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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
RAX
retina and anterior neural fold homeobox
Chromosome 18 Β· 18q21.32
NCBI Gene: 30062Ensembl: ENSG00000134438.10HGNC: HGNC:18662UniProt: Q9Y2V3
20PubMed Papers
21Diseases
0Drugs
11Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
positive regulation of transcription by RNA polymerase IIRNA polymerase II cis-regulatory region sequence-specific DNA bindingDNA-binding transcription activator activity, RNA polymerase II-specificnucleusIsolated anophthalmia - microphthalmiamicrophthalmiaretinopathyEpiretinal membrane
✦AI Summary

RAX is a paired-type homeodomain transcription factor essential for vertebrate eye development and anterior central nervous system patterning 1. The gene encodes a DNA-binding transcription activator that regulates retinal cell specification and proliferation by binding to photoreceptor-specific regulatory elements 2. RAX expression is conserved across metazoans, with evolutionary evidence suggesting its origin in the common ancestor of Cnidaria and Bilateria, followed by segmental duplication in early jawed vertebrates creating RAX and RAX2 paralogs 3. Beyond ocular development, RAX plays crucial roles in hypothalamic and pituitary patterning, controlling expression of Sonic hedgehog signaling 1. Mutations in RAX cause syndromic microphthalmia 16, characterized by congenital anophthalmia, cleft lip/palate, craniofacial hypoplasia, and endocrine dysfunction including hypopituitarism 4. RAX mutations specifically impair retinal differentiation rather than lens induction, distinguishing its role from other ocular developmental genes 5. Both autosomal recessive and compound heterozygous inheritance patterns have been documented in human patients 2. These findings establish RAX as a critical developmental regulator with broad implications for understanding congenital eye malformations and hypothalamic-pituitary axis development.

Sources cited
1
RAX encodes a paired-type homeodomain transcription factor important for eye, hypothalamus, and pituitary development; controls Shh expression
PMID: 32930382
2
First report of human RAX mutations causing anophthalmia/microphthalmia; mutations affect DNA-binding homeodomain; autosomal recessive inheritance
PMID: 14662654
3
RAX origin dates to Cnidaria-Bilateria ancestor; vertebrate segmental duplication created RAX and RAX2 paralogs
PMID: 32144893
4
RAX mutations cause syndromic microphthalmia with anophthalmia, cleft palate, hypopituitarism, and diabetes insipidus
PMID: 40321348
5
RAX has retinal expression and causes anophthalmia/microphthalmia through failure of retinal differentiation
PMID: 18039390
Disease Associationsβ“˜21
Isolated anophthalmia - microphthalmiaOpen Targets
0.80Strong
microphthalmiaOpen Targets
0.67Moderate
retinopathyOpen Targets
0.45Moderate
Epiretinal membraneOpen Targets
0.41Moderate
microphthalmia, isolated, with colobomaOpen Targets
0.39Weak
nanophthalmiaOpen Targets
0.38Weak
isolated microphthalmiaOpen Targets
0.37Weak
response to COVID-19 vaccineOpen Targets
0.32Weak
joint diseaseOpen Targets
0.32Weak
Abnormal pupillary functionOpen Targets
0.20Weak
genetic disorderOpen Targets
0.19Weak
anophthalmia-microphthalmia syndromeOpen Targets
0.17Weak
microphthalmia, isolated, with coloboma 10Open Targets
0.07Suggestive
Microphthalmia - ankyloblepharon - intellectual disabilityOpen Targets
0.07Suggestive
microphthalmia, isolated, with coloboma 5Open Targets
0.07Suggestive
microphthalmia, isolated, with coloboma 7Open Targets
0.06Suggestive
early-onset non-syndromic cataractOpen Targets
0.06Suggestive
Cataract-microcornea syndromeOpen Targets
0.06Suggestive
isolated microphthalmia 7Open Targets
0.06Suggestive
nanophthalmos 2Open Targets
0.06Suggestive
Microphthalmia, syndromic 16UniProt
Pathogenic Variants11
NM_013435.3(RAX):c.543+3A>GLikely pathogenic
Isolated microphthalmia 3
β˜…β˜†β˜†β˜†2025
NM_013435.3(RAX):c.50_53dup (p.Gly19fs)Likely pathogenic
Isolated microphthalmia 3
β˜…β˜†β˜†β˜†2024β†’ Residue 19
NM_013435.3(RAX):c.499G>T (p.Glu167Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 167
NM_013435.3(RAX):c.106G>T (p.Glu36Ter)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2020β†’ Residue 36
NM_013435.3(RAX):c.262_263delinsA (p.Ala88fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2017β†’ Residue 88
NM_013435.3(RAX):c.560G>A (p.Arg187Gln)Pathogenic
Isolated microphthalmia 3
β˜†β˜†β˜†β˜†2022β†’ Residue 187
NM_013435.3(RAX):c.266del (p.Pro89fs)Pathogenic
Isolated microphthalmia 3
β˜†β˜†β˜†β˜†2022β†’ Residue 89
NM_013435.3(RAX):c.664del (p.Ser222fs)Pathogenic
Isolated microphthalmia 3
β˜†β˜†β˜†β˜†2008β†’ Residue 222
NM_013435.3(RAX):c.909C>G (p.Tyr303Ter)Pathogenic
Isolated microphthalmia 3
β˜†β˜†β˜†β˜†2008β†’ Residue 303
NM_013435.3(RAX):c.575G>A (p.Arg192Gln)Pathogenic
Isolated microphthalmia 3
β˜†β˜†β˜†β˜†2004β†’ Residue 192
NM_013435.3(RAX):c.439C>T (p.Gln147Ter)Pathogenic
Isolated microphthalmia 3
β˜†β˜†β˜†β˜†2004β†’ Residue 147
View on ClinVar β†—
Related Genes
IMPG1Shared pathway100%ROM1Shared pathway100%PRR4Shared pathway100%AIPL1Shared pathway100%NYXShared pathway100%IMPG2Shared pathway100%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
7%
Heart
0%
Ovary
0%
Liver
0%
Lung
0%
Gene Interaction Network
Click a node to explore
RAXIMPG1ROM1PRR4AIPL1NYXIMPG2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q9Y2V3
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.20LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.74 [0.47–1.20]
RankingsWhere RAX stands among ~20K protein-coding genes
  • #14,238of 20,598
    Most Researched20
  • #2,804of 5,498
    Most Pathogenic Variants11
  • #12,579of 17,882
    Most Constrained (LOEUF)1.20
Genes detectedRAX
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Atezolizumab Plus Chemotherapy for First-Line Treatment of Nonsquamous NSCLC: Results From the Randomized Phase 3 IMpower132 Trial.
PMID: 33333328
J Thorac Oncol Β· 2021
1.00
2
Conserved roles of
PMID: 32930382
Int J Dev Biol Β· 2021
0.90
3
Origin and evolution of the Rax homeobox gene by comprehensive evolutionary analysis.
PMID: 32144893
FEBS Open Bio Β· 2020
0.80
4
Mutations in the human RAX homeobox gene in a patient with anophthalmia and sclerocornea.
PMID: 14662654
Hum Mol Genet Β· 2004
0.70
5
Prkra dimer senses double-stranded RNAs to dictate global translation efficiency.
PMID: 40280134
Mol Cell Β· 2025
0.60