Conductive hearing loss disorder

Summary

Conductive hearing loss disorder (MONDO:0020679) is a disease with 3 cohort genes and 32 clinical trials. Top therapeutic interventions include montelukast.

At a glance

• Cohort genes: 3
• ClinVar variants: 5
• Clinical trials: 32

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	conductive hearing loss disorder
Mondo ID	MONDO:0020679
NCIT	C27645
SNOMED CT	44057004
UMLS	C0018777
MedGen	9163
Is cancer (heuristic)	no

Also known as: conductive deafness · conductive hearing loss

Data availability: 5 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › auditory system disorder › hearing disorder › hearing loss disorder › conductive hearing loss disorder

Related subtypes (10): Johanson-Blizzard syndrome, noise induced hearing loss, nonsyndromic genetic hearing loss, sudden hearing loss disorder, sensorineural hearing loss disorder, central hearing loss, X-linked deafness, auditory neuropathy, hearing loss, mixed conductive-sensorineural, drug-induced hearing loss

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

5 retrieved; paginated sample, class counts are floors:

2 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity, 1 uncertain significance, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
267839	46;XY;inv(6)(q22.2q27)dn		Pathogenic	criteria provided, single submitter
279678	NM_013275.6(ANKRD11):c.1903_1907del (p.Lys635fs)	ANKRD11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
11755	NM_001110556.2(FLNA):c.620C>T (p.Pro207Leu)	FLNA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
228536	NM_080680.3(COL11A2):c.4559G>A (p.Arg1520His)	COL11A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
267835	46;XX;der(6)t(6;13)(q23.3;q22)inv(6)(p21.3q15);der(13)t(6;13)dn		Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 18 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ANKRD11	Orphanet:2332	KBG syndrome
ANKRD11	Orphanet:261250	16q24.3 microdeletion syndrome
COL11A2	Orphanet:1427	Autosomal recessive otospondylomegaepiphyseal dysplasia
COL11A2	Orphanet:166100	Autosomal dominant otospondylomegaepiphyseal dysplasia
COL11A2	Orphanet:2021	Fibrochondrogenesis
COL11A2	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
COL11A2	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
FLNA	Orphanet:1826	Frontometaphyseal dysplasia
FLNA	Orphanet:2301	Congenital short bowel syndrome
FLNA	Orphanet:2484	Melnick-Needles syndrome
FLNA	Orphanet:482606	X-linked keloid scarring-reduced joint mobility-increased optic cup-to-disc ratio syndrome
FLNA	Orphanet:555877	FLNA-related X-linked myxomatous valvular dysplasia
FLNA	Orphanet:75497	X-linked Ehlers-Danlos syndrome
FLNA	Orphanet:88630	Terminal osseous dysplasia-pigmentary defects syndrome
FLNA	Orphanet:90650	Otopalatodigital syndrome type 1
FLNA	Orphanet:90652	Otopalatodigital syndrome type 2
FLNA	Orphanet:98892	Periventricular nodular heterotopia
FLNA	Orphanet:99811	Neuronal intestinal pseudoobstruction

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ANKRD11	HGNC:21316	ENSG00000167522	Q6UB99	Ankyrin repeat domain-containing protein 11	clinvar
COL11A2	HGNC:2187	ENSG00000204248	P13942	Collagen alpha-2(XI) chain	clinvar
FLNA	HGNC:3754	ENSG00000196924	P21333	Filamin-A	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ANKRD11	Ankyrin repeat domain-containing protein 11	Chromatin regulator which modulates histone acetylation and gene expression in neural precursor cells.
COL11A2	Collagen alpha-2(XI) chain	May play an important role in fibrillogenesis by controlling lateral growth of collagen II fibrils.
FLNA	Filamin-A	Promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 1 · Druggable fraction: 0.33

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
Antibody/Immunoglobulin	1	9.7×	0.246
Scaffold/PPI	1	5.8×	0.246
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ANKRD11	Scaffold/PPI	no		Ankyrin_rpt, Ankyrin_rpt-contain_sf, ANKRD11
COL11A2	Other/Unknown	no		Fib_collagen_C, Laminin_G, Collagen
FLNA	Antibody/Immunoglobulin	yes		Filamin/ABP280_rpt, Actinin_actin-bd_CS, CH_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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
stromal cell of endometrium	1
sural nerve	1
tendon of biceps brachii	1
adenohypophysis	1
male germ line stem cell (sensu Vertebrata) in testis	1
pituitary gland	1
popliteal artery	1
right coronary artery	1
tibial artery	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ANKRD11	278	ubiquitous	marker	tendon of biceps brachii, sural nerve, stromal cell of endometrium
COL11A2	134	broad	yes	pituitary gland, male germ line stem cell (sensu Vertebrata) in testis, adenohypophysis
FLNA	285	ubiquitous	marker	right coronary artery, popliteal artery, tibial artery

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FLNA	5,321
ANKRD11	2,384
COL11A2	1,583

Structural data

PDB: 1 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FLNA	P21333	26

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
COL11A2	P13942	50.18
ANKRD11	Q6UB99	39.44

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 12. Enrichment computed across 3 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
OAS antiviral response	1	634.4×	0.011	FLNA
GP1b-IX-V activation signalling	1	475.8×	0.011	FLNA
Cell-extracellular matrix interactions	1	335.9×	0.011	FLNA
RHO GTPases activate PAKs	1	271.9×	0.011	FLNA
MET activates PTK2 signaling	1	190.3×	0.013	COL11A2
Collagen chain trimerization	1	129.8×	0.014	COL11A2
Developmental Lineage of Pancreatic Ductal Cells	1	114.2×	0.014	COL11A2
Assembly of collagen fibrils and other multimeric structures	1	100.2×	0.014	COL11A2
Collagen degradation	1	87.8×	0.014	COL11A2
Collagen biosynthesis and modifying enzymes	1	85.2×	0.014	COL11A2
Non-integrin membrane-ECM interactions	1	77.2×	0.014	COL11A2
Platelet degranulation	1	43.9×	0.023	FLNA

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of membrane repolarization during atrial cardiac muscle cell action potential	1	5617.3×	0.004	FLNA
regulation of membrane repolarization during cardiac muscle cell action potential	1	5617.3×	0.004	FLNA
tubulin deacetylation	1	1872.4×	0.006	FLNA
formation of radial glial scaffolds	1	1404.3×	0.006	FLNA
adenylate cyclase-inhibiting dopamine receptor signaling pathway	1	1123.5×	0.006	FLNA
soft palate development	1	1123.5×	0.006	COL11A2
establishment of Sertoli cell barrier	1	1123.5×	0.006	FLNA
protein localization to bicellular tight junction	1	936.2×	0.006	FLNA
negative regulation of transcription by RNA polymerase I	1	802.5×	0.007	FLNA
blood coagulation, intrinsic pathway	1	702.2×	0.007	FLNA
positive regulation of platelet activation	1	432.1×	0.008	FLNA
positive regulation of integrin-mediated signaling pathway	1	432.1×	0.008	FLNA
positive regulation of actin filament bundle assembly	1	401.2×	0.008	FLNA
actin crosslink formation	1	401.2×	0.008	FLNA
wound healing, spreading of cells	1	374.5×	0.008	FLNA
positive regulation of potassium ion transmembrane transport	1	330.4×	0.008	FLNA
positive regulation of neuron migration	1	330.4×	0.008	FLNA
positive regulation of neural precursor cell proliferation	1	255.3×	0.010	FLNA
obsolete negative regulation of DNA-binding transcription factor activity	1	244.2×	0.010	FLNA
megakaryocyte development	1	234.1×	0.010	FLNA
receptor clustering	1	208.1×	0.011	FLNA
protein localization to cell surface	1	165.2×	0.012	FLNA
skeletal system morphogenesis	1	165.2×	0.012	ANKRD11
face morphogenesis	1	165.2×	0.012	ANKRD11
establishment of protein localization	1	144.0×	0.013	FLNA
positive regulation of protein import into nucleus	1	140.4×	0.013	FLNA
semaphorin-plexin signaling pathway	1	133.8×	0.013	FLNA
positive regulation of substrate adhesion-dependent cell spreading	1	124.8×	0.013	FLNA
negative regulation of protein catabolic process	1	122.1×	0.013	FLNA
release of sequestered calcium ion into cytosol	1	114.6×	0.013	FLNA

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 3 evidence-associated genes (67%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FLNA	1	2
ANKRD11	0	0
COL11A2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	FLNA

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
FLNA	7	Binding:7

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	FLNA

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	FLNA
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	ANKRD11, COL11A2

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)
ANKRD11	0	—
COL11A2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 32.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	30
PHASE4	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00393159	PHASE4	UNKNOWN	The Influence of The Ear Popper on Serous Otitis Media and on the Accompanying Conductive Hearing Loss in Children
NCT01264510	PHASE4	WITHDRAWN	Evaluation of the Effectiveness of Bone-anchored Hearing Aids (Baha)
NCT07222202	Not specified	RECRUITING	Evaluation of Flexible Conductive Hearing Aids
NCT07557771	Not specified	RECRUITING	Wideband Tympanometry as a Non-behavioral Test of the Speech-weighted Middle Ear Transfer Function.
NCT07580287	Not specified	NOT_YET_RECRUITING	Comparative Study of Non-surgical Hearing Devices Based on Bone Conduction
NCT01445977	Not specified	UNKNOWN	SoundBite Hearing System Long Term Multi Site Patient Use Study
NCT01671176	Not specified	COMPLETED	Wide Diameter Bone Anchored Implant Study
NCT01807559	Not specified	UNKNOWN	SoundBite Hearing System 24 Month Multi Site Patient Use Study
NCT01967498	Not specified	UNKNOWN	Montelukast for Children With Chronic Otitis Media With Effusion (COME): A Double-blind, Placebo-controlled Study
NCT02064478	Not specified	COMPLETED	Clinical Survey of Oticon Medical Ponto Implants and a Surgical Technique With Tissue Preservation
NCT02092610	Not specified	COMPLETED	Long Term Stability, Survival and Tolerability of a (Novel) Baha® Implant System
NCT02274129	Not specified	COMPLETED	Clinical Survey of Oticon Medical Healing Cap
NCT02304692	Not specified	COMPLETED	Clinical Survey of Different Abutment Topologies
NCT02438618	Not specified	COMPLETED	Minimally Invasive Surgery for Ponto Bone Anchored Hearing Implants
NCT03086135	Not specified	COMPLETED	Clinical Performance of a New Implant System for Bone Conduction Hearing
NCT03143257	Not specified	COMPLETED	Ambispective Clinical Evaluation of Sophono™
NCT03271970	Not specified	WITHDRAWN	The Anatomic Determinants of Perforation Induced Hearing Loss
NCT03327194	Not specified	UNKNOWN	Use of ADHEAR, a Non-Implantable Bone Conduction Hearing System, in Children With Single Sided Deafness and/or Conductive Hearing Loss
NCT03374787	Not specified	COMPLETED	Evaluation of Sound Processor for a Transcutaneous System
NCT03541967	Not specified	WITHDRAWN	Comparison of a New Bone Conduction Hearing System to a Osteo-integrated Bone Conduction Hearing Aid on a Softband
NCT03723161	Not specified	COMPLETED	Evaluation of the Ponto Bone Anchored Hearing System in a Pediatric Atresia Population
NCT03746548	Not specified	COMPLETED	Audiological Benefit and Quality of Life With Two Bone Conduction Systems: ADHEAR vs. Contact Mini
NCT03848910	Not specified	COMPLETED	Subject´s Preference Regarding Hearing Performance and Functionality Using a New Sound Processor
NCT03864731	Not specified	COMPLETED	Quality of Life With Bone Conduction Hearing Device
NCT03916029	Not specified	COMPLETED	Hearing for Learning Initiative - a Health Facilitator Model for Otitis Media
NCT04320407	Not specified	COMPLETED	Osia CPT Code Study
NCT04803279	Not specified	COMPLETED	Investigating Hearing With Ponto 3 SuperPower, a Bone Anchored Hearing Aid - Investigating Hear
NCT05000931	Not specified	COMPLETED	Osia 2 Pediatric Expansion Study
NCT05628285	Not specified	COMPLETED	Evaluation of a Hearing Device for Transmitting Sound to the Inner Ear
NCT06164184	Not specified	UNKNOWN	Interest of the Cone Beam Scanner of Temporal Bones in the Analysis of Conductive Hearing Loss
NCT06535282	Not specified	COMPLETED	Brain Mechanism and Outcome of Surgical Intervention of Conductive Hearing Loss.
NCT07149480	Not specified	COMPLETED	Comparison of Postoperative Outcomes of Interlay vs Underlay Graft in Tympanoplasty

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
MONTELUKAST	4	1