Meier-Gorlin syndrome: genes and variants
Meier-Gorlin syndrome is linked to 2 analyzed proteins (ORC1 and MCM5). 7 DNA variants are known to cause it; 33 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: Meier-Gorlin syndrome 1; Meier-Gorlin syndrome 8
Genes linked to Meier-Gorlin syndrome
ORC1: Origin recognition complex subunit 1
It helps mark replication origins and assemble the prereplication complex needed to license DNA replication once per cell cycle. Biallelic pathogenic variants cause Meier-Gorlin syndrome, characterized by severe growth restriction, microtia, and absent or small patellae.
6 disease-causing and 31 uncertain variants in ORC1 are linked to Meier-Gorlin syndrome.
MCM5: DNA replication licensing factor MCM5
It functions within the MCM2-7 helicase complex required for origin licensing and DNA unwinding during replication. Because its expression tracks proliferative activity, altered abundance is frequently observed in cancers and is used as a proliferation-related biomarker.
1 disease-causing and 1 uncertain variants in MCM5 are linked to Meier-Gorlin syndrome.
Weakly linked (only a few uncertain records): MCM3.
Where Meier-Gorlin syndrome variants cluster
- ORC1 BAH (positions 45–171): 4 of 6 disease-causing changes, 4.5× more than its size predicts.
Known disease-causing variants in Meier-Gorlin syndrome
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| ORC1 R105W | 105 | BAH | Disease-causing (★★) |
| ORC1 R105Q | 105 | BAH | Disease-causing (★★) |
| ORC1 L622P | 622 | Necessary and sufficient for ORC complex assembl | Disease-causing (★) |
| ORC1 E73K | 73 | BAH | Disease-causing (★) |
| MCM5 T466I | 466 | MCM C-terminal AAA(+) ATPase | Disease-causing |
| ORC1 E127G | 127 | BAH | Disease-causing |
| ORC1 S828F | 828 | Necessary and sufficient for ORC complex assembl | Disease-causing |
Diseases related to Meier-Gorlin syndrome
- Fetal anomalies with a likely genetic cause, also linked to ORC1
Frequently asked questions
Which genes are linked to Meier-Gorlin syndrome?
In CATVariant, Meier-Gorlin syndrome is linked to 2 analyzed proteins: ORC1 (Origin recognition complex subunit 1) and MCM5 (DNA replication licensing factor MCM5).
How many genetic variants are linked to Meier-Gorlin syndrome?
52 variants: 7 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 33 are of uncertain significance or have conflicting reports.
Which uncertain variants in Meier-Gorlin syndrome 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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