HOXA2

homeobox A2, the group of HOXL subclass homeoboxes

Basic information

Region (hg38): 7:27100353-27102686

Previous symbols: [ "HOX1K" ]

Links

ENSG00000105996 ∙ NCBI:3199 ∙ OMIM:604685 ∙ HGNC:5103 ∙ Uniprot:O43364 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• bilateral microtia-deafness-cleft palate syndrome (Strong), mode of inheritance: AD
• bilateral microtia-deafness-cleft palate syndrome (Limited), mode of inheritance: AR
• bilateral microtia-deafness-cleft palate syndrome (Moderate), mode of inheritance: Semidominant
• microtia (Supportive), mode of inheritance: AD
• bilateral microtia-deafness-cleft palate syndrome (Supportive), mode of inheritance: AD
• bilateral microtia-deafness-cleft palate syndrome (Moderate), mode of inheritance: AD
• bilateral microtia-deafness-cleft palate syndrome (Limited), mode of inheritance: AR
• bilateral microtia-deafness-cleft palate syndrome (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Microtia, hearing impairment, and cleft palate	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal	18394579

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HOXA2 gene.

• Bilateral microtia-deafness-cleft palate syndrome (33 variants)
• Inborn genetic diseases (17 variants)
• not provided (7 variants)
• HOXA2-related condition (3 variants)
• Human HOXA1 syndromes (1 variants)
• not specified (1 variants)
• Bosley-Salih-Alorainy syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HOXA2 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			7			7
missense			27			27
nonsense			1			1
start loss						0
frameshift	1					1
inframe indel			2			2
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			13	2	3	18
Total	1	0	50	2	3

Variants in HOXA2

This is a list of pathogenic ClinVar variants found in the HOXA2 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-27100369-A-G		Bilateral microtia-deafness-cleft palate syndrome	Uncertain significance (Jan 12, 2018)
7-27100388-A-G		Bilateral microtia-deafness-cleft palate syndrome	Uncertain significance (Jan 13, 2018)
7-27100410-A-G		Bilateral microtia-deafness-cleft palate syndrome	Benign (Jan 13, 2018)
7-27100512-G-T		Bilateral microtia-deafness-cleft palate syndrome	Uncertain significance (Jan 13, 2018)
7-27100516-T-A		Bilateral microtia-deafness-cleft palate syndrome	Uncertain significance (Jan 12, 2018)
7-27100517-A-G		Bilateral microtia-deafness-cleft palate syndrome	Uncertain significance (Jan 22, 2018)
7-27100533-C-G		Bilateral microtia-deafness-cleft palate syndrome	Uncertain significance (Jan 12, 2018)
7-27100560-T-C		Bilateral microtia-deafness-cleft palate syndrome	Uncertain significance (Jan 13, 2018)
7-27100618-G-A		Bilateral microtia-deafness-cleft palate syndrome • Bosley-Salih-Alorainy syndrome • Human HOXA1 syndromes	Likely benign (Jun 14, 2016)
7-27100661-A-G		Bilateral microtia-deafness-cleft palate syndrome	Uncertain significance (Jan 13, 2018)
7-27100696-T-C		Bilateral microtia-deafness-cleft palate syndrome	Uncertain significance (Jan 13, 2018)
7-27100770-T-C		Inborn genetic diseases	Uncertain significance (Jun 24, 2022)
7-27100792-T-C		Bilateral microtia-deafness-cleft palate syndrome	Uncertain significance (Jan 12, 2018)
7-27100848-A-T		HOXA2-related disorder	Uncertain significance (Sep 25, 2023)
7-27100851-G-C		Bilateral microtia-deafness-cleft palate syndrome	Uncertain significance (Mar 02, 2018)
7-27100851-G-T		HOXA2-related disorder	Likely benign (Jan 31, 2024)
7-27100852-C-T		Bilateral microtia-deafness-cleft palate syndrome	Uncertain significance (Jan 13, 2018)
7-27100869-T-C		Inborn genetic diseases	Uncertain significance (Dec 02, 2021)
7-27100878-C-T		Bilateral microtia-deafness-cleft palate syndrome	Uncertain significance (Apr 27, 2017)
7-27100887-C-T		Bilateral microtia-deafness-cleft palate syndrome	Uncertain significance (Jan 13, 2018)
7-27100903-C-T		HOXA2-related disorder	Likely benign (Dec 26, 2019)
7-27100905-C-G		Inborn genetic diseases	Uncertain significance (Apr 25, 2022)
7-27100978-A-C		HOXA2-related disorder	Likely benign (Jul 01, 2020)
7-27100985-G-A		Inborn genetic diseases	Uncertain significance (Dec 15, 2023)
7-27100992-G-A		HOXA2-related disorder	Likely benign (Feb 03, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HOXA2	protein_coding	protein_coding	ENST00000222718	2	2710

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.199	0.792	125737	0	11	125748	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.414	175	191	0.916	0.00000974	2445
Missense in Polyphen		51	62.143	0.82068		830
Synonymous	0.0232	84	84.3	0.997	0.00000479	767
Loss of Function	2.25	3	11.1	0.271	4.90e-7	141

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000173	0.000173
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000440	0.0000439
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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.
• Disease: DISEASE: Microtia, hearing impairment, and cleft palate (MHICP) [MIM:612290]: A disease characterized by microtia, mixed symmetric severe to profound hearing impairment, and partial cleft palate. Microtia is a congenital deformity of the outer ear that is small and abnormally shaped. In classic microtia, the pinna is essentially absent, except for a vertical sausage-shaped skin remnant. The superior aspect of this sausage-shaped skin remnant consists of underlying unorganized cartilage, and the inferior aspect of this remnant consists of a relatively well-formed lobule. Syndromic forms of microtia occur in conjunction with other abnormalities including cleft palate, a congenital fissure of the soft and/or hard palate due to faulty fusion. {ECO:0000269|PubMed:18394579}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Microtia with or without hearing impairment (MCRT) [MIM:612290]: Microtia is a congenital deformity of the outer ear that is small and abnormally shaped. In classic microtia, the pinna is essentially absent, except for a vertical sausage-shaped skin remnant. The superior aspect of this sausage-shaped skin remnant consists of underlying unorganized cartilage, and the inferior aspect of this remnant consists of a relatively well- formed lobule. {ECO:0000269|PubMed:23775976}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Activation of anterior HOX genes in hindbrain development during early embryogenesis;Developmental Biology;Regulation of expression of SLITs and ROBOs;Signaling by ROBO receptors;Axon guidance (Consensus)

Recessive Scores

• pRec: 0.139

Intolerance Scores

• loftool: 0.138
• rvis_EVS: -0.34
• rvis_percentile_EVS: 30.07

Haploinsufficiency Scores

• pHI: 0.424
• hipred: Y
• hipred_score: 0.525
• ghis: 0.545

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.700

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hoxa2
• Phenotype: skeleton 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; 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; embryo phenotype; cellular phenotype; craniofacial phenotype; muscle phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;cell fate determination;osteoblast development;segment specification;motor neuron axon guidance;anterior/posterior pattern specification;dorsal/ventral pattern formation;rhombomere 2 development;rhombomere 3 morphogenesis;brain segmentation;middle ear morphogenesis;negative regulation of neuron differentiation;negative regulation of osteoblast differentiation;positive regulation of transcription by RNA polymerase II;embryonic viscerocranium morphogenesis;embryonic skeletal system morphogenesis;cellular response to retinoic acid
• Cellular component: nucleus;intracellular membrane-bounded organelle
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription repressor activity, RNA polymerase II-specific;DNA-binding transcription factor activity