HOXA11
protein-codinghomeobox A11, 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. This gene is involved in the regulation of uterine development and is required for female fertility. Mutations in this gene can cause radio-ulnar synostosis with amegakaryocytic thrombocytopenia. [provided by RefSeq, Jul 2008]
- HOX1I
- HOX1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~4.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0024558
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0011555
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0024558
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0024558
Submitter: ClinGen
HOXA11 was first reported in relation to autosomal dominant radioulnar synostosis with amegakaryocytic thrombocytopenia 1 (RUSAT 1) in 2000 (Thompson AA, et al; PMID: 11101832). RUSAT is characterized by thrombocytopenia that progresses to pancytopenia, in association with congenital proximal fusion of the radius and ulna that results in extremely limited pronation and supination of the forearm (summary by Niihori et al., 2015; PMID: 26581901). One frameshift variant (c.872del) has been reported in two probands in one publication (PMID: 11101832), segregating in four additional affected family members. This gene-disease association is supported by its expression during limb development and a mouse model with skeletal malformations in the limbs (PMID: 7902826), as well as its expression and function in early hematopoietic development (PMID: 16765069). In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This gene-disease pair was previously evaluated by the HT GCEP on April 28, 2021. It was reevaluated on September 4, 2024. As a result of this reevaluation no new evidence was identified and the classification remained Limited (SOP Version 10).
Inheritance Pattern: AD
Disease ID:MONDO:0024558
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0024558
Submitter: G2P
Clinical Genomic Database (CGD)
Manifestation: Hematologic; Musculoskeletal
Intervention: Hematologic
Rationale: Individuals can have symptomatic thrombocytopenia and bone marrow failure manifesting in the neonatal period, requiring early bone marrow/umbilical cord stem cell transplantation
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to HOXA11 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005523.6. 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 | 1 | 23 | 24 | |||
| missense | 2 | 66 | 6 | 3 | 77 | |
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | 2 | |||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 1 | 2 | 68 | 29 | 3 | 103 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005514.1 | 2 | MANE Select | |
| Ensembl | ENSP00000006015.3 | 2 | MANE Select | |
| Ensembl | ENSP00000448962.1 | 3 | Standard | |
| Ensembl | ENSP00000801216.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Transcriptional misregulation in cancer - Homo sapiens (human)
Biological Process
- skeletal system development
- metanephros development
- branching involved in ureteric bud morphogenesis
- organ induction
- regulation of transcription by RNA polymerase II
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- sequence-specific DNA binding
Cellular Component
- nucleoplasm
- transcription factor complex
- protein-containing complex
- protein-DNA complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000006015
- Coding exons
- 2
- Length
- 3714
- Individuals with no LoFs
- 124889
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 124890
- p
- 0.00000400
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.668 | 144 | 168 | 0.855 | 0.00000846 | 2012 |
| Missense (PolyPhen) | 41 | 69.611 | 0.58899 | 829 | ||
| Synonymous | -2.06 | 96 | 73.5 | 1.31 | 0.00000368 | 648 |
| Loss of Function | 2.79 | 0 | 9.08 | 0.00 | 4.44e-7 | 110 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000089 | 0.0000089 | 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: Radioulnar synostosis with amegakaryocytic thrombocytopenia 1 (RUSAT1) [MIM:605432]: The syndrome consists of an unusual association of bone marrow failure and skeletal defects. Patients have the same skeletal defects, the proximal fusion of the radius and ulna, resulting in extremely limited pronation and supination of the forearm. Some patients have also symptomatic thrombocytopenia, with bruising and bleeding problems since birth, necessitating correction by bone marrow or umbilical- cord stem-cell transplantation. {ECO:0000269|PubMed:11101832}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.230
Intolerance Scores
- LoFtool
- 0.216
- RVIS EVS
- -0.36
- RVIS percentile EVS
- 28.63
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.996
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |