HMX2
protein-codingH6 family homeobox 2, the group of NKL subclass homeoboxes and pseudogenes
Gene summary
The protein encoded by this gene is a member of the NKL homeobox family of transcription factors. Members in this family are of ancient origin and play an important role in organ development during embryogenesis. A related mouse protein plays a role in patterning of inner ear structures. In humans, variations in a region containing this gene have been associated with inner ear malformations, vestibular dysfunction, and hearing loss. [provided by RefSeq, Aug 2012]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~2.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to HMX2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005519.2. 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 | 3 | 3 | ||||
| missense | 44 | 1 | 45 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 45 | 3 | 1 | 49 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005510.1 | 2 | MANE Select | |
| Ensembl | ENSP00000341108.3 | 2 | MANE Select | |
| Ensembl | ENSP00000676537.1 | 2 | Standard | |
| Ensembl | ENSP00000807907.1 | 2 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| hmx2 | Danio rerio | Structure: otolith Quality: fused with abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- regulation of transcription by RNA polymerase II
- brain development
- positive regulation of cell population proliferation
- cell differentiation
- inner ear morphogenesis
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- sequence-specific DNA binding
Cellular Component
- nucleus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000339992
- Coding exons
- 2
- Length
- 2551
- Individuals with no LoFs
- 125495
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 23
- Defined
- 125518
- p
- 0.0000916
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0851 | 156 | 153 | 1.02 | 0.00000696 | 1715 |
| Missense (PolyPhen) | 52 | 58.184 | 0.89372 | 634 | ||
| Synonymous | -1.75 | 93 | 73.9 | 1.26 | 0.00000350 | 580 |
| Loss of Function | 0.356 | 7 | 8.09 | 0.865 | 3.47e-7 | 95 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00014 | 0.00012 | rare |
| Latino/Admixed American | 0.00030 | 0.00029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000083 | 0.000079 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcription factor involved in specification of neuronal cell types and which is required for inner ear and hypothalamus development. {ECO:0000250}.;
Recessive Scores
- pRec
- 0.108
Intolerance Scores
- LoFtool
- 0.219
- RVIS EVS
- 0.17
- RVIS percentile EVS
- 65.56
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.566
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |