Isolated congenital anosmia

Summary

Isolated congenital anosmia (MONDO:0007137) 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		15	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	isolated congenital anosmia
Mondo ID	MONDO:0007137
MeSH	C535983
OMIM	107200
Orphanet	88620
ICD-11	1603572540
SNOMED CT	230502003
UMLS	C0393778
MedGen	95992
GARD	0009486
Is cancer (heuristic)	no

Also known as: ANIC · anosmia, isolated congenital · congenital anosmia

Data availability: 2 GenCC gene-disease records.

Disease family

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

Related subtypes (1): 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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 2 · 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

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
CNGA2	HGNC:2149	ENSG00000183862	Q16280	Cyclic nucleotide-gated channel alpha-2	gencc
TENM1	HGNC:8117	ENSG00000009694	Q9UKZ4	Teneurin-1	gencc

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.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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	55.8×	0.036
Other/Unknown	1	0.9×	0.805

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

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

Top tissues across cohort

Tissue	Cohort genes
colonic epithelium	1
cortical plate	1
ventricular zone	1
cerebellar vermis	1
endothelial cell	1
paraflocculus	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

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TENM1	1,691
CNGA2	1,047

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CNGA2	Q16280	2

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 2 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 2 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 transcription by RNA polymerase III	1	842.6×	0.009	TENM1
sensory perception of chemical stimulus	1	561.7×	0.009	CNGA2
positive regulation of peptidyl-serine phosphorylation	1	383.0×	0.009	TENM1
positive regulation of intracellular protein transport	1	337.0×	0.009	TENM1
positive regulation of MAP kinase activity	1	324.1×	0.009	TENM1
monoatomic cation transmembrane transport	1	312.1×	0.009	CNGA2
positive regulation of filopodium assembly	1	280.9×	0.009	TENM1
positive regulation of actin filament polymerization	1	165.2×	0.013	TENM1
sodium ion transport	1	135.9×	0.013	CNGA2
neuron development	1	127.7×	0.013	TENM1
potassium ion transport	1	95.8×	0.015	CNGA2
calcium ion transport	1	90.6×	0.015	CNGA2
neuropeptide signaling pathway	1	86.0×	0.015	TENM1
sensory perception of smell	1	78.0×	0.016	CNGA2
immune response	1	23.5×	0.046	TENM1
nervous system development	1	23.0×	0.046	TENM1
negative regulation of cell population proliferation	1	21.1×	0.047	TENM1

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 2 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
CNGA2	0	0
TENM1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	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: 0.