CTNND1

Chr 11AD

catenin delta 1

Also known as: BCDS2, CAS, CTNND, P120CAS, P120CTN, p120, p120(CAS), p120(CTN)

NCBI Gene: 1500 ENSG00000198561 UniProt: O60716 OMIM: 601045

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]

OMIM Research

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Blepharocheilodontic syndrome 2MIM #617681

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · blepharocheilodontic syndrome 2 · AD · ClinGen 2024

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.18

LOEUF· LoF intol.

LOF

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.18LOEUF

pLI 1.000

Z-score 6.00

OE 0.08 (0.04–0.18)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.08Z-score

OE missense 0.76 (0.70–0.82)

432 obs / 571.7 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.08 (0.04–0.18)

0≤0.351.4

Missense OE?0.76 (0.70–0.82)

0≤0.61.4

Synonymous OE?0.80

0≤1.21.6

LoF obs/exp: 4 / 49.6Missense obs/exp: 432 / 571.7Syn Z: 2.19

Background carrier burden — how many people carry a rare variant somewhere in CTNND1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 40

1,111 rare PASS variants

Rare truncating (LoF)

1 in 2,800

69 rare PASS variants

Rare synonymous (reference)

1 in 110

454 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CTNND1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 46	1 in 2,800
South Asian	~43k	1 in 51	1 in 1,500
Remaining (unassigned)	~30k	1 in 43	1 in 3,600
European (Finnish)	~27k	1 in 110	≈ 1 in 6,200
Admixed American	~22k	1 in 49	1 in 1,900
African / African American	~21k	1 in 44	1 in 4,000
East Asian	~20k	1 in 64	1 in 680
Ashkenazi Jewish	~13k	1 in 270	≈ 1 in 11,000
Middle Eastern	~2,884	1 in 54	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.