IRX1

Chr 5

iroquois homeobox 1

Also known as: IRX-5, IRXA1

This gene encodes an Iroquois homeobox transcription factor that regulates embryonic pattern formation. Mutations cause autosomal dominant developmental delay, intellectual disability, and multiple congenital anomalies affecting craniofacial features, limbs, and other organ systems. The gene shows low constraint against loss-of-function variants, consistent with the dominant inheritance pattern observed in affected families.

OMIMResearchSummary from RefSeq
DNmechanismLOEUF 1.07
Clinical SummaryIRX1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.07LOEUF
pLI 0.000
Z-score 1.40
OE 0.57 (0.321.07)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.59Z-score
OE missense 1.11 (1.001.23)
266 obs / 240.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.57 (0.321.07)
00.351.4
Missense OE1.11 (1.001.23)
00.61.4
Synonymous OE1.43
01.21.6
LoF obs/exp: 7 / 12.3Missense obs/exp: 266 / 240.2Syn Z: -3.62
DN
0.6649th %ile
GOF
0.4678th %ile
LOF
0.58top 25%

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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