AXIN1

axin 1, the group of Protein phosphatase 1 regulatory subunits

Basic information

Region (hg38): 16:287439-352723

Links

ENSG00000103126 ∙ NCBI:8312 ∙ OMIM:603816 ∙ HGNC:903 ∙ Uniprot:O15169 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• colorectal adenoma (Limited), mode of inheritance: AD
• caudal duplication (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Craniometadiaphyseal osteosclerosis with hip dysplasia	AR	Allergy/Immunology/Infectious; Cardiovascular	Individuals may have pancytopenia and susceptibility to infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial;Among other features, the condition may include cardiovascular anomalies, and awareness may allow early identification and management	Allergy/Immunology/Infectious; Cardiovascular; Gastrointestinal; Genitourinary; Hematologic; Musculoskeletal; Neurologic	12376942; 16773576; 37582359

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AXIN1 gene.

• Inborn genetic diseases (27 variants)
• not provided (21 variants)
• not specified (3 variants)
• Hepatocellular carcinoma;Caudal duplication (1 variants)
• Caudal duplication;Hepatocellular carcinoma (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AXIN1 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				6	7	13
missense			26	5	2	33
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				3		3
non coding						0
Total	0	0	26	11	9

Variants in AXIN1

This is a list of pathogenic ClinVar variants found in the AXIN1 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-288128-C-T			Likely benign (Mar 28, 2018)
16-288146-G-A			Benign (Jan 15, 2018)
16-288151-T-G		not specified	Uncertain significance (Aug 10, 2021)
16-288174-A-G		not specified	Uncertain significance (Jan 22, 2024)
16-288181-C-T		not specified	Uncertain significance (Oct 26, 2022)
16-288182-G-C		not specified	Uncertain significance (Mar 07, 2024)
16-288189-C-T		Caudal duplication;Hepatocellular carcinoma	Benign/Likely benign (Oct 18, 2021)
16-288190-G-A		Craniometadiaphyseal osteosclerosis with hip dysplasia	Pathogenic (Oct 26, 2023)
16-288207-A-AC		Craniometadiaphyseal osteosclerosis with hip dysplasia	Pathogenic (Oct 26, 2023)
16-288226-C-A		not specified	Uncertain significance (Dec 26, 2023)
16-288227-G-A		AXIN1-related disorder	Likely benign (Feb 19, 2019)
16-288232-C-T		not specified	Uncertain significance (Jan 20, 2023)
16-288257-C-T		AXIN1-related disorder	Likely benign (Jan 03, 2020)
16-289445-G-C		not specified	Uncertain significance (Sep 14, 2023)
16-289493-G-A		not specified	Benign (Nov 30, 2021)
16-289499-C-T		Caudal duplication;Hepatocellular carcinoma • AXIN1-related disorder	Benign/Likely benign (Dec 29, 2021)
16-289507-G-C		not specified	Uncertain significance (Sep 22, 2022)
16-289532-G-A		not specified	Likely benign (Jul 29, 2022)
16-289551-A-G		not specified	Uncertain significance (Oct 25, 2023)
16-291182-G-A		AXIN1-related disorder	Benign (Oct 07, 2019)
16-291218-C-T		not specified	Uncertain significance (Jan 10, 2022)
16-291261-G-A			Likely benign (Sep 25, 2018)
16-293480-G-A			Likely benign (May 21, 2018)
16-293481-G-A			Benign/Likely benign (Apr 01, 2022)
16-293484-G-A			Likely benign (Feb 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AXIN1	protein_coding	protein_coding	ENST00000262320	10	65234

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.408	0.592	125732	0	8	125740	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.01	481	548	0.878	0.0000382	5552
Missense in Polyphen		145	201.7	0.71888		2079
Synonymous	-2.24	289	244	1.18	0.0000195	1745
Loss of Function	4.31	8	35.8	0.223	0.00000215	385

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000290	0.0000290
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000390	0.0000352
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000658	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the beta-catenin destruction complex required for regulating CTNNB1 levels through phosphorylation and ubiquitination, and modulating Wnt-signaling (PubMed:12192039, PubMed:27098453). Controls dorsoventral patterning via two opposing effects; down-regulates CTNNB1 to inhibit the Wnt signaling pathway and ventralize embryos, but also dorsalizes embryos by activating a Wnt-independent JNK signaling pathway (PubMed:12192039). In Wnt signaling, probably facilitates the phosphorylation of CTNNB1 and APC by GSK3B (PubMed:12192039). Likely to function as a tumor suppressor. Enhances TGF-beta signaling by recruiting the RNF111 E3 ubiquitin ligase and promoting the degradation of inhibitory SMAD7 (PubMed:16601693). Also component of the AXIN1-HIPK2-TP53 complex which controls cell growth, apoptosis and development (PubMed:17210684). Facilitates the phosphorylation of TP53 by HIPK2 upon ultraviolet irradiation (PubMed:17210684). {ECO:0000269|PubMed:12192039, ECO:0000269|PubMed:16601693, ECO:0000269|PubMed:17210684, ECO:0000269|PubMed:27098453}.
• Disease: DISEASE: Hepatocellular carcinoma (HCC) [MIM:114550]: A primary malignant neoplasm of epithelial liver cells. The major risk factors for HCC are chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, prolonged dietary aflatoxin exposure, alcoholic cirrhosis, and cirrhosis due to other causes. {ECO:0000269|PubMed:12101426}. Note=The gene represented in this entry is involved in disease pathogenesis.; DISEASE: Caudal duplication anomaly (CADUA) [MIM:607864]: A condition characterized by the occurrence of duplications of different organs in the caudal region. {ECO:0000269|PubMed:16773576}. Note=The disease is caused by mutations affecting the gene represented in this entry. Caudal duplication anomaly is associated with hypermethylation of the AXIN1 promoter.
• 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;TGF-Ncore;TGF-Core;EGF-Ncore;Neural Crest Differentiation;Degradation of beta-catenin by the destruction complex;Mesodermal Commitment Pathway;Apoptosis-related network due to altered Notch3 in ovarian cancer;Extracellular vesicle-mediated signaling in recipient cells;Wnt Signaling Pathway;TGF-beta Signaling Pathway;Regulation of Wnt-B-catenin Signaling by Small Molecule Compounds;Association Between Physico-Chemical Features and Toxicity Associated Pathways;ESC Pluripotency Pathways;Wnt Signaling Pathway and Pluripotency;Transcriptional regulation by RUNX1;Endometrial cancer;Chromosomal and microsatellite instability in colorectal cancer;Wnt Signaling Pathway;DNA Damage Response (only ATM dependent);Degradation of beta-catenin by the destruction complex;Signaling by WNT;Signal Transduction;Gene expression (Transcription);wnt signaling pathway;segmentation clock;multi-step regulation of transcription by pitx2;Generic Transcription Pathway;Post-translational protein modification;Metabolism of proteins;RNA Polymerase II Transcription;inactivation of gsk3 by akt causes accumulation of b-catenin in alveolar macrophages;Disassembly of the destruction complex and recruitment of AXIN to the membrane;Ub-specific processing proteases;Deubiquitination;Signaling by Nuclear Receptors;Beta-catenin phosphorylation cascade;C-MYC pathway;Estrogen-dependent gene expression;Wnt;RUNX1 regulates estrogen receptor mediated transcription;RUNX1 regulates transcription of genes involved in WNT signaling;ESR-mediated signaling;Wnt Canonical;Degradation of beta catenin;Transcriptional regulation by RUNX1;N-cadherin signaling events;TCF dependent signaling in response to WNT;Canonical Wnt signaling pathway;Wnt Mammals;Presenilin action in Notch and Wnt signaling;TGF-beta receptor signaling;Degradation of AXIN (Consensus)

Recessive Scores

• pRec: 0.0978

Intolerance Scores

• loftool: 0.169
• rvis_EVS: -1.43
• rvis_percentile_EVS: 4.02

Haploinsufficiency Scores

• pHI: 0.286
• hipred: Y
• hipred_score: 0.756
• ghis: 0.534

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.996

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Axin1
• Phenotype: reproductive system phenotype; normal 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); 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); respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; skeleton phenotype; renal/urinary system phenotype; limbs/digits/tail 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); hearing/vestibular/ear phenotype; digestive/alimentary phenotype; growth/size/body region phenotype; cellular phenotype; craniofacial phenotype

Zebrafish Information Network

• Gene name: axin1
• Affected structure: intestinal epithelial cell
• Phenotype tag: abnormal
• Phenotype quality: proliferative

Gene ontology

• Biological process: positive regulation of protein phosphorylation;apoptotic process;multicellular organism development;positive regulation of peptidyl-threonine phosphorylation;Wnt signaling pathway;regulation of Wnt signaling pathway;positive regulation of protein ubiquitination;activation of protein kinase activity;positive regulation of peptidyl-serine phosphorylation;regulation of intracellular estrogen receptor signaling pathway;cellular protein-containing complex assembly;positive regulation of protein catabolic process;positive regulation of transcription, DNA-templated;positive regulation of JNK cascade;positive regulation of ubiquitin-protein transferase activity;negative regulation of canonical Wnt signaling pathway;positive regulation of canonical Wnt signaling pathway;beta-catenin destruction complex assembly;beta-catenin destruction complex disassembly;positive regulation of ubiquitin-dependent protein catabolic process
• Cellular component: nucleus;cytoplasm;cytosol;lateral plasma membrane;beta-catenin destruction complex;cytoplasmic vesicle;perinuclear region of cytoplasm;cell periphery
• Molecular function: protein binding;beta-catenin binding;enzyme binding;protein kinase binding;receptor signaling complex scaffold activity;ubiquitin protein ligase binding;protein-containing complex scaffold activity;signaling adaptor activity;identical protein binding;protein homodimerization activity;SMAD binding;armadillo repeat domain binding;I-SMAD binding