HOXB6

Chr 17

homeobox B6

Also known as: HOX2, HOX2B, HU-2, Hox-2.2

NCBI Gene: 3216ENSG00000108511UniProt: P17509

This gene is a member of the Antp homeobox family and encodes a protein with a homeobox DNA-binding domain. It is included in a cluster of homeobox B genes located on chromosome 17. The encoded protein functions as a sequence-specific transcription factor that is involved in development, including that of lung and skin, and has been localized to both the nucleus and cytoplasm. Altered expression of this gene or a change in the subcellular localization of its protein is associated with some cases of acute myeloid leukemia and colorectal cancer. [provided by RefSeq, Jul 2008]

0
Active trials
10
Pathogenic / LP
60
ClinVar variants
2
Pubs (1 yr)
0.1
Missense Z
1.26
LOEUF
Clinical Summary— HOXB6
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
10 Pathogenic / Likely Pathogenic· 40 VUS of 60 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
1.26LOEUF
pLI 0.001
Z-score 1.03
OE 0.64 (0.35–1.26)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.14Z-score
OE missense 0.96 (0.83–1.12)
120 obs / 124.4 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.0.64 (0.35–1.26)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.96 (0.83–1.12)
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.1.13
0≤1.21.6
LoF obs/exp: 6 / 9.4Missense obs/exp: 120 / 124.4Syn Z: -0.77

ClinVar Variant Classifications

60 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic1
VUS40
Likely Benign2
Benign8
9
Pathogenic
1
Likely Pathogenic
40
VUS
2
Likely Benign
8
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
9
0
9
Likely Pathogenic
0
0
1
0
1
VUS
0
37
3
0
40
Likely Benign
0
0
0
2
2
Benign
0
0
6
2
8
Total03719460

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

View in ClinVar →

Protein Context — Lollipop Plot

HOXB6 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
HOMEOBOX B6; HOXB6
MIM #142961 · *

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Gene expression analysis in endometriosis: Immunopathology insights, transcription factors and therapeutic targets
Geng R et al.·Front Immunol
2022
HOXB6 down-regulation induced by retinoic acid pathway repression leads to chondrocyte proliferation inhibition and apoptosis in microtia.
Yang R et al.·Genes Dis
2024
HOX gene dysregulation in glioblastoma: a narrative review of current advances
Hekim S et al.·Discov Oncol
2025Review
Immunolocalization of some HOX proteins in immature and mature feline testes.
Topaloğlu U et al.·Anat Histol Embryol
2021
Yin G et al.·Zhejiang Da Xue Xue Bao Yi Xue Ban
2024
Innate differences in the molecular signature of normal inferior & superior human parathyroid glands: potential implications for parathyroid adenoma.
Agarwal S et al.·Mol Cell Biochem
2023
Fate mapping and scRNA sequencing reveal origin and diversity of lymph node stromal precursors.
Lenti E et al.·Immunity
2022
Top 7 full-text resultsSearch PubTator3 ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients