Partial corpus callosum agenesis-cerebellar vermis hypoplasia with posterior fossa cysts syndrome

Summary

Partial corpus callosum agenesis-cerebellar vermis hypoplasia with posterior fossa cysts syndrome (MONDO:0018430) is a disease with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 2

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

Identifiers

Disease identifiers

Field	Value
Canonical name	partial corpus callosum agenesis-cerebellar vermis hypoplasia with posterior fossa cysts syndrome
Mondo ID	MONDO:0018430
Orphanet	401959
UMLS	C4750913
MedGen	1660429
GARD	0021707
Is cancer (heuristic)	no

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system malformation › partial corpus callosum agenesis-cerebellar vermis hypoplasia with posterior fossa cysts syndrome

Related subtypes (53): craniosynostosis-Dandy-Walker malformation-hydrocephalus syndrome, Aase-Smith syndrome, arachnoid cyst, 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, 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

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
KPNA6	Supportive	Autosomal recessive	partial corpus callosum agenesis-cerebellar vermis hypoplasia with posterior fossa cysts syndrome	3
KPNA7	Supportive	Autosomal recessive	partial corpus callosum agenesis-cerebellar vermis hypoplasia with posterior fossa cysts syndrome	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KPNA7	Orphanet:401959	Partial corpus callosum agenesis-cerebellar vermis hypoplasia with posterior fossa cysts syndrome

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
KPNA7	HGNC:21839	ENSG00000185467	A9QM74	Importin subunit alpha-8	gencc
KPNA6	HGNC:6399	ENSG00000025800	O60684	Importin subunit alpha-7	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KPNA7	Importin subunit alpha-8	Functions in nuclear protein import.
KPNA6	Importin subunit alpha-7	Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KPNA7	Other/Unknown	no		Armadillo, Importin-a_IBB, ARM-like
KPNA6	Other/Unknown	no		Armadillo, Importin-a_IBB, ARM-like

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
islet of Langerhans	1
male germ line stem cell (sensu Vertebrata) in testis	1
olfactory segment of nasal mucosa	1
buccal mucosa cell	1
nipple	1
oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KPNA7	52	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, olfactory segment of nasal mucosa, islet of Langerhans
KPNA6	291	ubiquitous	marker	buccal mucosa cell, nipple, oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KPNA6	3,451
KPNA7	2,123

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KPNA6	O60684	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
KPNA7	A9QM74	85.26

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 15. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
DNA Replication Pre-Initiation	1	158.6×	0.024	KPNA6
NS1 Mediated Effects on Host Pathways	1	142.8×	0.024	KPNA7
DNA Replication	1	119.0×	0.024	KPNA6
Maturation of DENV proteins	1	105.7×	0.024	KPNA7
Antimicrobial mechanism of IFN-stimulated genes	1	98.5×	0.024	KPNA7
Influenza Infection	1	87.8×	0.024	KPNA7
Assembly of the ORC complex at the origin of replication	1	82.8×	0.024	KPNA6
ISG15 antiviral mechanism	1	75.1×	0.024	KPNA7
Assembly of the pre-replicative complex	1	69.6×	0.024	KPNA6
Interferon Signaling	1	60.1×	0.025	KPNA7
Cytokine Signaling in Immune system	1	20.4×	0.066	KPNA7
Viral Infection Pathways	1	15.4×	0.080	KPNA7
Infectious disease	1	12.4×	0.091	KPNA7
Disease	1	6.5×	0.148	KPNA7
Immune System	1	6.5×	0.148	KPNA7

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
NLS-bearing protein import into nucleus	2	802.5×	2e-05	KPNA7, KPNA6
protein import into nucleus	2	144.0×	3e-04	KPNA7, KPNA6
entry of viral genome into host nucleus through nuclear pore complex via importin	1	2808.7×	0.002	KPNA6
positive regulation of viral life cycle	1	1203.7×	0.003	KPNA6
viral genome replication	1	561.7×	0.005	KPNA6
maternal process involved in female pregnancy	1	468.1×	0.005	KPNA6
blastocyst development	1	337.0×	0.006	KPNA7
positive regulation of cytokine production involved in inflammatory response	1	271.8×	0.006	KPNA6
epigenetic regulation of gene expression	1	191.5×	0.008	KPNA7
transcription by RNA polymerase II	1	35.3×	0.034	KPNA6
negative regulation of gene expression	1	34.5×	0.034	KPNA7
positive regulation of gene expression	1	19.4×	0.055	KPNA7
positive regulation of transcription by RNA polymerase II	1	7.4×	0.130	KPNA6

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KPNA6	1	2
KPNA7	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	KPNA6

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
KPNA6	6	Binding:6

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

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	KPNA6

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	KPNA6
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	KPNA7

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)
KPNA7	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.