HOXA2
protein-codinghomeobox A2, the group of HOXL subclass homeoboxes
Gene 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 development. This gene is part of the A cluster on chromosome 7 and encodes a DNA-binding transcription factor which may regulate gene expression, morphogenesis, and differentiation. The encoded protein may be involved in the placement of hindbrain segments in the proper location along the anterior-posterior axis during development. [provided by RefSeq, Jul 2008]
- HOX1K
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~2.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0012854
Submitter: Laboratory for Molecular Medicine
This gene-disease relationship has undergone rapid assessment. Classifications are based on preliminary review of gene-disease validity during analysis of genomic sequencing results.
Inheritance Pattern: SD
Disease ID:MONDO:0012854
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0012854
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0012854
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0010920
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0012854
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0012854
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0012854
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0012854
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0012854
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal
Intervention: Audiologic/Otolaryngologic
Rationale: Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to HOXA2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006735.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 6 | 5 | 11 | |||
| missense | 1 | 60 | 5 | 66 | ||
| nonsense | 2 | 1 | 1 | 4 | ||
| start loss | 0 | |||||
| frameshift | 2 | 3 | 1 | 6 | ||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 5 | 4 | 68 | 10 | 0 | 87 |
Highest pathogenic variant AF is 7.43185e-7
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006726.1 | 2 | MANE Select | |
| Ensembl | ENSP00000222718.5 | 2 | MANE Select | |
| Ensembl | ENSP00000801793.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- 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
Biological Process
- negative regulation of transcription by RNA polymerase II
- cell fate determination
- osteoblast development
- segment specification
- motor neuron axon guidance
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
Cellular Component
- nucleus
- intracellular membrane-bounded organelle
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000222718
- Coding exons
- 2
- Length
- 2710
- Individuals with no LoFs
- 125737
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 11
- Defined
- 125748
- p
- 0.0000437
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.414 | 175 | 191 | 0.916 | 0.00000974 | 2445 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00017 | 0.00017 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000044 | 0.000044 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- 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.;
Recessive Scores
- pRec
- 0.139
Intolerance Scores
- LoFtool
- 0.138
- RVIS EVS
- -0.34
- RVIS percentile EVS
- 30.07
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.700
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |