Arachnoid cyst

Summary

Arachnoid cyst (MONDO:0008813) is a disease with 2 cohort genes.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 2
• ClinVar variants: 3
• Phenotypes (HPO): 67

Clinical features

Signs & symptoms

Clinical features (HPO)

67 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0002315	Headache	Frequent (30-79%)
HP:0010576	Intracranial cystic lesion	Frequent (30-79%)
HP:0032070	Leptomeningeal enhancement	Frequent (30-79%)
HP:0000020	Urinary incontinence	Occasional (5-29%)
HP:0000238	Hydrocephalus	Occasional (5-29%)
HP:0000508	Ptosis	Occasional (5-29%)
HP:0000622	Blurred vision	Occasional (5-29%)
HP:0000639	Nystagmus	Occasional (5-29%)
HP:0000651	Diplopia	Occasional (5-29%)
HP:0000716	Depression	Occasional (5-29%)
HP:0000734	Disinhibition	Occasional (5-29%)
HP:0000737	Irritability	Occasional (5-29%)
HP:0000745	Diminished motivation	Occasional (5-29%)
HP:0000818	Abnormality of the endocrine system	Occasional (5-29%)
HP:0000933	Posterior fossa cyst at the fourth ventricle	Occasional (5-29%)
HP:0001123	Visual field defect	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001269	Hemiparesis	Occasional (5-29%)
HP:0001288	Gait disturbance	Occasional (5-29%)
HP:0001293	Cranial nerve compression	Occasional (5-29%)
HP:0001317	Abnormal cerebellum morphology	Occasional (5-29%)
HP:0001350	Slurred speech	Occasional (5-29%)
HP:0002018	Nausea	Occasional (5-29%)
HP:0002027	Abdominal pain	Occasional (5-29%)
HP:0002138	Subarachnoid hemorrhage	Occasional (5-29%)
HP:0002176	Spinal cord compression	Occasional (5-29%)
HP:0002273	Tetraparesis	Occasional (5-29%)
HP:0002308	Chiari malformation	Occasional (5-29%)
HP:0002321	Vertigo	Occasional (5-29%)
HP:0002354	Memory impairment	Occasional (5-29%)
HP:0002385	Paraparesis	Occasional (5-29%)
HP:0002460	Distal muscle weakness	Occasional (5-29%)
HP:0002540	Inability to walk	Occasional (5-29%)
HP:0002839	Urinary bladder sphincter dysfunction	Occasional (5-29%)
HP:0002936	Distal sensory impairment	Occasional (5-29%)
HP:0003401	Paresthesia	Occasional (5-29%)
HP:0003418	Back pain	Occasional (5-29%)
HP:0003698	Difficulty standing	Occasional (5-29%)
HP:0004396	Poor appetite	Occasional (5-29%)
HP:0005324	Disturbance of facial expression	Occasional (5-29%)
HP:0006824	Cranial nerve paralysis	Occasional (5-29%)
HP:0007086	Social and occupational deterioration	Occasional (5-29%)
HP:0007291	Posterior fossa cyst	Occasional (5-29%)
HP:0007340	Lower limb muscle weakness	Occasional (5-29%)
HP:0009745	Spinalarachnoid cyst	Occasional (5-29%)
HP:0010303	Abnormal spinal meningeal morphology	Occasional (5-29%)
HP:0010628	Facial palsy	Occasional (5-29%)
HP:0011499	Mydriasis	Occasional (5-29%)
HP:0011868	Sciatica	Occasional (5-29%)
HP:0012246	Oculomotor nerve palsy	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	arachnoid cyst
Mondo ID	MONDO:0008813
MeSH	D016080
Orphanet	2356
NCIT	C3455
SNOMED CT	33595009
UMLS	C0078981
MedGen	86860
GARD	0000017
MedDRA	10049005
Is cancer (heuristic)	no

Also known as: arachnoid cysts

Data availability: 3 ClinVar variants.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system malformation › arachnoid cyst

Related subtypes (53): craniosynostosis-Dandy-Walker malformation-hydrocephalus syndrome, Aase-Smith syndrome, facial dysmorphism-macrocephaly-myopia-Dandy-Walker malformation syndrome, Dandy-Walker malformation-postaxial polydactyly syndrome, cervical hypertrichosis-peripheral neuropathy syndrome, Joubert syndrome with oculorenal defect, NPHP3-related Meckel-like syndrome, orofaciodigital syndrome type 6, X-linked intellectual disability-cerebellar hypoplasia syndrome, syndromic X-linked intellectual disability Najm type, X-linked cerebral-cerebellar-coloboma syndrome syndrome, syndromic X-linked intellectual disability 5, holoprosencephaly-hypokinesia-congenital contractures syndrome, aprosencephaly cerebellar dysgenesis, Gomez-Lopez-Hernandez syndrome, PHACE syndrome, B4GALT1-congenital disorder of glycosylation, permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome, hypomyelinating leukodystrophy 8 with or without oligodontia and-or hypogonadotropic hypogonadism, pontine tegmental cap dysplasia, ataxia - intellectual disability - oculomotor apraxia - cerebellar cysts syndrome, cerebellar-facial-dental syndrome, lethal fetal cerebrorenogenitourinary agenesis/hypoplasia syndrome, autosomal recessive spinocerebellar ataxia 20, SLC39A8-CDG, severe intellectual disability-corpus callosum agenesis-facial dysmorphism-cerebellar ataxia syndrome, TELO2-related intellectual disability-neurodevelopmental disorder, isolated cerebellar vermis hypoplasia, cerebral gigantism-jaw cysts syndrome, holoprosencephaly-caudal dysgenesis syndrome, Joubert syndrome with ocular defect, macrocephaly-short stature-paraplegia syndrome, glioependymal/ependymal cyst, isolated cerebellar vermis agenesis, isolated unilateral hemispheric cerebellar hypoplasia, isolated bilateral hemispheric cerebellar hypoplasia, Hoyeraal-Hreidarsson syndrome, neural tube defect, partial corpus callosum agenesis-cerebellar vermis hypoplasia with posterior fossa cysts syndrome, X-linked intellectual disability-cerebellar hypoplasia-spondylo-epiphyseal dysplasia syndrome, tubulinopathy-associated dysgyria, global developmental delay-visual anomalies-progressive cerebellar atrophy-truncal hypotonia syndrome, rhombencephalosynapsis, Lhermitte-Duclos disease, Ritscher-Schinzel syndrome, spinal muscular atrophy-Dandy-Walker malformation-cataracts syndrome, cystic malformation of the posterior fossa, pontocerebellar hypoplasia, congenital labioscrotal agenesis-cerebellar malformation-corneal dystrophy-facial dysmorphism syndrome, childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder, overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes, hereditary cerebral malformation, isolated arhinencephaly

Subtypes (2): spinal intradural arachnoid cysts, intracranial arachoid cyst

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

3 retrieved; paginated sample, class counts are floors:

1 pathogenic/likely pathogenic, 1 uncertain significance, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1077119	NM_139058.3(ARX):c.994C>T (p.Arg332Cys)	ARX	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
983221	NM_022474.4(PALS1):c.1289A>G (p.Glu430Gly)	PALS1	Pathogenic	criteria provided, single submitter
267865	46;XY;t(2;11)(q31;q13.5)pat		Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 9 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

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
PALS1	Orphanet:528084	Non-specific 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
ARX	HGNC:18060	ENSG00000004848	Q96QS3	Homeobox protein ARX	clinvar
PALS1	HGNC:18669	ENSG00000072415	Q8N3R9	Protein PALS1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ARX	Homeobox protein ARX	Transcription factor.
PALS1	Protein PALS1	Plays a role in tight junction biogenesis and in the establishment of cell polarity in epithelial cells.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.5

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
Kinase	1	13.9×	0.142
Transcription factor	1	4.1×	0.228

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ARX	Transcription factor	no		HD, OAR_dom, Homeodomain-like_sf
PALS1	Kinase	yes		SH3_domain, PDZ, L27_dom

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
left ovary	1
ovary	1
right ovary	1
germinal epithelium of ovary	1
jejunal mucosa	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ARX	162	broad	marker	left ovary, ovary, right ovary
PALS1	272	ubiquitous	marker	jejunal mucosa, ventricular zone, germinal epithelium of ovary

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PALS1	2,825
ARX	758

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PALS1	Q8N3R9	9

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ARX	Q96QS3	56.51

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
SARS-CoV-1 targets PDZ proteins in cell-cell junction	1	11420.0×	3e-04	PALS1
SARS-CoV-2 targets PDZ proteins in cell-cell junction	1	2284.0×	7e-04	PALS1
Tight junction interactions	1	368.4×	0.003	PALS1

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
protein localization to myelin sheath abaxonal region	1	8426.0×	0.002	PALS1
embryonic olfactory bulb interneuron precursor migration	1	4213.0×	0.002	ARX
establishment or maintenance of polarity of embryonic epithelium	1	2808.7×	0.002	PALS1
cerebral cortex tangential migration	1	2106.5×	0.002	ARX
epithelial cell fate commitment	1	2106.5×	0.002	ARX
globus pallidus development	1	1685.2×	0.002	ARX
lipid digestion	1	1685.2×	0.002	ARX
cerebral cortex GABAergic interneuron migration	1	1404.3×	0.003	ARX
myelin assembly	1	936.2×	0.003	PALS1
morphogenesis of an epithelial sheet	1	842.6×	0.003	PALS1
peripheral nervous system myelin maintenance	1	766.0×	0.003	PALS1
generation of neurons	1	766.0×	0.003	PALS1
positive regulation of organ growth	1	702.2×	0.003	ARX
cell proliferation in forebrain	1	648.1×	0.003	ARX
regulation of epithelial cell proliferation	1	468.1×	0.004	ARX
regulation of transforming growth factor beta receptor signaling pathway	1	401.2×	0.004	PALS1
central nervous system neuron development	1	401.2×	0.004	PALS1
neuron fate commitment	1	401.2×	0.004	ARX
organ growth	1	366.4×	0.004	ARX
establishment or maintenance of epithelial cell apical/basal polarity	1	290.6×	0.005	PALS1
neuron development	1	127.7×	0.011	ARX
cerebral cortex development	1	102.8×	0.013	PALS1
protein localization to plasma membrane	1	54.4×	0.023	PALS1
axon guidance	1	45.3×	0.027	ARX
gene expression	1	39.9×	0.029	PALS1
positive regulation of gene expression	1	19.4×	0.057	ARX
negative regulation of transcription by RNA polymerase II	1	8.9×	0.118	ARX
positive regulation of transcription by RNA polymerase II	1	7.4×	0.135	ARX
regulation of transcription by RNA polymerase II	1	5.8×	0.164	ARX

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 2 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
PALS1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	1	PALS1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	ARX

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)
ARX	0	—
PALS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.