HOXD12
protein-codinghomeobox D12, the group of HOXL subclass homeoboxes
Gene summary
This gene belongs to the homeobox family of genes. The homeobox genes encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms. Mammals possess four similar homeobox gene clusters, HOXA, HOXB, HOXC and HOXD, located on different chromosomes, consisting of 9 to 11 genes arranged in tandem. This gene is one of several homeobox HOXD genes located in a cluster on chromosome 2. Deletions that remove the entire HOXD gene cluster or the 5' end of this cluster have been associated with severe limb and genital abnormalities. The exact role of this gene has not been determined. [provided by RefSeq, Jul 2008]
- HOX4H
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~2.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0007342
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to HOXD12 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_021193.4. 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 | 0 | |||||
| missense | 64 | 3 | 67 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 64 | 4 | 0 | 68 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_067016.3 | 2 | MANE Select | |
| Ensembl | ENSP00000385586.2 | 2 | MANE Select | |
| Ensembl | ENSP00000385132.2 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- skeletal system development
- regulation of transcription by RNA polymerase II
- pattern specification process
- embryonic digit morphogenesis
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- protein binding
- sequence-specific DNA binding
Cellular Component
- nucleus
- transcription factor complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000406506
- Coding exons
- 2
- Length
- 1951
- Individuals with no LoFs
- 124564
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 59
- Defined
- 124623
- p
- 0.000237
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -1.34 | 202 | 155 | 1.30 | 0.00000713 | 1675 |
| Missense (PolyPhen) | 78 | 54.902 | 1.4207 | 674 | ||
| Synonymous | -0.918 | 81 | 71.1 | 1.14 | 0.00000335 | 587 |
| Loss of Function | 0.538 | 6 | 7.60 | 0.789 | 3.24e-7 | 87 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00023 | 0.00019 | rare |
| Latino/Admixed American | 0.00013 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00032 | 0.00028 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00040 | 0.00035 | rare |
| South Asian | 0.00028 | 0.00023 | rare |
| Other | 0.00019 | 0.00017 | rare |
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.;
Recessive Scores
- pRec
- 0.193
Intolerance Scores
- LoFtool
- 0.432
- RVIS EVS
- 0.4
- RVIS percentile EVS
- 76.15
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.750
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |