AXIN1 (axin 1)

Gene

• Entrez ID: 8312
• Gene name: Axin 1
• Gene symbol: AXIN1
• Synonyms (NCBI Gene): AXIN, CMDOH, PPP1R49
• Chromosome: 16
• Chromosome location: 16p13.3
• Summary: This gene encodes a cytoplasmic protein which contains a regulation of G-protein signaling (RGS) domain and a dishevelled and axin (DIX) domain. The encoded protein interacts with adenomatosis polyposis coli, catenin beta-1, glycogen synthase kinase 3 bet

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs587776627	GGGAATGTGAGGTAGGGGCACCCGCCCATTGA>-	Pathogenic	Frameshift variant, intron variant, non coding transcript variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT018487	hsa-miR-335-5p	Microarray	18185580
MIRT049195	hsa-miR-92a-3p	CLASH	23622248
MIRT044503	hsa-miR-320a	CLASH	23622248
MIRT041736	hsa-miR-484	CLASH	23622248
MIRT039102	hsa-miR-769-3p	CLASH	23622248
MIRT036160	hsa-miR-320c	CLASH	23622248
MIRT441132	hsa-miR-218-5p	HITS-CLIP	23212916
MIRT441132	hsa-miR-218-5p	HITS-CLIP	23212916
MIRT812373	hsa-miR-3613-3p	CLIP-seq
MIRT812374	hsa-miR-3691-3p	CLIP-seq
MIRT812375	hsa-miR-4251	CLIP-seq
MIRT812376	hsa-miR-4293	CLIP-seq
MIRT812377	hsa-miR-4324	CLIP-seq
MIRT812378	hsa-miR-4328	CLIP-seq
MIRT812379	hsa-miR-4528	CLIP-seq
MIRT812380	hsa-miR-4699-3p	CLIP-seq
MIRT812381	hsa-miR-4795-3p	CLIP-seq
MIRT812382	hsa-miR-539	CLIP-seq
MIRT812383	hsa-miR-596	CLIP-seq
MIRT812384	hsa-miR-602	CLIP-seq
MIRT812385	hsa-miR-657	CLIP-seq
MIRT1940251	hsa-miR-31	CLIP-seq
MIRT1940252	hsa-miR-4742-5p	CLIP-seq
MIRT1940253	hsa-miR-653	CLIP-seq
MIRT812377	hsa-miR-4324	CLIP-seq
MIRT1940254	hsa-miR-4736	CLIP-seq
MIRT2179166	hsa-miR-1200	CLIP-seq
MIRT2179167	hsa-miR-1321	CLIP-seq
MIRT2179168	hsa-miR-1911	CLIP-seq
MIRT2179169	hsa-miR-2355-5p	CLIP-seq
MIRT2179170	hsa-miR-3689d	CLIP-seq
MIRT812374	hsa-miR-3691-3p	CLIP-seq
MIRT2179171	hsa-miR-3944-3p	CLIP-seq
MIRT812377	hsa-miR-4324	CLIP-seq
MIRT1940254	hsa-miR-4736	CLIP-seq
MIRT2179172	hsa-miR-4739	CLIP-seq
MIRT2179173	hsa-miR-4756-5p	CLIP-seq
MIRT2179174	hsa-miR-544b	CLIP-seq
MIRT2444523	hsa-miR-1205	CLIP-seq
MIRT2444524	hsa-miR-1291	CLIP-seq
MIRT2444525	hsa-miR-3173-5p	CLIP-seq
MIRT2444526	hsa-miR-4650-5p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000209	Process	Protein polyubiquitination	IEA
GO:0001701	Process	In utero embryonic development	IEA
GO:0002039	Function	P53 binding	IEA
GO:0005515	Function	Protein binding	IPI	9601641, 10481074, 10644691, 10811618, 11738041, 12192039, 16169070, 16293619, 16601693, 17318175, 17318191, 17510365, 17588722, 17601533, 18786926, 19131971, 19166851, 19202075, 19249679, 19303846, 19390532, 19759537, 20080667, 21057547, 21087614, 21242974, 21245303, 21988832, 2215
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IDA	12072559, 21383061
GO:0005634	Component	Nucleus	IEA
GO:0005730	Component	Nucleolus	IDA
GO:0005737	Component	Cytoplasm	IDA	12072559, 17569865, 21383061
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	IBA
GO:0005886	Component	Plasma membrane	IEA
GO:0005938	Component	Cell cortex	IEA
GO:0006913	Process	Nucleocytoplasmic transport	IEA
GO:0006915	Process	Apoptotic process	IEA
GO:0007605	Process	Sensory perception of sound	IEA
GO:0008013	Function	Beta-catenin binding	IBA
GO:0008013	Function	Beta-catenin binding	IDA	10644691
GO:0008013	Function	Beta-catenin binding	IEA
GO:0008013	Function	Beta-catenin binding	IPI	21087614
GO:0009950	Process	Dorsal/ventral axis specification	IEA
GO:0009953	Process	Dorsal/ventral pattern formation	IEA
GO:0010629	Process	Negative regulation of gene expression	IEA
GO:0015630	Component	Microtubule cytoskeleton	IEA
GO:0016020	Component	Membrane	IEA
GO:0016055	Process	Wnt signaling pathway	IEA
GO:0016055	Process	Wnt signaling pathway	IEA
GO:0016328	Component	Lateral plasma membrane	IDA	12072559
GO:0019899	Function	Enzyme binding	IPI	19759537, 21383061, 21478859
GO:0019901	Function	Protein kinase binding	IBA
GO:0019901	Function	Protein kinase binding	IEA
GO:0019901	Function	Protein kinase binding	ISS
GO:0019904	Function	Protein domain specific binding	IEA
GO:0030163	Process	Protein catabolic process	IEA
GO:0030178	Process	Negative regulation of Wnt signaling pathway	IEA
GO:0030178	Process	Negative regulation of Wnt signaling pathway	IEA
GO:0030511	Process	Positive regulation of transforming growth factor beta receptor signaling pathway	IEA
GO:0030877	Component	Beta-catenin destruction complex	IBA
GO:0030877	Component	Beta-catenin destruction complex	IDA	9601641, 16188939, 18593713, 19759537
GO:0030877	Component	Beta-catenin destruction complex	IEA
GO:0030877	Component	Beta-catenin destruction complex	NAS	9601641
GO:0031122	Process	Cytoplasmic microtubule organization	IEA
GO:0031398	Process	Positive regulation of protein ubiquitination	IEA
GO:0031398	Process	Positive regulation of protein ubiquitination	IMP	16601693
GO:0031410	Component	Cytoplasmic vesicle	IEA
GO:0031410	Component	Cytoplasmic vesicle	ISS
GO:0031625	Function	Ubiquitin protein ligase binding	IBA
GO:0031625	Function	Ubiquitin protein ligase binding	IEA
GO:0031625	Function	Ubiquitin protein ligase binding	IPI	16601693, 21478859
GO:0032436	Process	Positive regulation of proteasomal ubiquitin-dependent protein catabolic process	IBA
GO:0032436	Process	Positive regulation of proteasomal ubiquitin-dependent protein catabolic process	IEA
GO:0032991	Component	Protein-containing complex	IEA
GO:0034244	Process	Negative regulation of transcription elongation by RNA polymerase II	IEA
GO:0035591	Function	Signaling adaptor activity	IEA
GO:0035591	Function	Signaling adaptor activity	TAS	21799911
GO:0036342	Process	Post-anal tail morphogenesis	IEA
GO:0042802	Function	Identical protein binding	IBA
GO:0042802	Function	Identical protein binding	IEA
GO:0042802	Function	Identical protein binding	IPI	10811618, 16169070, 21245303
GO:0042802	Function	Identical protein binding	ISS
GO:0042803	Function	Protein homodimerization activity	IEA
GO:0042803	Function	Protein homodimerization activity	ISS
GO:0043161	Process	Proteasome-mediated ubiquitin-dependent protein catabolic process	NAS	9601641
GO:0043539	Function	Protein serine/threonine kinase activator activity	IDA	9601641
GO:0044725	Process	Epigenetic programming in the zygotic pronuclei	IEA
GO:0045599	Process	Negative regulation of fat cell differentiation	IEA
GO:0045732	Process	Positive regulation of protein catabolic process	IC	16188939
GO:0045732	Process	Positive regulation of protein catabolic process	IDA	9601641
GO:0046330	Process	Positive regulation of JNK cascade	IEA
GO:0046330	Process	Positive regulation of JNK cascade	ISS
GO:0046332	Function	SMAD binding	IPI	18593713
GO:0048318	Process	Axial mesoderm development	IEA
GO:0048320	Process	Axial mesoderm formation	IEA
GO:0048468	Process	Cell development	IBA
GO:0048471	Component	Perinuclear region of cytoplasm	IDA	19038973
GO:0051248	Process	Negative regulation of protein metabolic process	IEA
GO:0060070	Process	Canonical Wnt signaling pathway	IEA
GO:0060090	Function	Molecular adaptor activity	IBA
GO:0060090	Function	Molecular adaptor activity	IDA	9601641, 21087614
GO:0060322	Process	Head development	IEA
GO:0060828	Process	Regulation of canonical Wnt signaling pathway	IEA
GO:0065003	Process	Protein-containing complex assembly	IDA	16601693
GO:0070016	Function	Armadillo repeat domain binding	ISS
GO:0070411	Function	I-SMAD binding	IBA
GO:0070411	Function	I-SMAD binding	IEA
GO:0070411	Function	I-SMAD binding	IPI	16601693, 18593713
GO:0070412	Function	R-SMAD binding	IEA
GO:0071944	Component	Cell periphery	IDA	19038973
GO:0090090	Process	Negative regulation of canonical Wnt signaling pathway	IBA
GO:0090090	Process	Negative regulation of canonical Wnt signaling pathway	IC	9601641
GO:0090090	Process	Negative regulation of canonical Wnt signaling pathway	IDA	10644691
GO:0090090	Process	Negative regulation of canonical Wnt signaling pathway	IEA
GO:0090090	Process	Negative regulation of canonical Wnt signaling pathway	IEA
GO:0090090	Process	Negative regulation of canonical Wnt signaling pathway	IMP	22899650
GO:0120283	Function	Protein serine/threonine kinase binding	IPI	18593713
GO:1904885	Process	Beta-catenin destruction complex assembly	IDA	18593713
GO:1990756	Function	Ubiquitin-like ligase-substrate adaptor activity	IEA
GO:1990756	Function	Ubiquitin-like ligase-substrate adaptor activity	IMP	16601693
GO:1990909	Component	Wnt signalosome	IEA
GO:2000060	Process	Positive regulation of ubiquitin-dependent protein catabolic process	IEA
GO:2000060	Process	Positive regulation of ubiquitin-dependent protein catabolic process	ISS

Other IDs

• MIM: 603816
• HGNC: 903
• e!Ensembl: ENSG00000103126

Protein

• UniProt ID: O15169
• Protein name: Axin-1 (Axis inhibition protein 1) (hAxin)
• Protein 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, PubMed:28829046). Controls dorsoventral patternin
• PDB: 1DK8, 1EMU, 1O9U, 3ZDI, 4B7T, 4NM0, 4NM3, 4NM5, 4NM7, 4NU1, 5WZZ, 6JCK, 7SXF, 7SXG, 7SXH, 7SXJ, 7Y1P, 8RU3, 8RU4, 8VMG
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF16646	AXIN1_TNKS_BD	8 → 80	Axin-1 tankyrase binding domain	Disordered
  PF00615	RGS	88 → 210	Regulator of G protein signaling domain	Domain
  PF08833	Axin_b-cat_bind	465 → 498	Axin beta-catenin binding motif	Motif
  PF00778	DIX	781 → 860	DIX domain	Family

• Tissue specificity: TISSUE SPECIFICITY: Ubiquitously expressed.
• Sequence:

  MNIQEQGFPLDLGASFTEDAPRPPVPGEEGELVSTDPRPASYSFCSGKGVGIKGETSTAT
  PRRSDLDLGYEPEGSASPTPPYLKWAESLHSLLDDQDGISLFRTFLKQEGCADLLDFWFA
  CTGFRKLEPCDSNEEKRLKLARAIYRKYILDNNGIVSRQTKPATKSFIKGCIMKQLIDPA
  MFDQAQTEIQATMEENTYPSFLKSDIYLEYTRTGSESPKVCSDQSSGSGTGKGISGYLPT
  LNEDEEWKCDQDMDEDDGRDAAPPGRLPQKLLLETAAPRVSSSRRYSEGREFRYGSWREP
  VNPYYVNAGYALAPATSANDSEQQSLSSDADTLSLTDSSVDGIPPYRIRKQHRREMQESV
  QVNGRVPLPHIPRTYRVPKEVRVEPQKFAEELIHRLEAVQRTREAEEKLEERLKRVRMEE
  EGEDGDPSSGPPGPCHKLPPAPAWHHFPPRCVDMGCAGLRDAHEENPESILDEHVQRVLR
  TPGRQSPGPGHRSPDSGHVAKMPVALGGAASGHGKHVPKSGAKLDAAGLHHHRHVHHHVH
  HSTARPKEQVEAEATRRAQSSFAWGLEPHSHGARSRGYSESVGAAPNASDGLAHSGKVGV
  ACKRNAKKAESGKSASTEVPGASEDAEKNQKIMQWIIEGEKEISRHRRTGHGSSGTRKPQ
  PHENSRPLSLEHPWAGPQLRTSVQPSHLFIQDPTMPPHPAPNPLTQLEEARRRLEEEEKR
  ASRAPSKQRYVQEVMRRGRACVRPACAPVLHVVPAVSDMELSETETRSQRKVGGGSAQPC
  DSIVVAYYFCGEPIPYRTLVRGRAVTLGQFKELLTKKGSYRYYFKKVSDEFDCGVVFEEV
  REDEAVLPVFEEKIIGKVEKVD

• Sequence length: 862

Pathways

KEGG:

Wnt signaling pathway
Hippo signaling pathway
Signaling pathways regulating pluripotency of stem cells
Cushing syndrome
Alzheimer disease
Pathways of neurodegeneration - multiple diseases
Human papillomavirus infection
Pathways in cancer
Colorectal cancer
Endometrial cancer
Basal cell carcinoma
Breast cancer
Hepatocellular carcinoma
Gastric cancer

Reactome:

Degradation of beta-catenin by the destruction complex
Beta-catenin phosphorylation cascade
TCF dependent signaling in response to WNT
Degradation of AXIN
Disassembly of the destruction complex and recruitment of AXIN to the membrane
Misspliced GSK3beta mutants stabilize beta-catenin
S33 mutants of beta-catenin aren't phosphorylated
S37 mutants of beta-catenin aren't phosphorylated
S45 mutants of beta-catenin aren't phosphorylated
T41 mutants of beta-catenin aren't phosphorylated
APC truncation mutants have impaired AXIN binding
AXIN missense mutants destabilize the destruction complex
Truncations of AMER1 destabilize the destruction complex
Ub-specific processing proteases
RUNX1 regulates estrogen receptor mediated transcription
RUNX1 regulates transcription of genes involved in WNT signaling
Estrogen-dependent gene expression

Associated diseases

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Craniometadiaphyseal osteosclerosis with hip dysplasia	Pathogenic	rs2548491182, rs370661416	RCV003388225 RCV003388227
Hepatocellular carcinoma	Pathogenic	rs587776627	RCV000006408

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
AXIN1-related disorder	Likely benign; Benign	rs150141520, rs769686933, rs1805102, rs118063900, rs141481399, rs966557459, rs116350678, rs1200388281, rs768762328, rs758547828, rs568525212, rs749294095, rs374978030, rs113073289, rs149536239, rs139163339, rs79781539, rs115321780	RCV003921703 RCV003981725 RCV003911797 RCV003979330 RCV003941931 RCV003963933 RCV003981230 RCV003959261 RCV003914551 RCV003956861 RCV003964749 RCV003976937 RCV003971837 RCV003933295 RCV003926063 RCV003970679 RCV003978366 RCV004758064
Caudal duplication	Benign; Likely benign	rs34015754, rs113073289	RCV002502961 RCV002489301
EBV-positive nodal T- and NK-cell lymphoma	Likely benign	rs2141476400	RCV004557877

Associations from Text Mining
Disease Name	Relationship Type	References
Adenocarcinoma Mucinous	Associate	26894286
Adenoma	Inhibit	27462886
Adenoma	Associate	29496310
Adenomatous Polyposis Coli	Associate	18076571, 22761442, 27482906, 28731177, 30072583, 9601641, 9734785
Adenomatous Polyposis Coli	Stimulate	32626748
Alzheimer Disease	Stimulate	39929297
Asthma	Associate	37802634
Asthma	Inhibit	40595623
Bicuspid Aortic Valve Disease	Associate	20098615
Breast Neoplasms	Associate	28055379
Carcinogenesis	Associate	10575011, 12771989, 25502816, 35780128
Carcinoma Adenoid Cystic	Associate	15195113
Carcinoma Hepatocellular	Associate	22524844, 25021421, 25159915, 25822088, 27851986, 31173963, 31514071, 33407585, 33811251, 36517508, 38359148
Carcinoma Non Small Cell Lung	Inhibit	31143301
Carcinoma Non Small Cell Lung	Associate	33506901, 38233113, 39308524
Carcinoma Ovarian Epithelial	Associate	30929455
Cartilage Diseases	Associate	31366320
Cholangiocarcinoma	Inhibit	37832404
Colorectal Neoplasms	Associate	10318916, 23661344, 25222838, 26820603, 26894286, 27462886, 28100566, 28731177, 28865443, 29505855, 31723073, 32958699, 36129915, 9734785
Diabetes Mellitus	Associate	35504843
Double Outlet Right Ventricle	Associate	34204335
Dyskinesias	Associate	34564680
Ectodermal Dysplasia	Associate	21416598
Esophageal Squamous Cell Carcinoma	Associate	12771989
Fever	Inhibit	40595623
Fibromyalgia	Associate	35693781
Gastroesophageal Reflux	Associate	14970870
Heart Defects Congenital	Associate	33096676
Infections	Inhibit	40595623
Inflammation	Associate	35693781
Leukemia Lymphocytic Chronic B Cell	Associate	30038380
Leukemia Lymphoma Adult T Cell	Associate	33562071
Leukemia Myelogenous Chronic BCR ABL Positive	Associate	15306667
Leukoencephalopathies	Associate	34911837
Lung Neoplasms	Inhibit	23192643
Lung Neoplasms	Associate	32051824
Lymphatic Metastasis	Inhibit	12771989
Lymphatic Metastasis	Associate	23192643, 31723073
Medulloblastoma	Associate	33978203
Melanoma	Associate	22234612, 22895053, 23869245, 35561126
Neoplasm Metastasis	Inhibit	16772034
Neoplasms	Inhibit	11500377, 11943708, 12771989, 15082903, 15526030, 19633924, 21087614, 28055379, 32958699, 35561126, 36510340
Neoplasms	Associate	14970870, 16772034, 17897439, 18172167, 22761442, 25526364, 26894286, 30072583, 32761426, 33811251, 36129915, 36510340, 38359148, 39308524
Neoplasms Neuroepithelial	Associate	19633924
Non Muscle Invasive Bladder Neoplasms	Associate	31143301
Osteoporosis	Associate	37380960
Osteosarcoma	Associate	19888226
Parkinson Disease	Associate	38272954
Pneumonia	Inhibit	40595623
Respiratory Tract Infections	Inhibit	40595623
Retinal Dysplasia	Associate	34564680
Squamous Cell Carcinoma of Head and Neck	Associate	21393552, 34564680
Stomach Diseases	Associate	18330950
Stomach Neoplasms	Associate	18330950, 37973999
Thyroid Cancer Papillary	Associate	36510340
Tonsillitis	Inhibit	40595623
Urinary Bladder Neoplasms	Inhibit	31143301
Urinary Bladder Neoplasms	Associate	31143301
Uterine Cervical Neoplasms	Associate	27577083
Warts	Associate	31569353