AXIN2

axin 2

Basic information

Region (hg38): 17:65528562-65561648

Links

ENSG00000168646 ∙ NCBI:8313 ∙ OMIM:604025 ∙ HGNC:904 ∙ Uniprot:Q9Y2T1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• oligodontia-cancer predisposition syndrome (Definitive), mode of inheritance: AD
• tooth agenesis (Supportive), mode of inheritance: AD
• oligodontia-cancer predisposition syndrome (Supportive), mode of inheritance: AD
• craniosynostosis (Limited), mode of inheritance: AD
• oligodontia-cancer predisposition syndrome (Strong), mode of inheritance: AD
• oligodontia-cancer predisposition syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Oligodontia-colorectal cancer syndrome	AD	Oncologic	Although the condition may be clinically recognizable in many individuals, the oncologic risk may not be clear, and awareness may allow surveillance for and early treatment of related malignancies (eg, breast cancer, colorectal cancer), which may reduce morbidity and mortality	Dental; Oncologic	15042511; 21626677; 21416598
Some individuals appear to have dental anomalies without obviously increased colorectal cancer risk

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AXIN2 gene.

• Oligodontia-cancer predisposition syndrome (2704 variants)
• Hereditary cancer-predisposing syndrome (1764 variants)
• not provided (511 variants)
• not specified (263 variants)
• Colorectal cancer (182 variants)
• AXIN2-related condition (22 variants)
• Oligodontia-cancer predisposition syndrome;Colorectal cancer (14 variants)
• Ovarian cancer (9 variants)
• AXIN2-related attenuated familial adenomatous polyposis (7 variants)
• Inborn genetic diseases (7 variants)
• Oligodontia-cancer predisposition syndrome;Carcinoma of colon (6 variants)
• Carcinoma of colon;Oligodontia-cancer predisposition syndrome (4 variants)
• Oligodontia-cancer predisposition syndrome;AXIN2-related attenuated familial adenomatous polyposis (3 variants)
• Oligodontia;Colorectal cancer (2 variants)
• Colorectal cancer;Oligodontia-cancer predisposition syndrome (2 variants)
• Malignant tumor of breast (2 variants)
• AXIN2-related disorder (2 variants)
• Carcinoma of colon (1 variants)
• Colorectal carcinoma (1 variants)
• Colorectal cancer;Oligodontia (1 variants)
• Aganglionic megacolon (1 variants)
• AXIN2-related attenuated familial adenomatous polyposis;Oligodontia-cancer predisposition syndrome (1 variants)
• Craniosynostosis syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AXIN2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			11	754	6	771
missense			1717	10	2	1729
nonsense	34	8	9			51
start loss			6			6
frameshift	71	15	15			101
inframe indel			51		1	52
splice donor/acceptor (+/-2bp)		19	9			28
splice region		1	48	53		102
non coding			47	247	37	331
Total	105	42	1865	1011	46

Highest pathogenic variant AF is 0.00000658

Variants in AXIN2

This is a list of pathogenic ClinVar variants found in the AXIN2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-65528767-A-G		Oligodontia-cancer predisposition syndrome	Uncertain significance (Jan 13, 2018)
17-65528796-C-T		Oligodontia-cancer predisposition syndrome	Uncertain significance (Apr 27, 2017)
17-65528823-G-A		Oligodontia-cancer predisposition syndrome	Uncertain significance (Jan 12, 2018)
17-65528840-A-C		Oligodontia-cancer predisposition syndrome	Uncertain significance (Jan 12, 2018)
17-65528960-G-A		Oligodontia-cancer predisposition syndrome	Uncertain significance (Jan 13, 2018)
17-65528964-A-T		Oligodontia-cancer predisposition syndrome	Benign (Jan 13, 2018)
17-65528989-A-C		Oligodontia-cancer predisposition syndrome	Uncertain significance (Jan 13, 2018)
17-65529019-A-C		Oligodontia-cancer predisposition syndrome	Benign (Jan 13, 2018)
17-65529130-C-T		Oligodontia-cancer predisposition syndrome	Benign (Jan 13, 2018)
17-65529182-G-T		Oligodontia-cancer predisposition syndrome	Benign (Jan 12, 2018)
17-65529239-C-T		Oligodontia-cancer predisposition syndrome	Uncertain significance (Jan 13, 2018)
17-65529273-C-G		Oligodontia-cancer predisposition syndrome	Uncertain significance (Jan 12, 2018)
17-65529344-G-GA		Oligodontia-cancer predisposition syndrome	Uncertain significance (Jun 14, 2016)
17-65529415-A-G		Oligodontia-cancer predisposition syndrome	Uncertain significance (Jan 12, 2018)
17-65529476-A-C		Oligodontia-cancer predisposition syndrome	Benign (Jan 12, 2018)
17-65529487-G-A		Oligodontia-cancer predisposition syndrome	Uncertain significance (Apr 27, 2017)
17-65529488-CACTCCTAGCTCA-C			Likely benign (Feb 01, 2023)
17-65529507-A-G		Oligodontia-cancer predisposition syndrome	Conflicting classifications of pathogenicity (Aug 01, 2022)
17-65529576-G-C		Oligodontia-cancer predisposition syndrome	Uncertain significance (Jan 12, 2018)
17-65529600-T-C		Oligodontia-cancer predisposition syndrome	Uncertain significance (Jan 13, 2018)
17-65529631-A-G		Oligodontia-cancer predisposition syndrome	Uncertain significance (Jan 13, 2018)
17-65529650-T-C		Oligodontia-cancer predisposition syndrome	Benign (Jan 13, 2018)
17-65529656-T-G		Oligodontia-cancer predisposition syndrome	Uncertain significance (Jan 13, 2018)
17-65529667-G-T		Oligodontia-cancer predisposition syndrome	Benign (Jan 13, 2018)
17-65529683-T-A		Oligodontia-cancer predisposition syndrome	Uncertain significance (Apr 27, 2017)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AXIN2	protein_coding	protein_coding	ENST00000307078	10	33085

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.570	0.430	125733	0	15	125748	0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0665	506	510	0.992	0.0000333	5478
Missense in Polyphen		124	184.17	0.67329		2122
Synonymous	-1.93	263	226	1.16	0.0000167	1679
Loss of Function	4.21	7	33.2	0.211	0.00000181	394

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000116	0.000116
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000834	0.0000791
Middle Eastern	0.00	0.00
South Asian	0.0000659	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Inhibitor of the Wnt signaling pathway. Down-regulates beta-catenin. Probably facilitate the phosphorylation of beta- catenin and APC by GSK3B (By similarity). {ECO:0000250}.
• Disease: DISEASE: Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. {ECO:0000269|PubMed:11017067}. Note=The gene represented in this entry is involved in disease pathogenesis.; DISEASE: Oligodontia-colorectal cancer syndrome (ODCRCS) [MIM:608615]: Affected individuals manifest severe tooth agenesis and colorectal cancer or precancerous lesions of variable types. {ECO:0000269|PubMed:15042511}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Gastric cancer - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Breast cancer - Homo sapiens (human);Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human);Basal cell carcinoma - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Hippo signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Wnt signaling pathway - Homo sapiens (human);Endometrial cancer - Homo sapiens (human);Colorectal cancer - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);WNT-Core;Neural Crest Differentiation;Degradation of beta-catenin by the destruction complex;Mesodermal Commitment Pathway;TCF dependent signaling in response to WNT;Beta-catenin independent WNT signaling;Wnt Signaling Pathway;Wnt-beta-catenin Signaling Pathway in Leukemia;Wnt Signaling Pathway and Pluripotency;Endometrial cancer;Chromosomal and microsatellite instability in colorectal cancer;Degradation of beta-catenin by the destruction complex;Signaling by WNT;Signal Transduction;Repression of WNT target genes;Post-translational protein modification;Metabolism of proteins;Ca2+ pathway;Beta-catenin independent WNT signaling;Ub-specific processing proteases;Deubiquitination;Wnt Canonical;Regulation of nuclear beta catenin signaling and target gene transcription;Degradation of beta catenin;Validated nuclear estrogen receptor alpha network;Binding of TCF/LEF:CTNNB1 to target gene promoters;Formation of the beta-catenin:TCF transactivating complex;TCF dependent signaling in response to WNT;Wnt Mammals;Degradation of AXIN (Consensus)

Recessive Scores

• pRec: 0.289

Intolerance Scores

• loftool: 0.224
• rvis_EVS: 0.32
• rvis_percentile_EVS: 72.85

Haploinsufficiency Scores

• pHI: 0.325
• hipred: Y
• hipred_score: 0.793
• ghis: 0.467

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.994

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Axin2
• Phenotype: embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; reproductive system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; skeleton phenotype; cellular phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; craniofacial phenotype

Gene ontology

• Biological process: somitogenesis;positive regulation of protein phosphorylation;intramembranous ossification;secondary heart field specification;chondrocyte differentiation involved in endochondral bone morphogenesis;cell population proliferation;negative regulation of cell population proliferation;positive regulation of epithelial to mesenchymal transition;positive regulation of cell death;Wnt signaling pathway;bone mineralization;regulation of mismatch repair;cellular protein localization;odontogenesis;maintenance of DNA repeat elements;negative regulation of osteoblast differentiation;mRNA stabilization;regulation of chondrocyte development;regulation of centromeric sister chromatid cohesion;negative regulation of canonical Wnt signaling pathway;positive regulation of canonical Wnt signaling pathway;beta-catenin-TCF complex assembly
• Cellular component: nucleus;cytoplasm;centrosome;cytosol;beta-catenin destruction complex
• Molecular function: protein binding;beta-catenin binding;enzyme binding;ubiquitin protein ligase binding;I-SMAD binding