini-Miozzo syndrome, intellectual developmental disorder, X-linked, syndromic, Hackmann-Di Donato type, intellectual disability, X-linked, syndromic, 35, intellectual disability, X-linked, syndromic, Houge type, MED12-related intellectual disability syndrome, NAA10-related syndrome, ATP6AP2-related disorder, X-linked intellectual disability with hypopituitarism, SOX3-related X-linked pituitary hormone deficiency with or without intellectual developmental disorder, intellectual developmental disorder, X-linked, syndromic, with pigmentary mosaicism and coarse facies, intellectual developmental disorder, X-linked, syndromic 37, CASK-related intellectual disability

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

18 retrieved; paginated sample, class counts are floors:

7 uncertain significance, 4 pathogenic, 3 conflicting classifications of pathogenicity, 2 pathogenic/likely pathogenic, 1 benign/likely benign, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
11188	NM_139058.3(ARX):c.1058C>T (p.Pro353Leu)	ARX	Pathogenic	criteria provided, multiple submitters, no conflicts
1494703	NM_139058.3(ARX):c.994C>G (p.Arg332Gly)	ARX	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1526401	NM_139058.3(ARX):c.26dup (p.Cys10fs)	ARX	Pathogenic	criteria provided, single submitter
4796607	NM_139058.3(ARX):c.969dup (p.Leu324fs)	ARX	Pathogenic	criteria provided, single submitter
11186	NM_139058.3(ARX):c.306GGC[17] (p.Ala109_Ala115dup)	LOC109610631	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
96455	NM_139058.3(ARX):c.441_464dup (p.Ala148_Ala155dup)	LOC109610631	Pathogenic	criteria provided, multiple submitters, no conflicts
4294490	NM_139058.3(ARX):c.433_448del (p.Ala145fs)	ARX	Likely pathogenic	criteria provided, single submitter
11187	NM_139058.3(ARX):c.428_451dup (p.Gly143_Ala150dup)	ARX	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
234531	NM_139058.3(ARX):c.1170C>T (p.Gly390=)	ARX	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
581240	NM_139058.3(ARX):c.187G>A (p.Ala63Thr)	ARX	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1328434	NM_139058.3(ARX):c.1495G>A (p.Ala499Thr)	ARX	Uncertain significance	no assertion criteria provided
187818	NM_139058.3(ARX):c.260G>C (p.Arg87Pro)	ARX	Uncertain significance	criteria provided, single submitter
2500058	NM_139058.3(ARX):c.229G>A (p.Ala77Thr)	ARX	Uncertain significance	criteria provided, multiple submitters, no conflicts
3338775	NM_139058.3(ARX):c.650C>T (p.Ala217Val)	ARX	Uncertain significance	criteria provided, multiple submitters, no conflicts
473008	NM_139058.3(ARX):c.306GGC[4] (p.Ala110_Ala115del)	ARX	Uncertain significance	criteria provided, multiple submitters, no conflicts
588454	NM_139058.3(ARX):c.1450C>T (p.Leu484Phe)	ARX	Uncertain significance	criteria provided, multiple submitters, no conflicts
818170	NM_139058.3(ARX):c.441_455dup (p.Ala151_Ala155dup)	LOC109610631	Uncertain significance	criteria provided, multiple submitters, no conflicts
157762	NM_139058.3(ARX):c.807C>T (p.Ala269=)	ARX	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 16 · Orphanet: 8 · 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
ARX	Supportive	X-linked	Partington syndrome	16

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ARX	Orphanet:1934	Early infantile developmental and epileptic encephalopathy
ARX	Orphanet:2508	Corpus callosum agenesis-abnormal genitalia syndrome
ARX	Orphanet:3175	X-linked spasticity-intellectual disability-epilepsy syndrome
ARX	Orphanet:364063	Infantile epileptic-dyskinetic encephalopathy
ARX	Orphanet:452	X-linked lissencephaly with abnormal genitalia
ARX	Orphanet:697160	Infantile epileptic spasms syndrome
ARX	Orphanet:777	X-linked non-syndromic intellectual disability
ARX	Orphanet:94083	Partington 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
ARX	HGNC:18060	ENSG00000004848	Q96QS3	Homeobox protein ARX	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ARX	Homeobox protein ARX	Transcription factor.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ARX	Transcription factor	no		HD, OAR_dom, Homeodomain-like_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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left ovary	1
ovary	1
right ovary	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ARX	162	broad	marker	left ovary, ovary, right ovary

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ARX	758

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ARX	Q96QS3	56.51

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
embryonic olfactory bulb interneuron precursor migration	1	8426.0×	0.001	ARX
cerebral cortex tangential migration	1	4213.0×	0.001	ARX
epithelial cell fate commitment	1	4213.0×	0.001	ARX
globus pallidus development	1	3370.4×	0.001	ARX
lipid digestion	1	3370.4×	0.001	ARX
cerebral cortex GABAergic interneuron migration	1	2808.7×	0.001	ARX
positive regulation of organ growth	1	1404.3×	0.002	ARX
cell proliferation in forebrain	1	1296.3×	0.002	ARX
regulation of epithelial cell proliferation	1	936.2×	0.002	ARX
neuron fate commitment	1	802.5×	0.002	ARX
organ growth	1	732.7×	0.002	ARX
neuron development	1	255.3×	0.006	ARX
axon guidance	1	90.6×	0.014	ARX
positive regulation of gene expression	1	38.7×	0.031	ARX
negative regulation of transcription by RNA polymerase II	1	17.7×	0.064	ARX
positive regulation of transcription by RNA polymerase II	1	14.9×	0.071	ARX
regulation of transcription by RNA polymerase II	1	11.7×	0.086	ARX

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 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
ARX	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	ARX

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)
ARX	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.