PAX6 - dismech genes

Normal function · from ai-gene-review (P26367, commit 79fe13b38970) · AI-generated, not KB evidence

PAX6 is a paired-box/homeobox sequence-specific DNA-binding transcription factor that acts as a master regulator of development of the eye, central nervous system (forebrain, cerebral cortex, spinal cord), olfactory structures, and pancreatic endocrine cells. The protein contains two DNA-binding modules, an N-terminal bipartite paired domain (with PAI and RED subdomains) and a C-terminal paired-type homeodomain, together with a proline/serine/threonine-rich (PST) C-terminal transactivation domain. PAX6 binds promoter and enhancer cis-regulatory elements of numerous developmental target genes and can act as either a transcriptional activator or repressor in a context-dependent manner. It operates in the nucleus on chromatin and cooperates with partners such as SOX2, MAF/MAFB and the TGF-beta/SMAD pathway. In the endocrine pancreas it controls genes for alpha-cell (glucagon) and beta-cell differentiation and function, contributing to glucose homeostasis. Heterozygous loss-of-function variants cause aniridia and a broad spectrum of anterior and posterior eye malformations, and can be accompanied by glucose intolerance, reflecting the gene's dosage sensitivity and pleiotropy.

PAX6 is a sequence-specific RNA polymerase II DNA-binding transcription factor that binds cis-regulatory (promoter/enhancer) elements of developmental and endocrine target genes via its bipartite paired domain and paired-type homeodomain, acting as a context-dependent activator or repressor.

molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific · directly involved in: regulation of transcription by RNA polymerase II · locations: chromatin; nucleoplasm

PAX6 binds RNA polymerase II cis-regulatory regions in a sequence-specific manner and activates target genes (e.g. miR-135b, glucagon-pathway genes), positively regulating transcription during neural and pancreatic-endocrine programs.

molecular function: RNA polymerase II cis-regulatory region sequence-specific DNA binding · directly involved in: positive regulation of transcription by RNA polymerase II · locations: chromatin

As part of its transcriptional mechanism, PAX6 binds transcriptional cofactors and signaling partners, including R-SMAD/co-SMAD proteins (linking it to TGF-beta signaling) and histone acetyltransferase coactivators, to modulate target-gene output.

molecular function: transcription coregulator binding · directly involved in: regulation of transcription by RNA polymerase II · locations: nucleus

In the knowledge base · computed from kb/ at build time

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

Disorder	Relationship	Where the gene appears
Aniridia	causative	mechanism: PAX6 Haploinsufficiency; Reduced PAX6 Expression after Downstream Regulatory Deletion subtype: Aniridia 1; Aniridia 2; WAGR scoped to subtype: Aniridia 1, Aniridia 2
Congenital Glaucoma	causative germline	mechanism: Neural Crest-Derived Periocular Mesenchyme Maldevelopment subtype: ASD Congenital Glaucoma scoped to subtype: ASD Congenital Glaucoma
Isolated Anophthalmia-Microphthalmia Syndrome	causative	mechanism: Eye Field Transcription Factor Network Dosage Loss
Microphthalmia with Coloboma	untyped Causal dominant haploinsufficiency	mechanism: Disrupted optic-cup and globe morphogenesis subtype: PAX6-MAC scoped to subtype: PAX6-MAC
WAGR Syndrome	no genetic record	mechanism: PAX6 haploinsufficiency and ocular maldevelopment

ClinGen gene–disease validity · snapshot 2026-10-03 · matched to entries by MONDO

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

ClinGen disease	MOI	Classification	dismech entry
PAX6-related ocular dysgenesis MONDO:0800183	AD	Definitive 2022-06-02	no dismech entry

Mechanism modules · computed from kb/

anterior_segment_dysgenesis via Aniridia, Congenital Glaucoma
ocular_morphogenesis_failure via Microphthalmia with Coloboma