ALX3 (ALX homeobox 3)

Gene

• Entrez ID: 257
• Gene name: ALX homeobox 3
• Gene symbol: ALX3
• Synonyms (NCBI Gene): FND, FND1
• Chromosome: 1
• Chromosome location: 1p13.3
• Summary: This gene encodes a nuclear protein with a homeobox DNA-binding domain that functions as a transcriptional regulator involved in cell-type differentiation and development. Preferential methylation of this gene`s promoter is associated with advanced-stage

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs121908166	T>C	Pathogenic	Missense variant, coding sequence variant
rs121908167	G>C	Pathogenic	Missense variant, coding sequence variant
rs121908168	G>A	Pathogenic	Missense variant, coding sequence variant
rs121908169	A>T	Pathogenic	Stop gained, coding sequence variant
rs121908170	G>A	Pathogenic	Missense variant, coding sequence variant
rs387906319	TCAG>-	Pathogenic	Coding sequence variant, frameshift variant
rs1553196068	AG>-	Likely-pathogenic	Frameshift variant, coding sequence variant
rs1570936479	T>A	Pathogenic	Splice acceptor variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT779410	hsa-miR-1587	CLIP-seq
MIRT779411	hsa-miR-1827	CLIP-seq
MIRT779412	hsa-miR-2467-3p	CLIP-seq
MIRT779413	hsa-miR-3192	CLIP-seq
MIRT779414	hsa-miR-3612	CLIP-seq
MIRT779415	hsa-miR-4257	CLIP-seq
MIRT779416	hsa-miR-4300	CLIP-seq
MIRT779417	hsa-miR-4417	CLIP-seq
MIRT779418	hsa-miR-4443	CLIP-seq
MIRT779419	hsa-miR-4492	CLIP-seq
MIRT779420	hsa-miR-4498	CLIP-seq
MIRT779421	hsa-miR-4505	CLIP-seq
MIRT779422	hsa-miR-4656	CLIP-seq
MIRT779423	hsa-miR-4675	CLIP-seq
MIRT779424	hsa-miR-4741	CLIP-seq
MIRT779425	hsa-miR-541	CLIP-seq
MIRT779426	hsa-miR-650	CLIP-seq
MIRT779427	hsa-miR-654-5p	CLIP-seq
MIRT779428	hsa-miR-762	CLIP-seq
MIRT779429	hsa-miR-920	CLIP-seq
MIRT1930032	hsa-miR-3660	CLIP-seq
MIRT1930033	hsa-miR-4526	CLIP-seq
MIRT1930034	hsa-miR-4645-3p	CLIP-seq
MIRT1930035	hsa-miR-637	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000785	Component	Chromatin	ISA
GO:0000977	Function	RNA polymerase II transcription regulatory region sequence-specific DNA binding	IBA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IBA
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:0003677	Function	DNA binding	IEA
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IEA
GO:0006355	Process	Regulation of DNA-templated transcription	IEA
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA
GO:0007389	Process	Pattern specification process	IEA
GO:0035115	Process	Embryonic forelimb morphogenesis	IEA
GO:0035116	Process	Embryonic hindlimb morphogenesis	IEA
GO:0042981	Process	Regulation of apoptotic process	IEA
GO:0048666	Process	Neuron development	IBA
GO:0048704	Process	Embryonic skeletal system morphogenesis	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: 606014
• HGNC: 449
• e!Ensembl: ENSG00000156150

Protein

• UniProt ID: O95076
• Protein name: Homeobox protein aristaless-like 3 (Proline-rich transcription factor ALX3)
• Protein function: Transcriptional regulator with a possible role in patterning of mesoderm during development.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00046	Homeodomain	154 → 210	Homeodomain	Domain

• Sequence:

  MDPEHCAPFRVGPAPGPYVASGDEPPGPQGTPAAAPHLHPAPPRGPRLTRFPACGPLEPY
  LPEPAKPPAKYLQDLGPGPALNGGHFYEGPAEAEEKTSKAASFPQLPLDCRGGPRDGPSN
  LQGSPGPCLASLHLPLSPGLPDSMELAKNKSKKRRNRTTFSTFQLEELEKVFQKTHYPDV
  YAREQLALRTDLTEARVQVWFQNRRAKWRKRERYGKIQEGRNPFTAAYDISVLPRTDSHP
  QLQNSLWASPGSGSPGGPCLVSPEGIPSPCMSPYSHPHGSVAGFMGVPAPSAAHPGIYSI
  HGFPPTLGGHSFEPSSDGDYKSPSLVSLRVKPKEPPGLLNWTT

• Sequence length: 343

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
Frontorhiny	Pathogenic; Likely pathogenic	rs1570936479, rs121908166, rs121908167, rs121908169, rs387906319, rs121908170, rs2524436550, rs1553196068	RCV000004905 RCV000004906 RCV000004907 RCV000004909 RCV000004910 RCV000004911 RCV004006260 RCV000677633	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ALX3-related disorder	Benign; Likely benign	ClinVar	★★☆☆☆ 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 1	—	HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEURAL TUBE DEFECT, FOLATE-SENSITIVE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEURAL TUBE DEFECTS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEURAL TUBE DEFECTS X-LINKED	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OPEN-ANGLE GLAUCOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Agenesis of corpus callosum	Agenesis Of Corpus Callosum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Anterior basal encephalocele	Basal encephalocele	HPO_DG			★☆☆☆☆ Found in Text Mining only
Basal encephalocele	Basal encephalocele	HPO_DG			★☆☆☆☆ Found in Text Mining only
Blepharoptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Brachydactyly	Brachydactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	30875375		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	30875375	Inhibit	★☆☆☆☆ Found in Text Mining only
Cataract	Cataract	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cleft Palate	Cleft palate	Pubtator	19401770	Associate	★☆☆☆☆ Found in Text Mining only
Clinodactyly	Clinodactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Clinodactyly of fingers	Clinodactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Colon Carcinoma	Colon Carcinoma	BEFREE	30875375		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	21636702		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	21636702	Associate	★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	30875375	Inhibit	★☆☆☆☆ Found in Text Mining only
Conductive hearing loss	Hearing Loss	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital arteriovenous malformation	Congenital Arteriovenous Malformation	BEFREE	30952115		★☆☆☆☆ Found in Text Mining only
Congenital Camptodactyly	Congenital Camptodactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital cerebral hernia	Congenital Cerebral Hernia	BEFREE	17955515		★☆☆☆☆ Found in Text Mining only
Congenital coloboma of iris	Congenital Coloboma Of Iris	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital conductive hearing loss	Congenital conductive hearing impairment	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital Epicanthus	Congenital Epicanthus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital neurologic anomalies	Drachtman Weinblatt Sitarz syndrome	BEFREE	19365836		★☆☆☆☆ Found in Text Mining only
Congenital ocular coloboma (disorder)	Congenital ocular coloboma	BEFREE	1700608		★☆☆☆☆ Found in Text Mining only
Congenital ocular coloboma (disorder)	Congenital ocular coloboma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Craniofrontonasal dysplasia	Craniofrontonasal Dysplasia	BEFREE	2225532, 24376213		★☆☆☆☆ Found in Text Mining only
Cranioschisis	Anencephaly	BEFREE	17955515		★☆☆☆☆ Found in Text Mining only
Craniosynostosis	Craniosynostosis	BEFREE	24376213		★☆☆☆☆ Found in Text Mining only
Dermoid Cyst	Dermoid Cyst	HPO_DG			★☆☆☆☆ Found in Text Mining only
Diabetes Insipidus	Diabetes Insipidus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dysautonomia	Dysautonomia	BEFREE	30344497		★☆☆☆☆ Found in Text Mining only
Dysostoses	Dysostoses	BEFREE	10564879		★☆☆☆☆ Found in Text Mining only
Encephalocele	Encephalocele	BEFREE	17955515		★☆☆☆☆ Found in Text Mining only
Frontonasal dysplasia	Frontonasal Dysplasia	GENOMICS_ENGLAND_DG	15127764, 19401770, 19409524		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Frontonasal dysplasia	Frontonasal Dysplasia	BEFREE	19409524, 23637006, 24376213, 27324866, 29215096, 7363499		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Frontonasal dysplasia	Frontonasal Dysplasia	UNIPROT_DG	19409524		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Frontonasal dysplasia	Frontonasal Dysplasia	ORPHANET_DG	19409524		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Frontonasal dysplasia	Frontonasal dysplasia	Pubtator	19409524	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Frontonasal dysplasia	Frontonasal Dysplasia	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Frontonasal dysplasia	Frontonasal Dysplasia	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Frontorhiny	Frontorhiny	Orphanet			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Hyperglycemia	Hyperglycemia	BEFREE	28341857		★☆☆☆☆ Found in Text Mining only
Hypopituitarism	Hypopituitarism	HPO_DG			★☆☆☆☆ Found in Text Mining only
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
Learning Disabilities	Learning Disorders	BEFREE	17955515		★☆☆☆☆ Found in Text Mining only
Lipoma of corpus callosum	Lipoma of corpus callosum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	30875375		★☆☆☆☆ Found in Text Mining only
Malignant tumor of colon	Colonic Neoplasms	BEFREE	30875375		★☆☆☆☆ Found in Text Mining only
Microphthalmos	Microphthalmos	HPO_DG			★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	30875375		★☆☆☆☆ Found in Text Mining only
Neural Tube Defects	Neural Tube Defect	BEFREE	28341857		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Neuroblastoma	Neuroblastoma	BEFREE	11807986		★☆☆☆☆ Found in Text Mining only
Oestrogen receptor positive breast cancer	Oestrogen Receptor Positive Breast Cancer	BEFREE	30875375		★☆☆☆☆ Found in Text Mining only
PARIETAL FORAMINA	Parietal Foramina	HPO_DG			★☆☆☆☆ Found in Text Mining only
Polydactyly	Polydactyly	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
Ptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Rhabdomyosarcoma	Rhabdomyosarcoma	Pubtator	22419069	Associate	★☆☆☆☆ Found in Text Mining only
Scoliosis, unspecified	Scoliosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Strabismus	Strabismus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Tetralogy of Fallot	Tetralogy of Fallot	HPO_DG			★☆☆☆☆ Found in Text Mining only
Triple Negative Breast Neoplasms	Triple Negative Breast Neoplasms	BEFREE	30875375		★☆☆☆☆ Found in Text Mining only
Ulnar polydactyly of fingers	Postaxial hand polydactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only