IRX1

Chr 5

iroquois homeobox 1

Also known as: IRX-5, IRXA1

NCBI Gene: 79192ENSG00000170549UniProt: P78414

This gene encodes a member of the Iroquois homeobox protein family. Homeobox genes in this family are involved in pattern formation in the embryo. The gene product has been identified as a tumor suppressor in gastric (PMID: 21602894, 20440264) and head and neck cancers (PMID: 18559491). A pseudogene of this gene is located on chromosome 13. [provided by RefSeq, Dec 2011]

100
ClinVar variants
79
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— IRX1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
79 Pathogenic / Likely Pathogenic· 16 VUS of 100 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.
1.07LOEUF
pLI 0.000
Z-score 1.40
OE 0.57 (0.32–1.07)
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.
-0.59Z-score
OE missense 1.11 (1.00–1.23)
266 obs / 240.2 exp
Tolerant

Tolerant to missense variation

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.0.57 (0.32–1.07)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.11 (1.00–1.23)
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.1.43
0≤1.21.6
LoF obs/exp: 7 / 12.3Missense obs/exp: 266 / 240.2Syn Z: -3.62

ClinVar Variant Classifications

100 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic77
Likely Pathogenic2
VUS16
Likely Benign2
Benign3
77
Pathogenic
2
Likely Pathogenic
16
VUS
2
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
77
0
77
Likely Pathogenic
0
0
2
0
2
VUS
0
13
3
0
16
Likely Benign
0
0
0
2
2
Benign
0
1
0
2
3
Total014824100

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

View in ClinVar →

Protein Context — Lollipop Plot

IRX1 · 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
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Landscape of driver mutations and their clinical effects on Down syndrome-related myeloid neoplasms.
Sato T et al.·Blood
2024
IRX1 is a novel gene, overexpressed in high-grade IDH-mutant astrocytomas.
Sugur HS et al.·Pathol Res Pract
2023
Human Genetics of Hypoplastic Left Heart Syndrome.
Pfitzer C et al.·Adv Exp Med Biol
2024
[Expression of IRX1 in cervical cancer and its correlation with clinical stage of cervical cancer].
He Y et al.·Zhonghua Yi Xue Za Zhi
2018
Clinical significance of Iroquois Homeobox Gene - IRX1 in human glioma.
Zhang P et al.·Mol Med Rep
2018
HOXA9/IRX1 expression pattern defines two subgroups of infant MLL-AF4-driven acute lymphoblastic leukemia.
Symeonidou V et al.·Exp Hematol
2021
IRX1 hypomethylation promotes osteosarcoma metastasis via induction of CXCL14/NF-κB signaling.
Lu J et al.·J Clin Invest
2015
Duplication events downstream of IRX1 cause North Carolina macular dystrophy at the MCDR3 locus.
Cipriani V et al.·Sci Rep
2017
Hypermethylation of EBF3 and IRX1 genes in synovial fibroblasts of patients with rheumatoid arthritis.
Park SH et al.·Mol Cells
2013Cohort
HPV status-independent association of alcohol and tobacco exposure or prior radiation therapy with promoter methylation of FUSSEL18, EBF3, IRX1, and SEPT9, but not SLC5A8, in head and neck squamous cell carcinomas.
Bennett KL et al.·Genes Chromosomes Cancer
2010
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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