HOXA11

Chr 7AD

homeobox A11

Also known as: HOX1, HOX1I, RUSAT1

NCBI Gene: 3207ENSG00000005073UniProt: P31270

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]

Primary Disease Associations & Inheritance

Radioulnar synostosis with amegakaryocytic thrombocytopenia 1MIM #605432
AD
118
ClinVar variants
34
Pathogenic / LP
0.94
pLI score· haploinsufficient
0
Active trials
Clinical Summary— HOXA11
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Gene-Disease Validity (ClinGen)
radioulnar synostosis with amegakaryocytic thrombocytopenia 1 · ADLimited

Limited evidence — not for standalone diagnostic reporting

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.94). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
34 Pathogenic / Likely Pathogenic· 67 VUS of 118 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.33LOEUF
pLI 0.943
Z-score 2.79
OE 0.00 (0.00–0.33)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.67Z-score
OE missense 0.86 (0.75–0.98)
144 obs / 168.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.33)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.86 (0.75–0.98)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.31
0≤1.21.6
LoF obs/exp: 0 / 9.1Missense obs/exp: 144 / 168.4Syn Z: -2.06

ClinVar Variant Classifications

118 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic29
Likely Pathogenic5
VUS67
Likely Benign11
Benign5
Conflicting1
29
Pathogenic
5
Likely Pathogenic
67
VUS
11
Likely Benign
5
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
28
0
29
Likely Pathogenic
0
2
3
0
5
VUS
1
60
6
0
67
Likely Benign
0
3
2
6
11
Benign
0
2
3
0
5
Conflicting
—1
Total267426118

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

HOXA11 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

HOXA11-related radioulnar synostosis with amegakaryocytic thrombocytopenia

limited
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
HOMEOBOX A11; HOXA11
MIM #142958 · *

Radioulnar synostosis with amegakaryocytic thrombocytopenia 1

MIM #605432

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
HOXA11 antisense long noncoding RNA (HOXA11-AS): A promising lncRNA in human cancers.
Lu CW et al.·Cancer Med
2018Review
Long non-coding RNA HOXA11-AS in human cancer: A meta-analysis.
Li N et al.·Clin Chim Acta
2017Review
Recent advances in unraveling the molecular mechanisms and functions of HOXA11‑AS in human cancers and other diseases (Review).
Wei C et al.·Oncol Rep
2020Review
LncRNA HOXA11-AS intercepts the POU2F2-mediated downregulation of SLC3A2 in osteoarthritis to suppress ferroptosis.
Yu B et al.·Cell Signal
2024
[Micro-RNAs and muscle differentiation].
Naguibneva I et al.·J Soc Biol
2007Review
Transcriptional landscape of pleural mesothelioma patients in relation to NF2 gene mutational status.
Orozco-Castaño C et al.·J Egypt Natl Canc Inst
2025Cohort
[HOX genes and the limb development in the clinical praxis and in the experiment].
Snajdr P et al.·Cas Lek Cesk
2010Review
Clinical Significance and Effect of lncRNA HOXA11-AS in NSCLC: A Study Based on Bioinformatics, In Vitro and in Vivo Verification.
Zhang Y et al.·Sci Rep
2017
HOX cluster-embedded antisense long non-coding RNAs in lung cancer.
Li L et al.·Cancer Lett
2019Review
In silico interaction of HOX cluster-embedded microRNAs and long non-coding RNAs in oral cancer.
Padam KSR et al.·J Oral Pathol Med
2022Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Failure of podocalyxin suppression and HOXA10/HOXA11 activation characterizes endometrial dysfunction in hyperandrogenic PCOS.
Celik N et al.·Mol Cell Endocrinol
2026
HOXA10 and HOXA11 Methylation: Epigenetic Barriers to Endometrial Receptivity in ART.
Kudlay D et al.·Genes (Basel)
2025🔓 Open Access
LncRNA HOXA11-AS promotes the cell proliferation, migration, invasion and inhibits cell apoptosis in esophageal squamous cell carcinoma.
Li W et al.·Sci Rep
2025🔓 Open Access
YY1-induced Long non-coding RNA HOXA11-AS activates oxidative stress and inflammation by epigenetic modification of Nrf2 pathway to promote keloid formation.
Jin J et al.·Redox Rep
2025🔓 Open Access
RETRACTED: Zhou et al. HOXA11-AS1 Promotes PD-L1-Mediated Immune Escape and Metastasis of Hypopharyngeal Carcinoma by Facilitating PTBP1 and FOSL1 Association. Cancers 2022, 14, 3694.
Zhou Z et al.·Cancers (Basel)
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools