CNN2

protein-coding

calponin 2

Gene summary

The protein encoded by this gene, which can bind actin, calmodulin, troponin C, and tropomyosin, may function in the structural organization of actin filaments. The encoded protein could play a role in smooth muscle contraction and cell adhesion. Several pseudogenes of this gene have been identified, and are present on chromosomes 1, 2, 3, 6, 9, 11, 13, 15, 16, 21 and 22. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2015]

MANE transcript

NM_004368.4

Inheritance

—

ClinVar variants

P:2U:55B:1

Top phenotype

Pulmonary artery atresia

gnomAD constraint

pLI —, LoF o/e 0.36

Max pathogenic AF

—

Genomic locus

chr19:1,026,586-1,039,068

External References & Databases

Ensembl (ENSG00000064666)

Transcript & Mutation Effects

hg38 • Region Span ~12.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CNN2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 50

Pulmonary artery atresiaTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004368.4. 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			1 clinvar			1
missense	2 clinvar		51 clinvar	1 clinvar		54
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	2	0	55	1	0	58

Highest pathogenic variant AF is 0.0027850568

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 59 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004368.4	RefSeq	NP_004359.1	7	MANE Select
ENST00000263097.9	Ensembl	ENSP00000263097.2	7	MANE Select
NM_001303499.2	RefSeq	NP_001290428.1	7	Standard
NM_001303501.2	RefSeq	NP_001290430.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Myometrial Relaxation and Contraction Pathways
Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation
Neutrophil degranulation
Innate Immune System
Immune System

Biological Process

cytoskeleton organization
actomyosin structure organization
regulation of actin filament-based process
interleukin-12-mediated signaling pathway
neutrophil degranulation

Molecular Function

actin binding
calmodulin binding
cadherin binding

Cellular Component

stress fiber
extracellular region
cytoskeleton
cell-cell junction
focal adhesion

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000263097
Coding exons: 7
Length: 12771
Individuals with no LoFs: 125717
Homozygous LoFs: 0
Heterozygous LoFs: 15
Defined: 125732
p: 0.0000597

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.152	210	204	1.03	0.0000130	2023
Missense (PolyPhen)		32	39.6	0.80808		512
Synonymous	-1.11	105	91.5	1.15	0.00000701	581
Loss of Function	2.19	5	13.8	0.363	6.86e-7	148

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0.000099	0.000098	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Thin filament-associated protein that is implicated in the regulation and modulation of smooth muscle contraction. It is capable of binding to actin, calmodulin, troponin C and tropomyosin. The interaction of calponin with actin inhibits the actomyosin Mg-ATPase activity.;

Recessive Scores

pRec: 0.145

Intolerance Scores

LoFtool: 0.224
RVIS EVS: -0.78
RVIS percentile EVS: 12.77

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.411

Gene Damage Prediction

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