IRX5
Chr 16ARiroquois homeobox 5
Also known as: HMMS, IRX-2a, IRXB2
IRX5 encodes a transcription factor that establishes cardiac repolarization gradients by repressing potassium channel gene expression, promotes retinal cone bipolar cell differentiation, and regulates craniofacial and gonadal development through control of cell migration. Loss-of-function mutations cause Hamamy syndrome, an autosomal recessive disorder. The gene is highly intolerant to loss-of-function variants, supporting haploinsufficiency as the pathogenic mechanism.
Primary Disease Associations & Inheritance
Moderate evidence — consider for supplementary testing
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
163 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 1 | 3 | 16 | 0 | 20 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 1 | 91 | 5 | 0 | 97 |
Likely Benign | 0 | 3 | 0 | 32 | 35 |
Benign | 0 | 2 | 4 | 2 | 8 |
Conflicting | — | 1 | |||
| Total | 2 | 99 | 26 | 34 | 162 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
IRX5 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools