CTNNB1catenin beta 1

SFARI Gene Score

High Confidence Criteria 1.1

Autism Reports / Total Reports

13 / 43

Rare Variants / Common Variants

122 / 0

EAGLE Score

32.75

Strong Learn More

Aliases

CTNNB1, OK/SW-cl.35, CTNNB

Associated Syndromes

Chromosome Band

3p22.1

Associated Disorders

DD/NDD, ASD, EPS, ID

Genetic Category

Rare Single Gene Mutation, Syndromic

Relevance to Autism

Two de novo variants (one nonsense, one missense) in the CTNNB1 gene were identified in unrelated simplex ASD cases (PMIDs 22495309 and 23160955). Three de novo LoF variants in CTNNB1 (two frameshift, one nonsense) have been identified in unrelated patients with a similar phenotypic profile: severe ID, absent or very limited speech, microcephaly, and spasticity (PMIDs 23033978 and 24614104). De novo LoF variants in CTNNB1 were identified in a total of six patients from the Deciphering Developmental Disorders study (PMID 25533962). A de novo LoF variant in CTNNB1 was identifed in a proband from the Pediatric Cardiac Genetics Consortium who presented with ASD, developmental delay, and intellectual disability in addition to congenital heart disease (Homsy et al., 2015). Conditional knockout mice with CTNNB1-deficient parvalbumin interneurons exhibited significantly impaired object recognition and social interactions, elevated repetitive behaviors, and increased anxiety (Dong et al., 2016). Two de novo protein-truncating variants in CTNNB1 were identified in ASD probands from the Autism Sequencing Consortium in Satterstrom et al., 2020; two protein-truncating variants in this gene were also observed in case samples from the Danish iPSYCH study in the same report. TADA analysis of de novo variants from the Simons Simplex Collection and the Autism Sequencing Consortium and protein-truncating variants from iPSYCH in Satterstrom et al., 2020 identified CTNNB1 as a candidate gene with a false discovery rate (FDR) 0.01. A two-stage analysis of rare de novo and inherited coding variants in 42,607 ASD cases, including 35,130 new cases from the SPARK cohort, in Zhou et al., 2022 identified CTNNB1 as a gene reaching study-wide significance based on 5,754 constraint genes (P < 8.69E-06).

Molecular Function

The protein encoded by this gene is part of a complex of proteins that constitute adherens junctions (AJs). AJs are necessary for the creation and maintenance of epithelial cell layers by regulating cell growth and adhesion between cells. The encoded protein also anchors the actin cytoskeleton and may be responsible for transmitting the contact inhibition signal that causes cells to stop dividing once the epithelial sheet is complete. Finally, this protein binds to the product of the APC gene, which is mutated in adenomatous polyposis of the colon.

SFARI Genomic Platforms

GPF browser SFARI genome browser

Reports (43)
Variants (122)
Gene Score
Protein Interactions (63)

Reports related to CTNNB1 (43 Reports)

#	Type	Title	Author, Year	Autism Report	Associated Disorders
1	Primary	Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations	O'Roak BJ , et al. (2012)	Yes	-
2	Support	Diagnostic exome sequencing in persons with severe intellectual disability	de Ligt J , et al. (2012)	No	Epilepsy, ASD
3	Support	Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders	O'Roak BJ , et al. (2012)	Yes	-
4	Support	Dominant ?-catenin mutations cause intellectual disability with recognizable syndromic features	Tucci V , et al. (2014)	No	Autistic features
5	Support	A new intellectual disability syndrome caused by CTNNB1 haploinsufficiency	Dubruc E , et al. (2014)	No	-
6	Support	Large-scale discovery of novel genetic causes of developmental disorders	Deciphering Developmental Disorders Study (2014)	No	-
7	Recent Recommendation	Low load for disruptive mutations in autism genes and their biased transmission	Iossifov I , et al. (2015)	Yes	-
8	Recent Recommendation	De novo mutations in congenital heart disease with neurodevelopmental and other congenital anomalies	Homsy J , et al. (2016)	No	ASD, DD, ID
9	Support	Comprehensive molecular testing in patients with high functioning autism spectrum disorder	Alvarez-Mora MI , et al. (2016)	Yes	-
10	Support	A de novo CTNNB1 nonsense mutation associated with syndromic atypical hyperekplexia, microcephaly and intellectual disability: a case report	Winczewska-Wiktor A , et al. (2016)	No	-
11	Recent Recommendation	Deletion of CTNNB1 in inhibitory circuitry contributes to autism-associated behavioral defects	Dong F , et al. (2016)	No	-
12	Support	Altered proliferation and networks in neural cells derived from idiopathic autistic individuals	Marchetto MC , et al. (2016)	Yes	-
13	Support	Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability	Lelieveld SH et al. (2016)	No	-
14	Recent Recommendation	Hepatocyte Growth Factor Modulates MET Receptor Tyrosine Kinase and ?-Catenin Functional Interactions to Enhance Synapse Formation	Xie Z , et al. (2016)	No	-
15	Support	Clinical exome sequencing: results from 2819 samples reflecting 1000 families	Trujillano D , et al. (2016)	No	DD, ID, microcephaly
16	Support	Clinical features associated with CTNNB1 de novo loss of function mutations in ten individuals	Kharbanda M , et al. (2016)	No	Hypotonia, spasticity, microcephaly
17	Support	A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology	Vissers LE , et al. (2017)	No	-
18	Support	Exome sequencing identifies a de novo mutation of CTNNB1 gene in a patient mainly presented with retinal detachment, lens and vitreous opacities, microcephaly, and developmental delay: Case report and literature review	Li N , et al. (2017)	No	-
19	Support	Improved diagnostic yield compared with targeted gene sequencing panels suggests a role for whole-genome sequencing as a first-tier genetic test	Lionel AC , et al. (2017)	No	-
20	Support	Exonic Mosaic Mutations Contribute Risk for Autism Spectrum Disorder	Krupp DR , et al. (2017)	Yes	-
21	Support	Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population	Monies D , et al. (2019)	No	Autistic features
22	Support	Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism	Satterstrom FK et al. (2020)	Yes	-
23	Support	Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders	Wang T et al. (2020)	Yes	-
24	Support	-	Rossetti LZ et al. (2021)	No	ASD, stereotypy
25	Support	-	Kwong AK et al. (2021)	No	-
26	Support	-	Ho S et al. (2022)	No	-
27	Support	-	Pode-Shakked B et al. (2021)	No	-
28	Support	-	Taylor RL et al. (2022)	No	-
29	Support	-	Hu C et al. (2022)	Yes	-
30	Support	-	Lee S et al. (2022)	No	ID, autistic features
31	Support	-	Zhou X et al. (2022)	Yes	-
32	Support	-	Yuan B et al. (2023)	Yes	-
33	Support	-	Chaves LD et al. (2023)	No	-
34	Support	-	Wang J et al. (2023)	Yes	-
35	Support	-	Sinibaldi L et al. (2023)	No	Autistic features, ADHD
36	Support	-	Ji Y et al. (2023)	No	Stereotypy
37	Support	-	Roberta Onesimo et al. (2023)	No	ASD
38	Support	-	Nikoletta Nagy et al. (2024)	No	Stereotypy
39	Support	-	Khemika K Sudnawa et al. (2024)	No	ASD, stereotypy
40	Support	-	Marketa Wayhelova et al. (2024)	No	-
41	Support	-	Tamam Khalaf et al. (2024)	No	-
42	Support	-	Ruohao Wu et al. (2024)	Yes	-
43	Support	-	Axel Schmidt et al. (2024)	No	Autistic behavior

Rare Variants (122)

Allele Change	Residue Change	Variant Type	Inheritance Pattern	Parental Transmission	Family Type	PubMed ID	Author, Year
-	-	copy_number_loss	De novo	-	Simplex	24668549	Dubruc E , et al. (2014)
c.242-1G>C	-	splice_site_variant	Unknown	-	-	34558805	Ho S et al. (2022)
c.367C>T	p.Gln123Ter	stop_gained	Unknown	-	-	34558805	Ho S et al. (2022)
c.493C>T	p.Gln165Ter	stop_gained	Unknown	-	-	34558805	Ho S et al. (2022)
c.163G>T	p.Glu55Ter	stop_gained	De novo	-	-	35935366	Lee S et al. (2022)
c.1759C>T	p.Arg587Ter	stop_gained	Unknown	-	-	34558805	Ho S et al. (2022)
c.1082-1G>C	-	splice_site_variant	De novo	-	-	35935366	Lee S et al. (2022)
c.268C>T	p.Arg90Ter	stop_gained	Unknown	-	-	33004838	Wang T et al. (2020)
c.283C>T	p.Arg95Ter	stop_gained	Unknown	-	-	33004838	Wang T et al. (2020)
c.241+1G>A	-	splice_site_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.1148G>A	p.Trp383Ter	stop_gained	De novo	-	-	35935366	Lee S et al. (2022)
c.1420C>T	p.Arg474Ter	stop_gained	De novo	-	-	35935366	Lee S et al. (2022)
c.1543C>T	p.Arg515Ter	stop_gained	De novo	-	-	35935366	Lee S et al. (2022)
c.1759C>T	p.Arg587Ter	stop_gained	De novo	-	-	35935366	Lee S et al. (2022)
c.1867C>T	p.Gln623Ter	stop_gained	De novo	-	-	35935366	Lee S et al. (2022)
c.1081+1G>C	-	splice_site_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.82C>G	p.Gln28Glu	missense_variant	Unknown	-	-	35741772	Hu C et al. (2022)
c.1420C>T	p.Arg474Ter	stop_gained	Unknown	-	-	33004838	Wang T et al. (2020)
c.367C>T	p.Gln123Ter	stop_gained	De novo	-	-	33446253	Kwong AK et al. (2021)
c.2117C>A	p.Pro706His	missense_variant	Unknown	-	-	35741772	Hu C et al. (2022)
c.257dup	p.Tyr86Ter	stop_gained	De novo	-	Simplex	37560515	Ji Y et al. (2023)
c.1603C>T	p.Arg535Ter	stop_gained	De novo	-	-	36943625	Chaves LD et al. (2023)
c.1543C>T	p.Arg515Ter	stop_gained	De novo	-	-	23033978	de Ligt J , et al. (2012)
c.998dup	p.Tyr333Ter	stop_gained	De novo	-	-	37455656	Sinibaldi L et al. (2023)
c.999C>A	p.Tyr333Ter	stop_gained	De novo	-	-	37455656	Sinibaldi L et al. (2023)
c.999del	p.Tyr333Ter	stop_gained	De novo	-	-	37455656	Sinibaldi L et al. (2023)
c.1013G>C	p.Trp338Ser	missense_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.1457G>A	p.Arg486His	missense_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.1582C>T	p.Arg528Cys	missense_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.1693C>T	p.Arg565Cys	missense_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.2017C>T	p.Arg673Trp	missense_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.1613T>G	p.Leu538Arg	missense_variant	De novo	-	-	36881370	Yuan B et al. (2023)
c.1420C>T	p.Arg474Ter	stop_gained	De novo	-	-	28333917	Vissers LE , et al. (2017)
c.1962T>A	p.Tyr654Ter	stop_gained	De novo	-	-	33350591	Rossetti LZ et al. (2021)
c.1420C>T	p.Arg474Ter	stop_gained	De novo	-	-	37455656	Sinibaldi L et al. (2023)
c.1759C>T	p.Arg587Ter	stop_gained	De novo	-	-	37455656	Sinibaldi L et al. (2023)
c.2089G>T	p.Gly697Ter	stop_gained	Unknown	-	-	37455656	Sinibaldi L et al. (2023)
c.607C>T	p.Gln203Ter	stop_gained	De novo	-	-	27479843	Lelieveld SH et al. (2016)
c.999C>G	p.Tyr333Ter	stop_gained	De novo	-	-	27915094	Kharbanda M , et al. (2016)
c.226C>T	p.Gln76Ter	stop_gained	Unknown	-	-	27378147	Marchetto MC , et al. (2016)
c.1672C>T	p.Arg558Cys	stop_gained	De novo	-	Simplex	28514307	Li N , et al. (2017)
c.998dup	p.Tyr333Ter	frameshift_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.1420C>T	p.Arg474Ter	stop_gained	De novo	-	-	27479843	Lelieveld SH et al. (2016)
c.1420C>T	p.Arg474Ter	stop_gained	De novo	-	-	27915094	Kharbanda M , et al. (2016)
c.1603C>T	p.Arg535Ter	stop_gained	De novo	-	-	27915094	Kharbanda M , et al. (2016)
c.1612C>T	p.Gln538Ter	stop_gained	De novo	-	-	27915094	Kharbanda M , et al. (2016)
c.1801C>T	p.Gln601Ter	stop_gained	De novo	-	-	27915094	Kharbanda M , et al. (2016)
c.1759C>T	p.Arg587Ter	stop_gained	Unknown	-	-	38438125	Tamam Khalaf et al. (2024)
c.1543C>T	p.Arg515Ter	stop_gained	De novo	-	-	39039281	Axel Schmidt et al. (2024)
c.1900G>T	p.Glu634Ter	stop_gained	De novo	-	-	39039281	Axel Schmidt et al. (2024)
c.1723G>A	p.Gly575Arg	missense_variant	De novo	-	-	31130284	Monies D , et al. (2019)
c.976_979del	p.Asn326Ter	stop_gained	De novo	-	-	37455656	Sinibaldi L et al. (2023)
c.998dup	p.Tyr333Ter	stop_gained	Unknown	-	-	37895192	Roberta Onesimo et al. (2023)
c.337C>T	p.Gln113Ter	stop_gained	De novo	-	Simplex	38764027	Ruohao Wu et al. (2024)
c.1420C>T	p.Arg474Ter	stop_gained	Unknown	-	-	37895192	Roberta Onesimo et al. (2023)
c.1759C>T	p.Arg587Ter	stop_gained	Unknown	-	-	37895192	Roberta Onesimo et al. (2023)
c.1723G>A	p.Gly575Arg	missense_variant	De novo	-	-	33350591	Rossetti LZ et al. (2021)
c.596T>C	p.Val199Ala	missense_variant	Unknown	-	-	39039281	Axel Schmidt et al. (2024)
c.1186-18C>T	-	intron_variant	De novo	-	Simplex	31981491	Satterstrom FK et al. (2020)
c.1081+3_1083del	-	copy_number_loss	Unknown	-	-	37895192	Roberta Onesimo et al. (2023)
c.1849dup	p.Val617GlyfsTer4	frameshift_variant	Unknown	-	-	34558805	Ho S et al. (2022)
c.181del	p.Gln61LysfsTer19	frameshift_variant	De novo	-	-	35935366	Lee S et al. (2022)
c.1512G>A	p.Trp504Ter	stop_gained	De novo	-	Simplex	23160955	O'Roak BJ , et al. (2012)
c.1607T>G	p.Leu536Arg	missense_variant	De novo	-	Simplex	37393044	Wang J et al. (2023)
c.976_979del	p.Asn326Ter	stop_gained	Unknown	-	-	37895192	Roberta Onesimo et al. (2023)
c.1749dup	p.Val584CysfsTer25	frameshift_variant	De novo	-	-	35935366	Lee S et al. (2022)
c.429del	p.Asp144MetfsTer13	frameshift_variant	De novo	-	-	33004838	Wang T et al. (2020)
c.664del	p.Ser222ProfsTer20	frameshift_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.1981C>T	p.Gln661Ter	stop_gained	De novo	-	Simplex	27848944	Trujillano D , et al. (2016)
c.1685del	p.Glu562GlyfsTer8	frameshift_variant	De novo	-	-	26785492	Homsy J , et al. (2016)
c.1127G>A	p.Arg376His	missense_variant	De novo	-	Simplex	28867142	Krupp DR , et al. (2017)
c.925C>T	p.Gln309Ter	stop_gained	Unknown	Not maternal	-	23033978	de Ligt J , et al. (2012)
c.2255G>C	p.Gly752Ala	missense_variant	Unknown	-	-	26845707	Alvarez-Mora MI , et al. (2016)
c.863_864insG	p.Thr289AsnfsTer4	frameshift_variant	De novo	-	-	35935366	Lee S et al. (2022)
c.1652C>T	p.Thr551Met	missense_variant	De novo	-	Simplex	22495309	O'Roak BJ , et al. (2012)
c.1525-3C>G	-	splice_region_variant	De novo	-	Simplex	31981491	Satterstrom FK et al. (2020)
c.1105_1109del	p.His369AspfsTer24	frameshift_variant	Unknown	-	-	34558805	Ho S et al. (2022)
c.680dup	p.Leu229ThrfsTer5	frameshift_variant	De novo	-	-	37455656	Sinibaldi L et al. (2023)
c.811del	p.Met271TrpfsTer5	frameshift_variant	De novo	-	-	37455656	Sinibaldi L et al. (2023)
c.977del	p.Asn326IlefsTer2	frameshift_variant	De novo	-	-	37455656	Sinibaldi L et al. (2023)
c.1434_1435insC	p.Glu479ArgfsTer18	frameshift_variant	Unknown	-	-	34558805	Ho S et al. (2022)
c.1925_1926del	p.Glu642ValfsTer5	frameshift_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.2046_2047del	p.Phe683GlnfsTer9	frameshift_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.1740_1743del	p.Ala581GlyfsTer12	frameshift_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.1398_1399del	p.Ala467SerfsTer29	frameshift_variant	De novo	-	-	35982159	Zhou X et al. (2022)
c.1005del	p.Lys335AsnfsTer10	frameshift_variant	De novo	-	-	33350591	Rossetti LZ et al. (2021)
c.1665dup	p.Thr556AspfsTer16	frameshift_variant	De novo	-	-	33350591	Rossetti LZ et al. (2021)
c.1852del	p.Leu618SerfsTer23	frameshift_variant	De novo	-	-	37455656	Sinibaldi L et al. (2023)
c.1874del	p.Lys625ArgfsTer16	frameshift_variant	De novo	-	-	37455656	Sinibaldi L et al. (2023)
c.646G>A	p.Gly216Arg	missense_variant	De novo	-	Simplex	34580403	Pode-Shakked B et al. (2021)
c.232C>T	p.Gln78Ter	stop_gained	De novo	-	Simplex	26968164	Winczewska-Wiktor A , et al. (2016)
c.214_215del	p.Gln72ValfsTer9	frameshift_variant	De novo	-	-	33350591	Rossetti LZ et al. (2021)
c.1981C>A	p.Arg661=	synonymous_variant	De novo	-	Simplex	31981491	Satterstrom FK et al. (2020)
c.1586dup	p.Gln530AlafsTer42	frameshift_variant	De novo	-	Multiplex	37560515	Ji Y et al. (2023)
c.1287C>A	p.Cys429Ter	stop_gained	Unknown	-	Extended multiplex	31130284	Monies D , et al. (2019)
c.680dup	p.Leu229ThrfsTer5	frameshift_variant	Unknown	-	-	37895192	Roberta Onesimo et al. (2023)
c.977del	p.Asn326IlefsTer2	frameshift_variant	Unknown	-	-	37895192	Roberta Onesimo et al. (2023)
c.705dup	p.Gly236ArgfsTer35	frameshift_variant	De novo	-	Simplex	24614104	Tucci V , et al. (2014)
c.1064_1067del	p.Pro355LeufsTer3	frameshift_variant	De novo	-	-	28771251	Lionel AC , et al. (2017)
c.(1081+1_1082-1)_(2346+?)del	p.?	copy_number_loss	De novo	-	-	37455656	Sinibaldi L et al. (2023)
c.776_777del	p.Leu259ProfsTer11	frameshift_variant	De novo	-	-	33350591	Rossetti LZ et al. (2021)
c.677_678dup	p.Gly227ArgfsTer16	frameshift_variant	De novo	-	-	37455656	Sinibaldi L et al. (2023)
c.1272_1275del	p.Ser425ThrfsTer11	frameshift_variant	De novo	-	-	23033978	de Ligt J , et al. (2012)
c.1925_1926del	p.Glu642ValfsTer5	frameshift_variant	De novo	-	-	37455656	Sinibaldi L et al. (2023)
c.802_809del	p.Gly268AsnfsTer22	frameshift_variant	De novo	-	-	27915094	Kharbanda M , et al. (2016)
c.1874del	p.Lys625ArgfsTer16	frameshift_variant	Unknown	-	-	37895192	Roberta Onesimo et al. (2023)
Deletionof exons 8-15 of the CTNNB1 gene.	-	copy_number_loss	De novo	-	-	35935366	Lee S et al. (2022)
c.1925_1926del	p.Glu642ValfsTer5	frameshift_variant	De novo	-	Simplex	37393044	Wang J et al. (2023)
c.242-6T>G	-	splice_site_variant	De novo	-	-	25533962	Deciphering Developmental Disorders Study (2014)
c.2092_2096dup	p.Ile700LeufsTer37	frameshift_variant	Familial	Maternal	-	34558805	Ho S et al. (2022)
c.884C>G	p.Ala295Gly	missense_variant	Familial	Both parents	Simplex	35246174	Taylor RL et al. (2022)
c.1016_1025delinsT	p.Thr339_Arg342delinsIle	inframe_indel	De novo	-	-	33350591	Rossetti LZ et al. (2021)
c.1930del	p.Leu644PhefsTer35	frameshift_variant	De novo	-	Simplex	31981491	Satterstrom FK et al. (2020)
c.1904dup	p.Ala636SerfsTer12	frameshift_variant	De novo	-	Simplex	38225558	Nikoletta Nagy et al. (2024)
c.1925_1926del	p.Glu642GlyfsTer15	frameshift_variant	De novo	-	Simplex	27848944	Trujillano D , et al. (2016)
c.1043_1044del	p.Ser348CysfsTer4	frameshift_variant	De novo	-	Simplex	31981491	Satterstrom FK et al. (2020)
c.911dup	p.Leu304PhefsTer15	frameshift_variant	Familial	Paternal	-	38321498	Marketa Wayhelova et al. (2024)
c.1603C>T	p.Arg535Ter	stop_gained	De novo	-	Simplex	25533962	Deciphering Developmental Disorders Study (2014)
c.1981C>T	p.Arg661Ter	stop_gained	De novo	-	Simplex	25533962	Deciphering Developmental Disorders Study (2014)
c.998dup	p.Tyr333Ter	frameshift_variant	De novo	-	Simplex	25533962	Deciphering Developmental Disorders Study (2014)
c.1690del	p.Val564SerfsTer6	frameshift_variant	De novo	-	Simplex	25533962	Deciphering Developmental Disorders Study (2014)
c.1041_1044del	p.Val349AlafsTer9	frameshift_variant	De novo	-	Simplex	25533962	Deciphering Developmental Disorders Study (2014)

Common Variants

No common variants reported.

Current Score
Scoring History
3rd Party Scoring

SFARI Gene score

High Confidence

Score Delta: Score remained at 1

criteria met

See SFARI Gene'scoring criteria

High Confidence

See all Category 1 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

4/1/2021

Score remained at 1

Description

Reports Added

[Exome sequencing in paediatric patients with movement disorders2021]

1/1/2021

Score remained at 1

Description

Reports Added

[Missense variants in CTNNB1 can be associated with vitreoretinopathy-Seven new cases of CTNNB1-associated neurodevelopmental disorder including a previously unreported retinal phenotype2021]

10/1/2020

Score remained at 1

Description

Reports Added

[Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders2020]

1/1/2020

Score remained at 1

Description

Reports Added

[Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism2020]

10/1/2019

Decreased from 3 to 1

New Scoring Scheme

Description

Reports Added

[New Scoring Scheme]

7/1/2019

Decreased from 3 to 3

Description

Reports Added

[Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population.2019]

10/1/2017

Decreased from 3 to 3

Description

Reports Added

[Exonic Mosaic Mutations Contribute Risk for Autism Spectrum Disorder.2017]

7/1/2017

Decreased from 3 to 3

Description

Reports Added

[Improved diagnostic yield compared with targeted gene sequencing panels suggests a role for whole-genome sequencing as a first-tier genetic test.2017]

4/1/2017

Decreased from 3 to 3

Description

Reports Added

[Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.2012] [Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.2012] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Diagnostic exome sequencing in persons with severe intellectual disability.2012] [Dominant -catenin mutations cause intellectual disability with recognizable syndromic features.2014] [A new intellectual disability syndrome caused by CTNNB1 haploinsufficiency.2014] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [De novo mutations in congenital heart disease with neurodevelopmental and other congenital anomalies.2016] [Comprehensive molecular testing in patients with high functioning autism spectrum disorder.2016] [A de novo CTNNB1 nonsense mutation associated with syndromic atypical hyperekplexia, microcephaly and intellectual disability: a case report.2016] [Deletion of CTNNB1 in inhibitory circuitry contributes to autism-associated behavioral defects.2016] [Altered proliferation and networks in neural cells derived from idiopathic autistic individuals.2016] [Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability2016] [Hepatocyte Growth Factor Modulates MET Receptor Tyrosine Kinase and -Catenin Functional Interactions to Enhance Synapse Formation.2016] [Clinical exome sequencing: results from 2819 samples reflecting 1000 families.2016] [Clinical features associated with CTNNB1 de novo loss of function mutations in ten individuals.2016] [A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology.2017] [Exome sequencing identifies a de novo mutation of CTNNB1 gene in a patient mainly presented with retinal detachment, lens and vitreous opacities, m...2017]

1/1/2017

Decreased from 3 to 3

Description

Reports Added

[Clinical features associated with CTNNB1 de novo loss of function mutations in ten individuals.2016]

10/1/2016

Decreased from 3 to 3

Description

Reports Added

[Clinical exome sequencing: results from 2819 samples reflecting 1000 families.2016]

7/1/2016

Decreased from 3 to 3

Description

Two de novo LoF variants (one nonsense, one missense) identified in unrelated simplex ASD cases (PMIDs 22495309 and 23160955). Three de novo LoF variants in CTNNB1 (two frameshift, one nonsense) have been identified in unrelated patients with a similar phenotypic profile: severe ID, absent or very limited speech, microcephaly, and spasticity (PMIDs 23033978 and 24614104). De novo LoF variants in CTNNB1 were identified in a total of six patients from the Deciphering Developmental Disorders study (PMID 25533962). A de novo LoF variant in CTNNB1 was identifed in a proband from the Pediatric Cardiac Genetics Consortium who presented with ASD, developmental delay, and intellectual disability in addition to congenital heart disease (Homsy et al., 2015). Conditional knockout mice with CTNNB1-deficient parvalbumin interneurons exhibited significantly impaired object recognition and social interactions, elevated repetitive behaviors, and increased anxiety (Dong et al., 2016).

Reports Added

[Altered proliferation and networks in neural cells derived from idiopathic autistic individuals.2016] [Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability2016] [Hepatocyte Growth Factor Modulates MET Receptor Tyrosine Kinase and -Catenin Functional Interactions to Enhance Synapse Formation.2016]

4/1/2016

Decreased from 3 to 3

Description

Reports Added

1/1/2016

Decreased from 3 to 3

Description

Reports Added

1/1/2015

Decreased from 3 to 3

Description

Two de novo LGD variants (one nonsense, one missense) identified in unrelated simplex ASD cases (PMIDs 22495309 and 23160955). Three de novo LGD variants in CTNNB1 (two frameshift, one nonsense) have been identified in unrelated patients with a similar phenotypic profile: severe ID, absent or very limited speech, microcephaly, and spasticity (PMIDs 23033978 and 24614104).

Reports Added

[Large-scale discovery of novel genetic causes of developmental disorders.2014]

7/1/2014

No data

Increased from No data to 3

Description

4/1/2014

No data

Increased from No data to 3

Description

Reports Added

[A new intellectual disability syndrome caused by CTNNB1 haploinsufficiency.2014] [Diagnostic exome sequencing in persons with severe intellectual disability.2012] [Dominant -catenin mutations cause intellectual disability with recognizable syndromic features.2014]

Krishnan Probability Score

Score 0.49018309626028

Ranking 6229/25841 scored genes

[Show Scoring Methodology]

Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.

Original Source

ExAC Score

Score 0.99981274950371

Ranking 765/18225 scored genes

[Show Scoring Methodology]

The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt

Original Source

Iossifov Probability Score

Score 0.845

Ranking 199/239 scored genes

[Show Scoring Methodology]

Supplementary dataset S2 in the paper by Iossifov et al. (PNAS 112, E5600-E5607 (2015)) lists 239 genes with a probability of at least 0.8 of being associated with autism risk (column I). This probability metric combines the evidence from de novo likely-gene- disrupting and missense mutations and assesses it against the background mutation rate in unaffected individuals from the University of Washingtonâs Exome Variant Sequence database (evs.gs.washington.edu/EVS/). The list of probability scores can be found here: www.pnas.org/lookup/suppl/doi:10.1073/pnas.1516376112/- /DCSupplemental/pnas.1516376112.sd02.xlsx

Original Source

Sanders TADA Score

Score 0.4809139690573

Ranking 409/18665 scored genes

[Show Scoring Methodology]

The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).

Original Source

Larsen Cumulative Evidence Score

Score 14

Ranking 137/461 scored genes

[Show Scoring Methodology]

Larsen and colleagues generated gene scores based on the sum of evidence for all available ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size, and variant frequency in the general population. The approach was first presented in Mol Autism 7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from that paper.

Original Source

Zhang D Score

Score 0.30610409108621

Ranking 2646/20870 scored genes

[Show Scoring Methodology]

The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.

Original Source

External PIN Data

BioGRID Human Protein Reference Database

Interaction Table

Interactor Symbol	Interactor Name	Interactor Organism	Interactor Type	Entrez ID	Uniprot ID
AJAP1	Adherens junction-associated protein 1	Human	Protein Binding	55966	Q9UKB5
AKT1	v-akt murine thymoma viral oncogene homolog 1	Human	Protein Binding	207	P31749
AMOT	angiomotin	Human	Protein Binding	154796	Q4VCS5
APC2	adenomatosis polyposis coli 2	Human	RNA Binding	10297	O95996
BCL3	B-cell CLL/lymphoma 3	Human	Protein Binding	602	P20749
Bcl9l	B-cell CLL/lymphoma 9-like	Mouse	Protein Binding	80288	Q67FY2
BOC	BOC cell adhesion associated, oncogene regulated	Human	Protein Binding	91653	Q96DN7
C6ORF26	Suppressor APC domain-containing protein 1	Human	Protein Binding	401251	Q5SSQ6-2
CA9	Carbonic anhydrase 9	Human	Protein Binding	768	Q16790
CALCOCO1	calcium binding and coiled-coil domain 2	Chicken	Protein Binding	419993	E1BRX6
CBL	Cas-Br-M (murine) ecotropic retroviral transforming sequence	Human	Protein Modification	867	P22681
CCNA1	Cyclin-A1	Human	Protein Binding	8900	P78396
CCNE1	cyclin E1	Human	Protein Binding	898	P24864
CDH11	Cadherin-11	Human	Protein Binding	1009	P55287
cdh3-b	Beta-catenin-interacting protein 1	Human	Protein Binding	594865	Q9NSA3
CDH8	cadherin 8, type 2	Human	Protein Binding	1006	P55286
CDON	cell adhesion associated, oncogene regulated	Human	Protein Binding	50937	Q4KMG0
COPS3	COP9 constitutive photomorphogenic homolog subunit 3 (Arabidopsis)	Human	Protein Binding	8533	Q9UNS2
CSNK1D	casein kinase 1, delta	Rat	Protein Modification	64462	Q06486
DDB1	damage-specific DNA binding protein 1, 127kDa	Human	Protein Binding	1642	Q16531
DDX1	DEAD (Asp-Glu-Ala-Asp) box helicase 1	Human	Protein Binding	1653	A3RJH1
ERBB2	v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian)	Human	Protein Binding	2064	P04626
FANCL	Fanconi anemia, complementation group L	Human	Protein Modification	55120	Q9NW38
FOXO4	forkhead box O4	Human	Protein Binding	4303	P98177
GLIS2	Zinc finger protein GLIS2	Human	Protein Binding	84662	Q9BZE0
GRIK2	glutamate receptor, ionotropic, kainate 2	Rat	Protein Binding	54257	P42260
HDAC6	histone deacetylase 6	Human	Protein Modification	10013	Q9UBN7
HERC5	HECT and RLD domain containing E3 ubiquitin protein ligase 5	Human	Protein Binding	51191	B4DXV3
HINT1	histidine triad nucleotide binding protein 1	Human	Protein Binding	3094	P49773
HTT	Huntingtin	Human	Protein Binding	3064	P42858
ISG15	ISG15 ubiquitin-like modifier	Human	Protein Binding	9636	P05161
ITGA3	integrin, alpha 3 (antigen CD49C, alpha 3 subunit of VLA-3 receptor)	Human	Protein Binding	3675	P26006
KAT2A	K(lysine) acetyltransferase 2A	Human	Protein Binding	2648	Q92830
LATS2	LATS, large tumor suppressor, homolog 2 (Drosophila)	Human	Protein Binding	26524	Q9NRM7
LDHB	lactate dehydrogenase B	Human	Protein Binding	3945	P07195
MAGI2	membrane associated guanylate kinase, WW and PDZ domain containing 2	Human	Protein Binding	9863	Q86UL8
MAPK8	mitogen-activated protein kinase 8	Human	Protein Modification	5599	P45983
MAPK9	mitogen-activated protein kinase 9	Human	Protein Modification	5601	P45984
MEN1	multiple endocrine neoplasia I	Human	Protein Binding	4221	O00255
MICAL-L2	MICAL-like protein 2	Human	Direct Regulation	79778	Q8IY33
NONO	non-POU domain containing, octamer-binding	Human	Protein Binding	4841	Q15233
NUP62	nucleoporin 62kDa	Human	Protein Binding	23636	P37198
Pax6	paired box gene 6	Mouse	Direct Regulation	18508	P63015
PCDH9	protocadherin 9	Human	DNA Binding	5101	Q9HC56
PIN1	peptidylprolyl cis/trans isomerase, NIMA-interacting 1	Human	Protein Binding	5300	Q13526
PITX2	paired-like homeodomain 2	Human	Protein Binding	5308	Q99697
PML	promyelocytic leukemia	Human	Protein Binding	5371	P29590
PROP1	Homeobox protein prophet of Pit-1	Human	Protein Binding	5626	O75360
PRPF6	PRP6 pre-mRNA processing factor 6 homolog (S. cerevisiae)	Human	Protein Binding	24148	O94906
PTGS2	Prostaglandin G/H synthase 2	Human	RNA Binding	5743	P35354
PTPN1	protein tyrosine phosphatase, non-receptor type 1	Human	Protein Binding	5770	P18031
PTPRU	protein tyrosine phosphatase, receptor type, U	Human	Protein Binding	10076	Q92729
RB1CC1	RB1-inducible coiled-coil 1	Human	Protein Binding	9821	Q8TDY2
RBMX	RNA binding motif protein, X-linked	Human	Protein Binding	27316	P38159
RPLP2	ribosomal protein, large, P2	Human	Protein Binding	6181	P05387
RXRA	retinoid X receptor, alpha	Human	Protein Binding	6256	F1D8Q5
SATB1	SATB homeobox 1	Human	Protein Binding	6304	Q01826
SLAMF7	SLAM family member 7	Human	Protein Binding	57823	Q9NQ25-3
SUV39H1	suppressor of variegation 3-9 homolog 1 (Drosophila)	Human	Protein Binding	6839	O43463
TAX1BP3	Tax1-binding protein 3	Mouse	Protein Binding	30851	Q9DBG9
TIP60	Histone acetyltransferase KAT5	Human	Protein Binding	10524	Q92993
UHRF2	ubiquitin-like with PHD and ring finger domains 2, E3 ubiquitin protein ligase	Human	Protein Binding	115426	Q96PU4
VCL	vinculin	Human	Protein Binding	7414	B3KXA2

Human Gene Module / Chromosome 3 / CTNNB1

CTNNB1catenin beta 1

SFARI Gene Score

Autism Reports / Total Reports

Rare Variants / Common Variants

EAGLE Score

Aliases

Associated Syndromes

Chromosome Band

Associated Disorders

Genetic Category

Relevance to Autism

Molecular Function

External Links

Human

Mouse

SFARI Genomic Platforms

Reports related to CTNNB1 (43 Reports)

Rare Variants (122)

Common Variants

SFARI Gene score

High Confidence

Score Delta: Score remained at 1

criteria met

High Confidence

4/1/2021

Score remained at 1

Description

Reports Added

1/1/2021

Score remained at 1

Description

Reports Added

10/1/2020

Score remained at 1

Description

Reports Added

1/1/2020

Score remained at 1

Description

Reports Added

10/1/2019

Decreased from 3 to 1

New Scoring Scheme

Description

Reports Added

7/1/2019

Decreased from 3 to 3

Description

Reports Added

10/1/2017

Decreased from 3 to 3

Description

Reports Added

7/1/2017

Decreased from 3 to 3

Description

Reports Added

4/1/2017

Decreased from 3 to 3

Description

Reports Added

1/1/2017

Decreased from 3 to 3

Description

Reports Added

10/1/2016

Decreased from 3 to 3

Description

Reports Added

7/1/2016

Decreased from 3 to 3

Description

Reports Added

4/1/2016

Decreased from 3 to 3

Description

Reports Added

1/1/2016

Decreased from 3 to 3