ALX1 (ALX homeobox 1)

Gene

• Entrez ID: 8092
• Gene name: ALX homeobox 1
• Gene symbol: ALX1
• Synonyms (NCBI Gene): CART1, FND3, HEL23
• Chromosome: 12
• Chromosome location: 12q21.31
• Summary: The specific function of this gene has yet to be determined in humans; however, in rodents, it is necessary for survival of the forebrain mesenchyme and may also be involved in development of the cervix. Mutations in the mouse gene lead to neural tube

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs587776684	G>A	Pathogenic	Splice donor variant
rs1593055101	G>C	Pathogenic	Splice acceptor variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT029276	hsa-miR-26b-5p	Microarray	19088304
MIRT613331	hsa-miR-8485	HITS-CLIP	19536157
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT669536	hsa-miR-7854-3p	HITS-CLIP	23824327
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT530201	hsa-miR-4635	PAR-CLIP	20371350
MIRT530199	hsa-miR-197-3p	PAR-CLIP	20371350
MIRT530198	hsa-miR-7843-3p	PAR-CLIP	20371350
MIRT530197	hsa-miR-127-5p	PAR-CLIP	20371350
MIRT530196	hsa-miR-455-3p	PAR-CLIP	20371350
MIRT530195	hsa-miR-6516-5p	PAR-CLIP	20371350
MIRT530203	hsa-miR-4421	PAR-CLIP	22012620
MIRT530202	hsa-miR-5699-3p	PAR-CLIP	22012620
MIRT530201	hsa-miR-4635	PAR-CLIP	22012620
MIRT530200	hsa-miR-431-5p	PAR-CLIP	22012620
MIRT530199	hsa-miR-197-3p	PAR-CLIP	22012620
MIRT530198	hsa-miR-7843-3p	PAR-CLIP	22012620
MIRT530197	hsa-miR-127-5p	PAR-CLIP	22012620
MIRT530196	hsa-miR-455-3p	PAR-CLIP	22012620
MIRT530195	hsa-miR-6516-5p	PAR-CLIP	22012620
MIRT450074	hsa-miR-3662	PAR-CLIP	22100165
MIRT450073	hsa-miR-1252-3p	PAR-CLIP	22100165
MIRT450072	hsa-miR-3975	PAR-CLIP	22100165
MIRT450071	hsa-miR-2467-5p	PAR-CLIP	22100165
MIRT450070	hsa-miR-485-5p	PAR-CLIP	22100165
MIRT450068	hsa-miR-6884-5p	PAR-CLIP	22100165
MIRT450069	hsa-miR-3188	PAR-CLIP	22100165
MIRT530197	hsa-miR-127-5p	PAR-CLIP	27292025
MIRT530197	hsa-miR-127-5p	PAR-CLIP	27292025
MIRT530197	hsa-miR-127-5p	PAR-CLIP	27292025
MIRT530197	hsa-miR-127-5p	PAR-CLIP	27292025
MIRT530199	hsa-miR-197-3p	PAR-CLIP	27292025
MIRT530199	hsa-miR-197-3p	PAR-CLIP	27292025
MIRT530199	hsa-miR-197-3p	PAR-CLIP	27292025
MIRT530199	hsa-miR-197-3p	PAR-CLIP	27292025
MIRT530196	hsa-miR-455-3p	PAR-CLIP	27292025
MIRT530196	hsa-miR-455-3p	PAR-CLIP	27292025
MIRT530196	hsa-miR-455-3p	PAR-CLIP	27292025
MIRT530201	hsa-miR-4635	PAR-CLIP	27292025
MIRT530201	hsa-miR-4635	PAR-CLIP	27292025
MIRT530201	hsa-miR-4635	PAR-CLIP	27292025
MIRT530201	hsa-miR-4635	PAR-CLIP	27292025
MIRT530195	hsa-miR-6516-5p	PAR-CLIP	27292025
MIRT530195	hsa-miR-6516-5p	PAR-CLIP	27292025
MIRT530195	hsa-miR-6516-5p	PAR-CLIP	27292025
MIRT530198	hsa-miR-7843-3p	PAR-CLIP	27292025
MIRT530198	hsa-miR-7843-3p	PAR-CLIP	27292025
MIRT530198	hsa-miR-7843-3p	PAR-CLIP	27292025
MIRT530198	hsa-miR-7843-3p	PAR-CLIP	27292025
MIRT613331	hsa-miR-8485	HITS-CLIP	27418678
MIRT736558	hsa-miR-192-5p	Luciferase reporter assay, Western blotting, qRT-PCR	34104082
MIRT613331	hsa-miR-8485	HITS-CLIP	19536157
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT669536	hsa-miR-7854-3p	HITS-CLIP	23824327
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT613331	hsa-miR-8485	HITS-CLIP	23824327
MIRT530201	hsa-miR-4635	PAR-CLIP	20371350
MIRT530199	hsa-miR-197-3p	PAR-CLIP	20371350
MIRT530198	hsa-miR-7843-3p	PAR-CLIP	20371350
MIRT530197	hsa-miR-127-5p	PAR-CLIP	20371350
MIRT530196	hsa-miR-455-3p	PAR-CLIP	20371350
MIRT530195	hsa-miR-6516-5p	PAR-CLIP	20371350
MIRT530203	hsa-miR-4421	PAR-CLIP	22012620
MIRT530202	hsa-miR-5699-3p	PAR-CLIP	22012620
MIRT530201	hsa-miR-4635	PAR-CLIP	22012620
MIRT530200	hsa-miR-431-5p	PAR-CLIP	22012620
MIRT530199	hsa-miR-197-3p	PAR-CLIP	22012620
MIRT530198	hsa-miR-7843-3p	PAR-CLIP	22012620
MIRT530197	hsa-miR-127-5p	PAR-CLIP	22012620
MIRT530196	hsa-miR-455-3p	PAR-CLIP	22012620
MIRT530195	hsa-miR-6516-5p	PAR-CLIP	22012620
MIRT450074	hsa-miR-3662	PAR-CLIP	22100165
MIRT450073	hsa-miR-1252-3p	PAR-CLIP	22100165
MIRT450072	hsa-miR-3975	PAR-CLIP	22100165
MIRT450071	hsa-miR-2467-5p	PAR-CLIP	22100165
MIRT450070	hsa-miR-485-5p	PAR-CLIP	22100165
MIRT450068	hsa-miR-6884-5p	PAR-CLIP	22100165
MIRT450069	hsa-miR-3188	PAR-CLIP	22100165
MIRT779408	hsa-miR-1278	CLIP-seq
MIRT779409	hsa-miR-4729	CLIP-seq
MIRT2473473	hsa-miR-4752	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IDA	8756334
GO:0000785	Component	Chromatin	ISA
GO:0000977	Function	RNA polymerase II transcription regulatory region sequence-specific DNA binding	IBA
GO:0000977	Function	RNA polymerase II transcription regulatory region sequence-specific DNA binding	IDA	9753625
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IEA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IBA
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IDA	9753625
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	TAS	8756334
GO:0001843	Process	Neural tube closure	IEA
GO:0003677	Function	DNA binding	IEA
GO:0003700	Function	DNA-binding transcription factor activity	IEA
GO:0005515	Function	Protein binding	IPI	16189514, 32296183
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IDA	9753625, 23288509
GO:0005634	Component	Nucleus	IEA
GO:0005654	Component	Nucleoplasm	IDA
GO:0005667	Component	Transcription regulator complex	IEA
GO:0005794	Component	Golgi apparatus	IDA
GO:0006355	Process	Regulation of DNA-templated transcription	IEA
GO:0009952	Process	Anterior/posterior pattern specification	IEA
GO:0010718	Process	Positive regulation of epithelial to mesenchymal transition	IMP	23288509
GO:0014031	Process	Mesenchymal cell development	IEA
GO:0016604	Component	Nuclear body	IDA
GO:0030326	Process	Embryonic limb morphogenesis	IEA
GO:0043565	Function	Sequence-specific DNA binding	IEA
GO:0045892	Process	Negative regulation of DNA-templated transcription	IBA
GO:0045893	Process	Positive regulation of DNA-templated transcription	IDA	9753625
GO:0045893	Process	Positive regulation of DNA-templated transcription	IMP	23288509
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IBA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	9753625
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IEA
GO:0048666	Process	Neuron development	IBA
GO:0048704	Process	Embryonic skeletal system morphogenesis	IBA
GO:0048704	Process	Embryonic skeletal system morphogenesis	IEA
GO:0048864	Process	Stem cell development	IEA
GO:0060021	Process	Roof of mouth development	IEA
GO:1990837	Function	Sequence-specific double-stranded DNA binding	IDA	28473536
GO:1990837	Function	Sequence-specific double-stranded DNA binding	IEA

Other IDs

• MIM: 601527
• HGNC: 1494
• e!Ensembl: ENSG00000180318

Protein

• UniProt ID: Q15699
• Protein name: ALX homeobox protein 1 (Cartilage homeoprotein 1) (CART-1)
• Protein function: Sequence-specific DNA-binding transcription factor that binds palindromic sequences within promoters and may activate or repress the transcription of a subset of genes (PubMed:8756334, PubMed:9753625). Most probably regulates the expression of g
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00046	Homeodomain	133 → 189	Homeodomain	Domain
  PF03826	OAR	302 → 320	OAR motif	Motif

• Tissue specificity: TISSUE SPECIFICITY: Cartilage and cervix tissue. {ECO:0000269|PubMed:8756334}.
• Sequence:

  MEFLSEKFALKSPPSKNSDFYMGAGGPLEHVMETLDNESFYSKASAGKCVQAFGPLPRAE
  HHVRLERTSPCQDSSVNYGITKVEGQPLHTELNRAMDNCNSLRMSPVKGMQEKGELDELG
  DKCDSNVSSSKKRRHRTTFTSLQLEELEKVFQKTHYPDVYVREQLALRTELTEARVQVWF
  QNRRAKWRKRERYGQIQQAKSHFAATYDISVLPRTDSYPQIQNNLWAGNASGGSVVTSCM
  LPRDTSSCMTPYSHSPRTDSSYTGFSNHQNQFSHVPLNNFFTDSLLTGATNGHAFETKPE
  FERRSSSIAVLRMKAKEHTANISWAM

• Sequence length: 326

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Frontonasal dysplasia - severe microphthalmia - severe facial clefting syndrome	Pathogenic; Likely pathogenic	rs587776684, rs781138367, rs1593055101	RCV000008579 RCV003314275 RCV001027524	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ALX1-related disorder	Conflicting classifications of pathogenicity; Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CRANIOFACIAL ABNORMALITIES	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DESBUQUOIS SYNDROME	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
FRONTONASAL DYSPLASIA	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
FRONTONASAL DYSPLASIA 3	—	Disgenet, HPO Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
FRONTONASAL DYSPLASIA, SEVERE MICROPHTHALMIA, SEVERE FACIAL CLEFTING SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
FRONTONASAL DYSPLASIA-SEVERE MICROPHTHALMIA-SEVERE FACIAL CLEFTING SYNDROME	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung adenocarcinoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Absent eyebrow	Absent eyebrow	HPO_DG			★☆☆☆☆ Found in Text Mining only
Acrania	Acrania	BEFREE	8673125		★☆☆☆☆ Found in Text Mining only
Agenesis of corpus callosum	Agenesis Of Corpus Callosum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Blepharoptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Brachycephaly	Brachycephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Brachydactyly	Brachydactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	7592751, 8752152		★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	26722397, 28069692	Associate	★☆☆☆☆ Found in Text Mining only
Cataract	Cataract	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cervix carcinoma	Cervix carcinoma	BEFREE	8756334		★☆☆☆☆ Found in Text Mining only
Chondrosarcoma	Chondrosarcoma	BEFREE	8756334		★☆☆☆☆ Found in Text Mining only
Clinodactyly of fingers	Clinodactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Conductive hearing loss	Hearing Loss	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital Epicanthus	Congenital Epicanthus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Craniofrontonasal dysplasia	Craniofrontonasal Dysplasia	BEFREE	24376213		★☆☆☆☆ Found in Text Mining only
Craniosynostosis	Craniosynostosis	BEFREE	24376213		★☆☆☆☆ Found in Text Mining only
Dystonic Disorders	Dystonia	Pubtator	20451171	Associate	★☆☆☆☆ Found in Text Mining only
Exencephaly	Anencephaly	BEFREE	19117321		★☆☆☆☆ Found in Text Mining only
Frontonasal dysplasia	Frontonasal Dysplasia	BEFREE	20451171, 24376213, 27324866		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Frontonasal dysplasia	Frontonasal dysplasia	Pubtator	20451171	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Frontonasal dysplasia	Frontonasal Dysplasia	GENOMICS_ENGLAND_DG	27324866		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Frontonasal dysplasia	Frontonasal Dysplasia	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
FRONTONASAL DYSPLASIA 3	Frontonasal Dysplasia	GENOMICS_ENGLAND_DG	20451171, 23059813, 26610632		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
FRONTONASAL DYSPLASIA 3	Frontonasal Dysplasia	ORPHANET_DG	20451171		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
FRONTONASAL DYSPLASIA 3	Frontonasal Dysplasia	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Frontonasal dysplasia, severe microphthalmia, severe facial clefting syndrome	Frontonasal Dysplasia, Severe Microphthalmia, Severe Facial Clefting Syndrome	GENOMICS_ENGLAND_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Frontonasal dysplasia-severe microphthalmia-severe facial clefting syndrome	Frontonasal Dysplasia, Severe Microphthalmia, Severe Facial Clefting Syndrome	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypoplasia of the maxilla	Hypoplasia of the maxilla	HPO_DG			★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Lipoma of corpus callosum	Lipoma of corpus callosum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Lung neoplasms	Pubtator	26722397	Associate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	8752152		★☆☆☆☆ Found in Text Mining only
Melanoma	Melanoma	Pubtator	26489459	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
melanoma	Melanoma	BEFREE	30773258		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Microphthalmos	Microphthalmos	BEFREE	20451171		★☆☆☆☆ Found in Text Mining only
Microphthalmos	Microphthalmos	Pubtator	20451171	Associate	★☆☆☆☆ Found in Text Mining only
Microphthalmos	Microphthalmos	HPO_DG			★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	8756334		★☆☆☆☆ Found in Text Mining only
Neural Tube Defects	Neural Tube Defect	BEFREE	15800852, 20932315		★☆☆☆☆ Found in Text Mining only
Osteosarcoma	Osteosarcoma	BEFREE	25736924		★☆☆☆☆ Found in Text Mining only
PARIETAL FORAMINA	Parietal Foramina	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Spina Bifida Cystica	Spina Bifida Cystica	BEFREE	19117321		★☆☆☆☆ Found in Text Mining only
Tetralogy of Fallot	Tetralogy of Fallot	HPO_DG			★☆☆☆☆ Found in Text Mining only