HOXA2 (homeobox A2)

Gene

• Entrez ID: 3199
• Gene name: Homeobox A2
• Gene symbol: HOXA2
• Synonyms (NCBI Gene): HOX1K, MCOHI
• Chromosome: 7
• Chromosome location: 7p15.2
• Summary: In vertebrates, the genes encoding the class of transcription factors called homeobox genes are found in clusters named A, B, C, and D on four separate chromosomes. Expression of these proteins is spatially and temporally regulated during embryonic develo

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs119489104	G>T	Pathogenic	Missense variant, coding sequence variant
rs398122360	G>A	Pathogenic	Stop gained, coding sequence variant
rs1554334301	C>A	Pathogenic	Coding sequence variant, stop gained

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT017046	hsa-miR-335-5p	Microarray	18185580
MIRT1549597	hsa-miR-2052	CLIP-seq
MIRT1549597	hsa-miR-2052	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
CHD8	Unknown	20085832

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IEA
GO:0000785	Component	Chromatin	ISA
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IEA
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:0001227	Function	DNA-binding transcription repressor activity, RNA polymerase II-specific	IEA
GO:0001709	Process	Cell fate determination	IEA
GO:0002076	Process	Osteoblast development	IEA
GO:0003677	Function	DNA binding	IEA
GO:0003700	Function	DNA-binding transcription factor activity	IEA
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IEA
GO:0005654	Component	Nucleoplasm	IDA
GO:0006355	Process	Regulation of DNA-templated transcription	IEA
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA
GO:0007379	Process	Segment specification	IEA
GO:0007389	Process	Pattern specification process	IEA
GO:0008045	Process	Motor neuron axon guidance	IEA
GO:0009952	Process	Anterior/posterior pattern specification	IEA
GO:0009953	Process	Dorsal/ventral pattern formation	IEA
GO:0021568	Process	Rhombomere 2 development	IEA
GO:0021569	Process	Rhombomere 3 development	IEA
GO:0021658	Process	Rhombomere 3 morphogenesis	IEA
GO:0030182	Process	Neuron differentiation	IEA
GO:0035284	Process	Brain segmentation	IEA
GO:0042474	Process	Middle ear morphogenesis	IEA
GO:0043565	Function	Sequence-specific DNA binding	IEA
GO:0045165	Process	Cell fate commitment	IEA
GO:0045665	Process	Negative regulation of neuron differentiation	IEA
GO:0045668	Process	Negative regulation of osteoblast differentiation	IEA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IEA
GO:0048703	Process	Embryonic viscerocranium morphogenesis	IEA
GO:0048704	Process	Embryonic skeletal system morphogenesis	IEA
GO:0048706	Process	Embryonic skeletal system development	IEA
GO:0060037	Process	Pharyngeal system development	IEA
GO:0061061	Process	Muscle structure development	IEA
GO:0071300	Process	Cellular response to retinoic acid	IEA
GO:1990837	Function	Sequence-specific double-stranded DNA binding	IDA	28473536

Other IDs

• MIM: 604685
• HGNC: 5103
• e!Ensembl: ENSG00000105996

Protein

• UniProt ID: O43364
• Protein name: Homeobox protein Hox-A2 (Homeobox protein Hox-1K)
• Protein function: Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00046	Homeodomain	144 → 200	Homeodomain	Domain

• Sequence:

  MNYEFEREIGFINSQPSLAECLTSFPPVADTFQSSSIKTSTLSHSTLIPPPFEQTIPSLN
  PGSHPRHGAGGRPKPSPAGSRGSPVPAGALQPPEYPWMKEKKAAKKTALLPAAAAAATAA
  ATGPACLSHKESLEIADGSGGGSRRLRTAYTNTQLLELEKEFHFNKYLCRPRRVEIAALL
  DLTERQVKVWFQNRRMKHKRQTQCKENQNSEGKCKSLEDSEKVEEDEEEKTLFEQALSVS
  GALLEREGYTFQQNALSQQQAPNGHNGDSQSFPVSPLTSNEKNLKHFQHQSPTVPNCLST
  MGQNCGAGLNNDSPEALEVPSLQDFSVFSTDSCLQLSDAVSPSLPGSLDSPVDISADSLD
  FFTDTLTTIDLQHLNY

• Sequence length: 376

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
Bilateral microtia-deafness-cleft palate syndrome	Pathogenic	rs2128035211, rs119489104	RCV001771818 RCV000005738	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
HOXA2-related disorder	Pathogenic	rs2534513217	RCV003397745	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
MICROTIA WITH OR WITHOUT HEARING IMPAIRMENT	Pathogenic	rs398122360	RCV000074433	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
MICROTIA WITHOUT HEARING IMPAIRMENT	Pathogenic	rs1554334301	RCV000625727	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
BILATERAL MICROTIA WITH DEAFNESS AND CLEFT PALATE SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL SMALL EARS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEARING IMPAIRMENT	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MICROTIA	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MICROTIA, HEARING IMPAIRMENT, AND CLEFT PALATE	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MICROTIA-ANOTIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
STOMACH NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Attention deficit hyperactivity disorder	Attention Deficit Hyperactivity Disorder	HPO_DG			★☆☆☆☆ Found in Text Mining only
Bilateral microtia-deafness-cleft palate syndrome	Bilateral Microtia-Deafness-Cleft Palate Syndrome	Orphanet			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Carcinoma Renal Cell	Renal cell carcinoma	Pubtator	32444962	Associate	★☆☆☆☆ Found in Text Mining only
Cholangiocarcinoma	Cholangiocarcinoma	Pubtator	21876633	Associate	★☆☆☆☆ Found in Text Mining only
Clubfoot	Clubfoot	Pubtator	19938081	Associate	★☆☆☆☆ Found in Text Mining only
Colitis Ulcerative	Ulcerative colitis	Pubtator	32908909	Associate	★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	31165042		★☆☆☆☆ Found in Text Mining only
Congenital absence of external ear	Anotia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital Microtia	Congenital microtia	Pubtator	23775976	Associate	★☆☆☆☆ Found in Text Mining only
Congenital small ears	Microtia	BEFREE	18394579, 20542577, 23775976, 27503514, 28109504		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital small ears	Microtia	ORPHANET_DG	23775976		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital small ears	Microtia	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cystic Fibrosis	Cystic Fibrosis	BEFREE	8268652		★☆☆☆☆ Found in Text Mining only
Esophageal Squamous Cell Carcinoma	Esophageal squamous cell carcinoma	Pubtator	39596630	Associate	★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	Pubtator	32436804	Associate	★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	Pubtator	35349479	Stimulate	★☆☆☆☆ Found in Text Mining only
Hearing Loss	Hearing loss	Pubtator	23775976	Associate	★☆☆☆☆ Found in Text Mining only
Hearing Loss, Mixed Conductive-Sensorineural	Hearing Loss	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hereditary Diffuse Gastric Cancer	Gastric Cancer	CTD_human_DG	17786296		★☆☆☆☆ Found in Text Mining only
Holoprosencephaly	Holoprosencephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Idiopathic Pulmonary Fibrosis	Pulmonary Fibrosis	BEFREE	31241180		★☆☆☆☆ Found in Text Mining only
Leukemia Myeloid Acute	Myeloid leukemia	Pubtator	31426381	Stimulate	★☆☆☆☆ Found in Text Mining only
Leukemia, Myelocytic, Acute	Leukemia	BEFREE	31426381		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of stomach	Stomach Neoplasms	CTD_human_DG	17786296		★☆☆☆☆ Found in Text Mining only
MICROTIA WITH OR WITHOUT HEARING IMPAIRMENT	MICROTIA WITH OR WITHOUT HEARING IMPAIRMENT	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
MICROTIA WITHOUT HEARING IMPAIRMENT	MICROTIA WITHOUT HEARING IMPAIRMENT	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Microtia, Hearing Impairment, And Cleft Palate	Microtia, Hearing Impairment, And Cleft Palate	UNIPROT_DG	18394579, 23775976		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Microtia, Hearing Impairment, And Cleft Palate	Microtia, Hearing Impairment, And Cleft Palate	ORPHANET_DG	18394579		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Microtia, Hearing Impairment, And Cleft Palate	Microtia, Hearing Impairment, And Cleft Palate	CTD_human_DG	24239177		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Microtia, Hearing Impairment, And Cleft Palate	Microtia, Hearing Impairment, And Cleft Palate	GENOMICS_ENGLAND_DG	27503514, 9367425		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Microtia, Hearing Impairment, And Cleft Palate	Microtia, Hearing Impairment, And Cleft Palate	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nasopharyngeal carcinoma	Nasopharyngeal Carcinoma	BEFREE	24243817		★☆☆☆☆ Found in Text Mining only
Nasopharyngeal Carcinoma	Nasopharyngeal carcinoma	Pubtator	24243817	Associate	★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	17786296, 24243817		★☆☆☆☆ Found in Text Mining only
Orofacial Cleft 1	Orofacial cleft	Pubtator	28603561	Associate	★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	30033361, 35372588, 37143720	Associate	★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma	Carcinoma	BEFREE	17294802, 23172663, 31241180		★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach Neoplasms	CTD_human_DG	17786296		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uranostaphyloschisis	Uranostaphyloschisis	BEFREE	27503514		★☆☆☆☆ Found in Text Mining only