Choanal atresia

Summary

Choanal atresia (MONDO:0012155) is a disease with 2 cohort genes and 9 clinical trials. Top therapeutic interventions include gallium ga 68 gozetotide.

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Cohort genes: 2
• ClinVar variants: 2
• Phenotypes (HPO): 16
• Clinical trials: 9

Clinical features

Epidemiology

Prevalence records

17 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000		Europe	Validated
Prevalence at birth	1-9 / 100 000	8.6	Europe	Validated
Prevalence at birth	1-9 / 100 000	9.8	Austria	Validated
Prevalence at birth	1-5 / 10 000	14.6	Belgium	Validated
Prevalence at birth	1-5 / 10 000	21.3	Denmark	Validated
Prevalence at birth	1-5 / 10 000	15.7	France	Validated
Prevalence at birth	1-9 / 100 000	5.9	Germany	Validated
Prevalence at birth	1-5 / 10 000	10	Hungary	Validated
Prevalence at birth	1-9 / 100 000	7.2	Ireland	Validated
Prevalence at birth	1-9 / 100 000	5.7	Italy	Validated
Prevalence at birth	1-5 / 10 000	11.7	Netherlands	Validated
Prevalence at birth	1-9 / 100 000	4.9	Norway	Validated
Prevalence at birth	1-9 / 100 000	2.2	Poland	Validated
Prevalence at birth	1-9 / 100 000	6.3	Spain	Validated
Prevalence at birth	1-5 / 10 000	12.6	Switzerland	Validated
Prevalence at birth	1-9 / 100 000	8.9	United Kingdom	Validated
Prevalence at birth	1-9 / 100 000	3.2	Ukraine	Validated

Signs & symptoms

Clinical features (HPO)

16 HPO clinical features (Orphanet curated; top 16 by frequency):

HPO ID	Term	Frequency
HP:0001742	Nasal congestion	Frequent (30-79%)
HP:0011109	Chronic sinusitis	Frequent (30-79%)
HP:0031416	Abnormal nasal mucus secretion	Frequent (30-79%)
HP:0000961	Cyanosis	Occasional (5-29%)
HP:0001363	Craniosynostosis	Occasional (5-29%)
HP:0001601	Laryngomalacia	Occasional (5-29%)
HP:0001607	Subglottic stenosis	Occasional (5-29%)
HP:0002098	Respiratory distress	Occasional (5-29%)
HP:0002205	Recurrent respiratory infections	Occasional (5-29%)
HP:0002779	Tracheomalacia	Occasional (5-29%)
HP:0002781	Upper airway obstruction	Occasional (5-29%)
HP:0005321	Mandibulofacial dysostosis	Occasional (5-29%)
HP:0011968	Feeding difficulties	Occasional (5-29%)
HP:0030215	Inappropriate crying	Occasional (5-29%)
HP:0030842	Choking episodes	Occasional (5-29%)
HP:0010442	Polydactyly	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	choanal atresia
Mondo ID	MONDO:0012155
MeSH	D002754
OMIM	608911
Orphanet	137914
DOID	DOID:9574
ICD-10-CM	Q30.0
ICD-11	2099486655
SNOMED CT	204508009
UMLS	C0008297
MedGen	3395
GARD	0016951
MedDRA	10008587
Is cancer (heuristic)	no

Also known as: atresia of nares · choanal atresia, POSTERIOR · PCA

Data availability: 2 ClinVar variants.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › otorhinolaryngologic disease › nasal disorder › nasal cavity disorder › choanal atresia

Related subtypes (4): rhinitis, nasal cavity neoplasm, nasal cavity polyp, Binder syndrome

Subtypes (2): choanal atresia, unilateral, choanal atresia, bilateral

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 likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
523522	NM_017780.4(CHD7):c.2867C>A (p.Ser956Ter)	CHD7	Likely pathogenic	criteria provided, single submitter
977143	NM_003482.4(KMT2D):c.10624C>G (p.Leu3542Val)	KMT2D	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 6 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CHD7	Orphanet:138	CHARGE syndrome
CHD7	Orphanet:39041	Omenn syndrome
CHD7	Orphanet:432	Normosmic congenital hypogonadotropic hypogonadism
CHD7	Orphanet:478	Kallmann syndrome
KMT2D	Orphanet:2322	Kabuki syndrome
KMT2D	Orphanet:589856	Choanal atresia-athelia-hypothyroidism-delayed puberty-short stature 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
CHD7	HGNC:20626	ENSG00000171316	Q9P2D1	ATP-dependent chromatin remodeler CHD7	clinvar
KMT2D	HGNC:7133	ENSG00000167548	O14686	Histone-lysine N-methyltransferase 2D	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CHD7	ATP-dependent chromatin remodeler CHD7	ATP-dependent chromatin-remodeling factor, slides nucleosomes along DNA; nucleosome sliding requires ATP.
KMT2D	Histone-lysine N-methyltransferase 2D	Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of ‘Lys-4’ of histone H3 (H3K4).

Protein-family classification

Druggable: 0 · Difficult: 1 · 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
Transcription factor	1	4.1×	0.455
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CHD7	Other/Unknown	no		SNF2_N, Chromo/chromo_shadow_dom, Helicase_C-like
KMT2D	Transcription factor	no		SET_dom, Znf_RING, Znf_PHD

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
sural nerve	2
cerebellar vermis	1
secondary oocyte	1
buccal mucosa cell	1
medial globus pallidus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CHD7	269	ubiquitous	marker	secondary oocyte, cerebellar vermis, sural nerve
KMT2D	272	ubiquitous	marker	buccal mucosa cell, medial globus pallidus, sural nerve

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CHD7	4,819
KMT2D	3,223

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KMT2D	O14686	11
CHD7	Q9P2D1	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 24. 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
Loss of Function of KMT2D in MLL4 Complex Formation in Kabuki Syndrome	1	1142.0×	0.021	KMT2D
Activation of HOX genes during differentiation	1	219.6×	0.030	KMT2D
Formation of WDR5-containing histone-modifying complexes	1	132.8×	0.030	KMT2D
Deactivation of the beta-catenin transactivating complex	1	116.5×	0.030	KMT2D
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	1	107.7×	0.030	KMT2D
Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	1	98.5×	0.030	KMT2D
PKMTs methylate histone lysines	1	80.4×	0.030	KMT2D
Epigenetic regulation by WDR5-containing histone modifying complexes	1	77.2×	0.030	KMT2D
CHD6, CHD7, CHD8, CHD9 subfamily	1	74.2×	0.030	CHD7
Transcriptional regulation by RUNX1	1	73.2×	0.030	KMT2D
Formation of the beta-catenin:TCF transactivating complex	1	60.1×	0.030	KMT2D
RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function	1	60.1×	0.030	KMT2D
TCF dependent signaling in response to WNT	1	58.9×	0.030	KMT2D
Signaling by WNT	1	56.0×	0.030	KMT2D
Activation of anterior HOX genes in hindbrain development during early embryogenesis	1	45.7×	0.034	KMT2D
MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis	1	41.4×	0.034	KMT2D
Chromatin organization	1	40.8×	0.034	KMT2D
Chromatin modifying enzymes	1	36.1×	0.035	KMT2D
Epigenetic regulation of gene expression	1	35.7×	0.035	KMT2D
RNA Polymerase II Transcription	1	11.3×	0.104	KMT2D
Gene expression (Transcription)	1	8.9×	0.125	KMT2D
Generic Transcription Pathway	1	7.5×	0.139	KMT2D
Developmental Biology	1	7.2×	0.139	KMT2D
Signal Transduction	1	5.1×	0.187	KMT2D

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
right ventricular compact myocardium morphogenesis	1	8426.0×	0.003	CHD7
beta-catenin-TCF complex assembly	1	8426.0×	0.003	KMT2D
cranial nerve development	1	2808.7×	0.004	CHD7
olfactory nerve development	1	2808.7×	0.004	CHD7
regulation of growth hormone secretion	1	2808.7×	0.004	CHD7
oocyte growth	1	2106.5×	0.004	KMT2D
chordate embryonic development	1	1404.3×	0.004	CHD7
female genitalia development	1	1203.7×	0.004	CHD7
nose development	1	1203.7×	0.004	CHD7
semicircular canal morphogenesis	1	1203.7×	0.004	CHD7
epithelium development	1	1053.2×	0.004	CHD7
olfactory behavior	1	936.2×	0.004	CHD7
regulation of DNA-templated transcription	2	31.6×	0.004	CHD7, KMT2D
genitalia development	1	842.6×	0.004	CHD7
atrioventricular canal development	1	766.0×	0.005	CHD7
adult heart development	1	601.9×	0.005	CHD7
positive regulation of intracellular estrogen receptor signaling pathway	1	601.9×	0.005	KMT2D
cardiac septum morphogenesis	1	601.9×	0.005	CHD7
secondary palate development	1	601.9×	0.005	CHD7
ventricular trabecula myocardium morphogenesis	1	526.6×	0.005	CHD7
aorta morphogenesis	1	443.5×	0.005	CHD7
innervation	1	443.5×	0.005	CHD7
face development	1	401.2×	0.006	CHD7
olfactory bulb development	1	383.0×	0.006	CHD7
regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	1	337.0×	0.006	CHD7
embryonic hindlimb morphogenesis	1	290.6×	0.007	CHD7
blood circulation	1	255.3×	0.007	CHD7
adult walking behavior	1	247.8×	0.007	CHD7
positive regulation of multicellular organism growth	1	247.8×	0.007	CHD7
limb development	1	205.5×	0.008	CHD7

Therapeutics

Drug target analysis

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

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
CHD7	0	0
KMT2D	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
KMT2D	11	Binding:11

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	CHD7, KMT2D

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)
CHD7	0	—
KMT2D	11	—

Clinical trials & evidence

Clinical trials

Clinical trials: 9.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	7
PHASE4	1
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03605537	PHASE4	WITHDRAWN	Use of Mometasone Eluting Stent in Choanal Atresia
NCT07052214	PHASE3	RECRUITING	PSMA PET Combined With MRI for the Detection of PCa
NCT04680130	Not specified	ENROLLING_BY_INVITATION	Clinico-Pathologic-Genetic-Imaging Study of Neurodegenerative and Related Disorders
NCT06820190	Not specified	RECRUITING	Analgesic Efficacy of Multiple Mid-Transverse Process to Pleura (MTP) Block and PCA in Idiopathic Scoliosis Patients Undergoing Posterior Spinal Fusion
NCT07051109	Not specified	RECRUITING	Dual-chamber Patient-controlled Analgesia for Postoperative Recovery
NCT07173023	Not specified	NOT_YET_RECRUITING	A Comparative Study of Endoscopic Choanal Canalization and Mitomycin C Application vs Endoscopic Crossover Flap Technique
NCT04929054	Not specified	UNKNOWN	PCR Based CEUS in BI RADS 4A Nodules
NCT05688371	Not specified	UNKNOWN	Dexmedetomidine Plus Low Dose Morphine Versus Standard Dose of Morphine in PCA in Children .
NCT05845281	Not specified	COMPLETED	Comparison of Erector Spinae Plane Block and Intravenous Patient-controlled Analgesia in Percutaneous Nephrolithotomy

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
GALLIUM GA 68 GOZETOTIDE	4	1
CHEMBL4589226	0	1