Anosmia

Summary

Anosmia (MONDO:0010528) is a disease with 3 cohort genes and 55 clinical trials. Top therapeutic interventions include theophylline anhydrous, dexamethasone, and diosmin.

At a glance

• Cohort genes: 3
• ClinVar variants: 3
• Clinical trials: 55

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	anosmia
Mondo ID	MONDO:0010528
MeSH	D000857
ICD-11	1599308422
SNOMED CT	44169009
UMLS	C0003126
MedGen	1950
Is cancer (heuristic)	no

Also known as: anosmia · anosmia (disease)

Data availability: 3 ClinVar variants · 2 GenCC gene-disease records · 1 HPO phenotype.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › otorhinolaryngologic disease › nasal disorder › anosmia

Related subtypes (4): paranasal sinus disorder, nasal cavity disorder, nasal cavity and paranasal sinus lethal midline granuloma, nasal dermoid cyst

Subtypes (2): isolated congenital anosmia, anosmia, isolated congenital, X-linked

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:

2 uncertain significance, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
375763	NM_015295.3(SMCHD1):c.1199A>T (p.Gln400Leu)	SMCHD1	Pathogenic	no assertion criteria provided
267805	46;XY;t(7;12)(q21.13;q24)dn		Uncertain significance	criteria provided, single submitter
375760	NM_015295.3(SMCHD1):c.1034A>G (p.Gln345Arg)	SMCHD1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 4 · 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
CNGA2	Supportive	Autosomal dominant	isolated congenital anosmia	2
TENM1	Supportive	Autosomal dominant	isolated congenital anosmia	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CNGA2	Orphanet:88620	Isolated congenital anosmia
TENM1	Orphanet:88620	Isolated congenital anosmia
SMCHD1	Orphanet:2250	Hyposmia-nasal and ocular hypoplasia-hypogonadotropic hypogonadism syndrome
SMCHD1	Orphanet:269	Facioscapulohumeral dystrophy

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
CNGA2	HGNC:2149	ENSG00000183862	Q16280	Cyclic nucleotide-gated channel alpha-2	gencc
TENM1	HGNC:8117	ENSG00000009694	Q9UKZ4	Teneurin-1	gencc
SMCHD1	HGNC:29090	ENSG00000101596	A6NHR9	Structural maintenance of chromosomes flexible hinge domain-containing protein 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CNGA2	Cyclic nucleotide-gated channel alpha-2	Pore-forming subunit of the olfactory cyclic nucleotide-gated channel.
TENM1	Teneurin-1	Involved in neural development, regulating the establishment of proper connectivity within the nervous system.
SMCHD1	Structural maintenance of chromosomes flexible hinge domain-containing protein 1	Non-canonical member of the structural maintenance of chromosomes (SMC) protein family that plays a key role in epigenetic silencing by regulating chromatin architecture.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · 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
Ion channel	1	37.2×	0.053
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CNGA2	Ion channel	yes		cNMP-bd_dom, Ion_trans_dom, RmlC-like_jellyroll
TENM1	Other/Unknown	no		EGF, YD, Ten_N
SMCHD1	Other/Unknown	no		SMC_hinge, SMC_hinge_sf, HATPase_C_sf

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)	1
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
colonic epithelium	2
cortical plate	1
ventricular zone	1
cerebellar vermis	1
endothelial cell	1
paraflocculus	1
blood	1
calcaneal tendon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CNGA2	2		yes	colonic epithelium, ventricular zone, cortical plate
TENM1	218	tissue_specific	marker	cerebellar vermis, paraflocculus, endothelial cell
SMCHD1	290	ubiquitous	marker	calcaneal tendon, colonic epithelium, blood

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SMCHD1	1,888
TENM1	1,691
CNGA2	1,047

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CNGA2	Q16280	2
SMCHD1	A6NHR9	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TENM1	Q9UKZ4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 3 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
VxPx cargo-targeting to cilium	1	519.1×	0.004	CNGA2
Olfactory Signaling Pathway	1	144.6×	0.007	CNGA2

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
nose development	1	802.5×	0.010	SMCHD1
autosome genomic imprinting	1	802.5×	0.010	SMCHD1
regulation of transcription by RNA polymerase III	1	561.7×	0.010	TENM1
dosage compensation by inactivation of X chromosome	1	510.7×	0.010	SMCHD1
sensory perception of chemical stimulus	1	374.5×	0.010	CNGA2
positive regulation of double-strand break repair via nonhomologous end joining	1	330.4×	0.010	SMCHD1
random inactivation of X chromosome	1	312.1×	0.010	SMCHD1
positive regulation of peptidyl-serine phosphorylation	1	255.3×	0.010	TENM1
positive regulation of intracellular protein transport	1	224.7×	0.010	TENM1
positive regulation of MAP kinase activity	1	216.1×	0.010	TENM1
monoatomic cation transmembrane transport	1	208.1×	0.010	CNGA2
negative regulation of double-strand break repair via homologous recombination	1	208.1×	0.010	SMCHD1
chromosome organization	1	193.7×	0.010	SMCHD1
positive regulation of filopodium assembly	1	187.2×	0.010	TENM1
positive regulation of DNA repair	1	119.5×	0.014	SMCHD1
positive regulation of actin filament polymerization	1	110.1×	0.015	TENM1
sodium ion transport	1	90.6×	0.017	CNGA2
neuron development	1	85.1×	0.017	TENM1
double-strand break repair	1	67.7×	0.020	SMCHD1
potassium ion transport	1	63.8×	0.020	CNGA2
calcium ion transport	1	60.4×	0.020	CNGA2
neuropeptide signaling pathway	1	57.3×	0.020	TENM1
sensory perception of smell	1	52.0×	0.022	CNGA2
immune response	1	15.7×	0.066	TENM1
nervous system development	1	15.3×	0.066	TENM1
negative regulation of cell population proliferation	1	14.0×	0.070	TENM1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SMCHD1	1	2
CNGA2	0	0
TENM1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	SMCHD1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SMCHD1	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	SMCHD1

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	SMCHD1
C	Druggable family + PDB, no drug	1	CNGA2
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	TENM1

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)
CNGA2	0	—
TENM1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 55.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	32
PHASE2	8
PHASE3	5
PHASE4	3
PHASE2/PHASE3	2
PHASE1/PHASE2	2
EARLY_PHASE1	2
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04528329	PHASE4	UNKNOWN	Anosmia and / or Ageusia and Early Corticosteroid Use
NCT04797936	PHASE4	COMPLETED	BNO 1030 Extract (Imupret) in the Treatment of Mild Forms of COVID-19
NCT04853836	PHASE4	COMPLETED	Olfactory Disfunction and Co-ultraPEALut
NCT07151703	PHASE3	NOT_YET_RECRUITING	Topical Versus Injection PRP for Olfactory Dysfunction
NCT03680911	PHASE3	TERMINATED	NAC for Head Trauma-induced Anosmia
NCT04361474	PHASE3	COMPLETED	Trial Evaluating the Efficacy of Local Budesonide Therapy in the Management of Hyposmia in COVID-19 Patients Without Signs of Severity
NCT04484493	PHASE3	COMPLETED	Corticosteroid Nasal Spray in COVID-19 Anosmia
NCT04951362	PHASE2/PHASE3	UNKNOWN	Role of Ivermectin Nanosuspension as Nasal Spray in Treatment of Persistant Post covid19 Anosmia
NCT05226546	PHASE2/PHASE3	COMPLETED	Effectiveness and Safety of Platelet Rich Plasma (PRP) on Persistent Olfactory Dysfunction Related to COVID-19
NCT05461365	PHASE3	COMPLETED	Intranasal Insulin for COVID-19-related Smell Loss
NCT06204432	PHASE2	ACTIVE_NOT_RECRUITING	Sodium Citrate in Smell Retraining for People With Post-COVID-19 Olfactory Dysfunction
NCT03990766	PHASE2	COMPLETED	Smell Changes & Efficacy of Nasal Theophylline
NCT04422275	PHASE2	WITHDRAWN	Coronavirus Smell Therapy for Anosmia Recovery
NCT04495816	PHASE2	COMPLETED	COVID-19 Anosmia Study
NCT04657809	PHASE2	COMPLETED	Clinical Assessment of Insulin Fast Dissolving Film in Treatment of Post Infection Anosmia
NCT04715932	PHASE2	COMPLETED	Study of Hesperidin Therapy on COVID-19 Symptoms (HESPERIDIN)
NCT04789499	PHASE2	COMPLETED	Smell in Covid-19 and Efficacy of Nasal Theophylline
NCT04964414	PHASE1/PHASE2	TERMINATED	Treatment of Pediatric Patients That Lost Sense of Smell Due to COVID-19
NCT05184192	PHASE2	COMPLETED	Efficacy of Gabapentin for Post-Covid-19 Olfactory Dysfunction
NCT05445921	PHASE1/PHASE2	COMPLETED	Stellate Ganglion Block for COVID-19-Induced Olfactory Dysfunction
NCT06498687	PHASE1	WITHDRAWN	Theophylline Nasal Spray for PD-Related Hyposmia and Anosmia
NCT02481609	EARLY_PHASE1	COMPLETED	NAC Trial for Anosmia
NCT05395845	EARLY_PHASE1	UNKNOWN	Value of Platelet-Rich Plasma in Post Severe Acute Respiratory Syndrome Coronavirus 2
NCT05040659	Not specified	ACTIVE_NOT_RECRUITING	Longitudinal At Home Smell Testing to Detect Infection by SARS-CoV-2
NCT05061329	Not specified	RECRUITING	The Nasal Microbiome and Its Importance in Disease
NCT05364125	Not specified	RECRUITING	Olfactory Training on Smell Dysfunction Patients in HK
NCT05384561	Not specified	RECRUITING	Olfactory Training As a Treatment for Olfactory Dysfunction Post COVID-19
NCT05562050	Not specified	ACTIVE_NOT_RECRUITING	Characteristics of the Anosmic Olfactory Mucosa
NCT05740683	Not specified	RECRUITING	Alpha-synuclein Rt-quic and Neurologic Symptoms in Persons With idiOpathic anosMiA
NCT06423495	Not specified	RECRUITING	Efficacy of Photobiomodulation in the Rehabilitation of Olfactory Dysfunctions Induced by Long COVID-19
NCT06600438	Not specified	NOT_YET_RECRUITING	Slow-SPEED UK: A Double-Blind Randomised Feasibility Trial
NCT06733636	Not specified	RECRUITING	Scents of Progress: Leveraging a Novel Device for Olfactory Training in Older Adults
NCT06766279	Not specified	RECRUITING	Investigating the Efficacy of OMT to Recover Olfactory Perception After COVID-19
NCT06930248	Not specified	NOT_YET_RECRUITING	Efficacy of Platelet-rich Plasma in Management of Anosmia
NCT07149428	Not specified	NOT_YET_RECRUITING	Longitudinal Deep Phenotyping of Central Mechanisms in Dysosmia: A Pilot Study Using Electrobulbogram (EBG), Functional MRI (fMRI), and Diffusion-Weighted Imaging (DWI)
NCT07383415	Not specified	NOT_YET_RECRUITING	Intranasal Platelet-Rich Plasma With or Without Topical Insulin for Post-Inflammatory Anosmia
NCT02179554	Not specified	WITHDRAWN	Does Cardiopulmonary Bypass Change Olfaction?
NCT04377815	Not specified	COMPLETED	Finding Out if COVID-19 Infection Can be pREdicted by ChAnges in Smell and/or Taste
NCT04384042	Not specified	UNKNOWN	Malaysian COVID-19 Anosmia Study (Phase 2) - A Nationwide Multicentre Case-Control Study
NCT04388618	Not specified	COMPLETED	Investigating Anosmia and Ageusia in COVID-19 Adult Patients in Saudi Arabia

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
THEOPHYLLINE ANHYDROUS	4	6
DEXAMETHASONE	4	1
DIOSMIN	4	1
SODIUM CITRATE	4	1
HESPERIDIN	3	1