CTNNA2

protein-coding

catenin alpha 2, the group of Alpha catenins

Gene summary

Enables actin filament binding activity. Involved in negative regulation of Arp2/3 complex-mediated actin nucleation; regulation of neuron migration; and regulation of neuron projection development. Located in cytoplasm. Implicated in complex cortical dysplasia with other brain malformations 9. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001282597.3

Inheritance

ClinVar variants

P:9U:83B:31

Top phenotype

Cortical dysplasia, complex, with other brain malformations, 9

gnomAD constraint

pLI —, LoF o/e 0.22

Max pathogenic AF

—

Genomic locus

chr2:79,185,231-80,648,861

External References & Databases

Ensembl (ENSG00000066032)

Transcript & Mutation Effects

hg38 • Region Span ~1,463.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

cortical dysplasia, complex, with other brain malformations 9MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0032578

Submitter: Ambry Genetics

cortical dysplasia, complex, with other brain malformations 9STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032578

Submitter: Labcorp Genetics (formerly Invitae)

cortical dysplasia, complex, with other brain malformations 9STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032578

Submitter: G2P

Clinical Genomic Database (CGD)

Cortical dysplasia, complex, with other brain malformations, 9AR

Manifestation: Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 30013181

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CTNNA2 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 63

Inborn genetic diseasesTotal: 58

not providedTotal: 53

CTNNA2-related disorderTotal: 23

Cortical dysplasia, complex, with other brain malformations 9Total: 13

Hereditary breast ovarian cancer syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001282597.3. 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			1 clinvar	25 clinvar	4 clinvar	30
missense			78 clinvar	1 clinvar	1 clinvar	80
nonsense	3 clinvar	1 clinvar	2 clinvar			6
start loss						0
frameshift	1 clinvar	3 clinvar	1 clinvar			5
splice donor/acceptor (+/-2bp)	1 clinvar		1 clinvar			2
Total	5	4	83	26	5	123

Highest pathogenic variant AF is 0.0000065731524

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 36 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001282597.3	RefSeq	NP_001269526.1	18	MANE Select
ENST00000402739.9	Ensembl	ENSP00000384638.4	18	MANE Select
NM_001164883.2	RefSeq	NP_001158355.1	16	Standard
NM_001282598.2	RefSeq	NP_001269527.1	18	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Gastric cancer - Homo sapiens (human)
Adherens junction - Homo sapiens (human)
Arrhythmogenic right ventricular cardiomyopathy (ARVC) - Homo sapiens (human)
Hippo signaling pathway - Homo sapiens (human)
Bacterial invasion of epithelial cells - Homo sapiens (human)

Biological Process

cytoskeleton organization
axonogenesis
radial glia guided migration of Purkinje cell
dendrite morphogenesis
brain morphogenesis

Molecular Function

structural constituent of cytoskeleton
protein binding
identical protein binding
cadherin binding
actin filament binding

Cellular Component

nucleus
cytoplasm
cytosol
adherens junction
cell-cell adherens junction

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000466387
Coding exons: 17
Length: 1463549
Individuals with no LoFs: 125264
Homozygous LoFs: 0
Heterozygous LoFs: 21
Defined: 125285
p: 0.0000838

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.63	306	544	0.562	0.0000329	5931
Missense (PolyPhen)		72	158.38	0.45461		1732
Synonymous	-0.223	221	217	1.02	0.0000144	1775
Loss of Function	4.82	10	44.8	0.223	0.00000263	496

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00013	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000062	0.000062	rare
South Asian	0.00029	0.00029	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May function as a linker between cadherin adhesion receptors and the cytoskeleton to regulate cell-cell adhesion and differentiation in the nervous system. Regulates morphological plasticity of synapses and cerebellar and hippocampal lamination during development. Functions in the control of startle modulation. {ECO:0000250|UniProtKB:Q61301}.;

Recessive Scores

pRec: 0.113

Intolerance Scores

LoFtool: 0.502
RVIS EVS: -0.64
RVIS percentile EVS: 16.63

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.275

Gene Damage Prediction

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