Treacher Collins syndrome 2: genes and variants
Treacher Collins syndrome 2 is linked to 2 analyzed proteins (POLR1D and TGM1). 3 DNA variants are known to cause it; 2 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Also known as: Treacher Collins syndrome 1; Treacher-Collins syndrome
Genes linked to Treacher Collins syndrome 2
POLR1D: DNA-directed RNA polymerases I and III subunit RPAC2
2 disease-causing and 2 uncertain variants in POLR1D are linked to Treacher Collins syndrome 2.
TGM1: Protein-glutamine gamma-glutamyltransferase K
It crosslinks structural proteins and lipids during formation of the cornified envelope, creating the mechanically resilient outer skin barrier. Biallelic loss-of-function variants are a major cause of autosomal recessive congenital ichthyosis, particularly lamellar ichthyosis.
1 disease-causing and 0 uncertain variants in TGM1 are linked to Treacher Collins syndrome 2.
Known disease-causing variants in Treacher Collins syndrome 2
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| TGM1 R264Q | 264 | Disease-causing (★★) | |
| POLR1D L55V | 55 | Disease-causing | |
| POLR1D L51R | 51 | Disease-causing |
Same protein, different disease
- Autosomal recessive congenital ichthyosis is also caused by TGM1 variants; they fall mostly in different places as the Treacher Collins syndrome 2 variants (64 disease-causing).
- Lamellar ichthyosis is also caused by TGM1 variants; they fall mostly in different places as the Treacher Collins syndrome 2 variants (24 disease-causing).
Diseases related to Treacher Collins syndrome 2
- Autosomal recessive congenital ichthyosis, also linked to TGM1
- Lamellar ichthyosis, also linked to TGM1
- Ichthyosis and erythrokeratoderma, also linked to TGM1
- Congenital reticular ichthyosiform erythroderma, also linked to TGM1
Frequently asked questions
Which genes are linked to Treacher Collins syndrome 2?
In CATVariant, Treacher Collins syndrome 2 is linked to 2 analyzed proteins: POLR1D (DNA-directed RNA polymerases I and III subunit RPAC2) and TGM1 (Protein-glutamine gamma-glutamyltransferase K).
How many genetic variants are linked to Treacher Collins syndrome 2?
10 variants: 3 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 2 are of uncertain significance or have conflicting reports.
Which uncertain variants in Treacher Collins syndrome 2 look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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