Congenital velopharyngeal incompetence

Summary

Congenital velopharyngeal incompetence (MONDO:0008180) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 2
• Phenotypes (HPO): 5

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		37	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

5 HPO clinical features (Orphanet curated; top 5 by frequency):

HPO ID	Term	Frequency
HP:0000174	Abnormal palate morphology	Very frequent (80-99%)
HP:0000220	Velopharyngeal insufficiency	Very frequent (80-99%)
HP:0000600	Abnormality of the pharynx	Very frequent (80-99%)
HP:0001608	Abnormality of the voice	Very frequent (80-99%)
HP:0000365	Hearing impairment	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital velopharyngeal incompetence
Mondo ID	MONDO:0008180
MeSH	D014681
OMIM	167500
Orphanet	2291
ICD-11	158386351
UMLS	C0042454
MedGen	52992
GARD	0005470
Is cancer (heuristic)	no

Data availability: 2 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › otorhinolaryngologic disease › congenital velopharyngeal incompetence

Related subtypes (39): bifid nose, autoimmune disease of ear, nose and throat, nasal disorder, atresia of external auditory canal and conductive deafness, external auditory canal atresia-vertical talus-hypertelorism syndrome, laryngeal abductor paralysis, larynx atresia, microtia, congenital tracheal stenosis, laryngeal neuroendocrine neoplasm, arrhinia, laryngotracheal angioma, epignathus, nasolacrimal duct cyst, polyrrhinia, supernumerary nostril, proboscis lateralis, nasal glial heterotopia, nasal ganglioglioma, nasal encephalocele, isolated congenital syngnathia, cysts and fistulae of the face and oral cavity, isolated congenital nasal pyriform aperture stenosis, congenital nasal pyriform aperture stenosis with holoprosencephaly, middle ear anomaly, idiopathic bilateral vestibulopathy, mal de Debarquement, juvenile nasopharyngeal angiofibroma, tracheal agenesis, semicircular canal dehiscence syndrome, hereditary otorhinolaryngologic disease, supratip dysplasia, recurrent respiratory papillomatosis, silent sinus syndrome, anotia, congenital tracheomalacia, disorder of pharynx, disorder of ear, lip and oral cavity squamous cell carcinoma

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

2 retrieved; paginated sample, class counts are floors:

1 uncertain significance, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
523273	GRCh37/hg19 22q11.21(chr22:18894835-20311763)	C22orf39	Pathogenic	criteria provided, single submitter
267914	46;XY;t(9;14)(p21;q12)dn		Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

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

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
C22orf39	HGNC:27012	ENSG00000242259	Q6P5X5	Synaptic plasticity regulator PANTS	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
C22orf39	Synaptic plasticity regulator PANTS	Negatively regulates long-term potentiation and modulates adult synaptic plasticity.

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)
C22orf39	Other/Unknown	no		Pants/Emi1-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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
gastrocnemius	1
hindlimb stylopod muscle	1
muscle of leg	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
C22orf39	250	tissue_specific	marker	gastrocnemius, muscle of leg, hindlimb stylopod muscle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
C22orf39	679

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
C22orf39	Q6P5X5	89.97

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
negative regulation of long-term synaptic potentiation	1	1296.3×	0.002	C22orf39
regulation of synaptic plasticity	1	259.3×	0.004	C22orf39

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
C22orf39	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	C22orf39

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)
C22orf39	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.