CNGA2

protein-coding

cyclic nucleotide gated channel subunit alpha 2, the group of Cyclic nucleotide gated channels

Gene summary

The protein encoded by this gene represents the alpha subunit of a cyclic nucleotide-gated olfactory channel. The encoded protein contains a carboxy-terminal leucine zipper that mediates channel formation. [provided by RefSeq, Jan 2010]

Previous symbols:

CNCA1
CNCA

MANE transcript

NM_005140.3

Inheritance

XL, AD

ClinVar variants

U:71B:19

Top phenotype

isolated congenital anosmia

gnomAD constraint

pLI —, LoF o/e 0.44

Max pathogenic AF

—

Genomic locus

chrX:151,734,746-151,745,564

External References & Databases

Ensembl (ENSG00000183862)

Transcript & Mutation Effects

hg38 • Region Span ~10.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

anosmiaLIMITED

Inheritance Pattern: XL

Disease ID:MONDO:0010528

Submitter: Ambry Genetics

isolated congenital anosmiaSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007137

Submitter: Orphanet

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CNGA2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 72

not providedTotal: 20

Congenital portosystemic shuntTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005140.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				5 clinvar	3 clinvar	8
missense			70 clinvar	5 clinvar	6 clinvar	81
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	71	10	9	90

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005140.3	RefSeq	NP_005131.1	6	MANE Select
ENST00000329903.5	Ensembl	ENSP00000328478.4	6	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

cAMP signaling pathway - Homo sapiens (human)
Olfactory transduction - Homo sapiens (human)
NO-cGMP-PKG mediated Neuroprotection
VxPx cargo-targeting to cilium
Cargo trafficking to the periciliary membrane

Biological Process

sensory perception of smell
response to stimulus
cation transmembrane transport

Molecular Function

intracellular cAMP-activated cation channel activity
intracellular cGMP-activated cation channel activity
calmodulin binding
cAMP binding
cGMP binding

Cellular Component

Golgi membrane
integral component of membrane
Golgi-associated vesicle membrane
ciliary membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000329903
Coding exons: 6
Length: 6854
Individuals with no LoFs: 125720
Homozygous LoFs: 8
Heterozygous LoFs: 12
Defined: 125740
p: 0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0285	273	272	1.00	0.0000219	4365
Missense (PolyPhen)		111	118.43	0.9373		1953
Synonymous	-0.294	109	105	1.04	0.00000806	1308
Loss of Function	2.24	8	18.3	0.436	0.00000158	277

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000073	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000072	0.000054	rare
Finnish	0.000063	0.000046	rare
European (Non-Finnish)	0.00017	0.00012	rare
South Asian	0.00010	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Odorant signal transduction is probably mediated by a G- protein coupled cascade using cAMP as second messenger. The olfactory channel can be shown to be activated by cyclic nucleotides which leads to a depolarization of olfactory sensory neurons.;

Recessive Scores

pRec: 0.114

Intolerance Scores

LoFtool: 0.0646
RVIS EVS: 0.49
RVIS percentile EVS: 79.61

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.132

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium