IRX6

Chr 16

iroquois homeobox 6

Also known as: IRX-3, IRX7, IRXB3

NCBI Gene: 79190 ENSG00000159387 UniProt: P78412

Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific; DNA-binding transcription repressor activity, RNA polymerase II-specific; and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in cell development; neuron differentiation; and regulation of DNA-templated transcription. Predicted to act upstream of or within detection of visible light; negative regulation of DNA-templated transcription; and retina morphogenesis in camera-type eye. Predicted to be located in chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

Active trials

Pathogenic / LP

125

ClinVar variants

Pubs (1 yr)

-1.9

Missense Z

1.33

LOEUF

Clinical Summary— IRX6

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

19 Pathogenic / Likely Pathogenic· 105 VUS of 125 total submissions

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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.

1.33LOEUF

pLI 0.000

Z-score 0.39

OE 0.91 (0.63–1.33)

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.

-1.85Z-score

OE missense 1.32 (1.21–1.45)

345 obs / 260.9 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.0.91 (0.63–1.33)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.32 (1.21–1.45)

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.1.23

0≤1.21.6

LoF obs/exp: 19 / 20.9Missense obs/exp: 345 / 260.9Syn Z: -1.91