CTNND1

protein-coding

catenin delta 1, the group of p120 catenin family|Armadillo repeat containing

Gene summary

This gene encodes a member of the Armadillo protein family, which function in adhesion between cells and signal transduction. Multiple translation initiation codons and alternative splicing result in many different isoforms being translated. Not all of the full-length natures of the described transcript variants have been determined. Read-through transcription also exists between this gene and the neighboring upstream thioredoxin-related transmembrane protein 2 (TMX2) gene. [provided by RefSeq, Dec 2010]

Previous symbols:

CTNND

MANE transcript

NM_001085458.2

Inheritance

ClinVar variants

P:45U:204B:37

Top phenotype

Blepharocheilodontic syndrome 2

gnomAD constraint

pLI —, LoF o/e 0.08

Max pathogenic AF

—

Genomic locus

chr11:57,753,243-57,819,546

External References & Databases

Ensembl (ENSG00000198561)

Transcript & Mutation Effects

hg38 • Region Span ~66.3 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

blepharocheilodontic syndrome 2STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0040503

Submitter: G2P

blepharocheilodontic syndromeSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007339

Submitter: Orphanet

blepharocheilodontic syndrome 2DEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0040503

Submitter: Ambry Genetics

blepharocheilodontic syndrome 2DEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0040503

Submitter: ClinGen

*CTNND1* was first reported in relation to autosomal dominant blepharocheilodontic syndrome (BCDS) in 2017 (Ghoumid et al.; PMID: 28301459). The phenotype of this disorder includes eye abnormalities, cleft lip/palate, and dental problems. 10 variants (frameshift, nonsense, missense) that have been reported in at least 15 probands in 3 publications (PMIDs: 28301459, 29348693, 32196547) are included in this curation. The maximum score for genetic evidence (12 pts.) has been reached. The mechanism of pathogenicity appears to be haploinsufficiency. This gene-disease relationship is also supported by experimental evidence (expression-level evidence, animal models; PMID: 32196547). Expression-level evidence in human embryos shows high and specific craniofacial expression. A mouse model and a xenopus model both recapitulate the human phenotype of craniofacial structural anomalies/abnormal expression in mutants. In summary, there is definitive evidence supporting the relationship between *CTNND1* and autosomal dominant BCDS. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Craniofacial Malformations GCEP on the meeting date 3/21/2024 (SOP Version 10).

blepharocheilodontic syndrome 2STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0040503

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Blepharocheilodontic syndrome 2AD

Manifestation: Craniofacial; Dermatologic; Dental

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: 28301459

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CTNND1 variants in ClinVar

7 Conditions Cataloged

Inborn genetic diseasesTotal: 130

not providedTotal: 106

CTNND1-related disorderTotal: 39

Blepharocheilodontic syndrome 2Total: 31

not specifiedTotal: 19

Cleft lip with or without cleft palateTotal: 11

Leber congenital amaurosis 2Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001085458.2. 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	15 clinvar	2 clinvar	18
missense	1 clinvar	3 clinvar	195 clinvar	16 clinvar	4 clinvar	219
nonsense	9 clinvar	10 clinvar	2 clinvar			21
start loss						0
frameshift	8 clinvar	8 clinvar	2 clinvar			18
splice donor/acceptor (+/-2bp)	3 clinvar	3 clinvar	4 clinvar			10
Total	21	24	204	31	6	286

Highest pathogenic variant AF is 0.0000013684253

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 168 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001085458.2	RefSeq	NP_001078927.1	19	MANE Select
ENST00000399050.10	Ensembl	ENSP00000382004.5	19	MANE Select
NM_001085459.2	RefSeq	NP_001078928.1	18	Standard
NM_001085460.2	RefSeq	NP_001078929.1	17	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
ctnnd1	Danio rerio	Structure: post-vent region Quality: decreased length abnormal

Gene / Model

Organism

Observed Phenotype

ctnnd1

Danio rerio

Structure: post-vent region

Quality: decreased length

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Adherens junction - Homo sapiens (human)
Rap1 signaling pathway - Homo sapiens (human)
Leukocyte transendothelial migration - Homo sapiens (human)
VEGFA-VEGFR2 Signaling Pathway
Wnt Signaling Pathway and Pluripotency

Biological Process

cell-cell junction assembly
cell adhesion
brain development
Wnt signaling pathway
adherens junction organization

Molecular Function

signaling receptor binding
protein binding
protein kinase binding
cadherin binding

Cellular Component

nucleus
cytoplasm
cytosol
plasma membrane
cell-cell junction

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000399050
Coding exons: 19
Length: 66304
Individuals with no LoFs: 124648
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 124656
p: 0.0000321

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.08	432	572	0.756	0.0000352	6260
Missense (PolyPhen)		141	215.27	0.65498		2269
Synonymous	2.19	160	199	0.803	0.0000105	1913
Loss of Function	6.00	4	49.6	0.0806	0.00000277	588

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000057	0.000056	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000045	0.000044	rare
South Asian	0.000035	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Binds to and inhibits the transcriptional repressor ZBTB33, which may lead to activation of target genes of the Wnt signaling pathway (By similarity). Associates with and regulates the cell adhesion properties of both C-, E- and N-cadherins, being critical for their surface stability. Implicated both in cell transformation by SRC and in ligand-induced receptor signaling through the EGF, PDGF, CSF-1 and ERBB2 receptors. Promotes GLIS2 C-terminal cleavage. {ECO:0000250, ECO:0000269|PubMed:17344476, ECO:0000269|PubMed:20371349}.;
Disease: DISEASE: Blepharocheilodontic syndrome 2 (BCDS2) [MIM:617681]: A form of blepharocheilodontic syndrome, a rare autosomal dominant disorder. It is characterized by lower eyelid ectropion, upper eyelid distichiasis, euryblepharon, bilateral cleft lip and palate, and features of ectodermal dysplasia, including hair anomalies, conical teeth and tooth agenesis. An additional rare manifestation is imperforate anus. There is considerable phenotypic variability among affected individuals. {ECO:0000269|PubMed:28301459}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.272

Intolerance Scores

LoFtool: 0.538
RVIS EVS: -0.73
RVIS percentile EVS: 14.2

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.664

Gene Damage Prediction

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