Levy-Hollister syndrome: genes and variants
Levy-Hollister syndrome is linked to 2 analyzed proteins (FGFR2 and FGFR3). 5 DNA variants are known to cause it; 10 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Levy-Hollister syndrome
FGFR2: Fibroblast growth factor receptor 2
Its fibroblast-growth-factor signaling regulates proliferation, differentiation, and developmental patterning across multiple tissues. Germline activating variants cause several craniosynostosis syndromes, while somatic mutations, amplification, or fusions can drive cancer.
5 disease-causing and 4 uncertain variants in FGFR2 are linked to Levy-Hollister syndrome.
FGFR3: Fibroblast growth factor receptor 3
It normally restrains growth-plate chondrocyte proliferation while regulating multiple developmental pathways. Activating germline variants cause achondroplasia and related skeletal dysplasias, while somatic activating alterations are common in bladder cancer and some other tumors.
0 disease-causing and 6 uncertain variants in FGFR3 are linked to Levy-Hollister syndrome.
Where Levy-Hollister syndrome variants cluster
- FGFR2 Protein kinase (positions 481–770): 5 of 5 disease-causing changes, 2.8× more than its size predicts.
Known disease-causing variants in Levy-Hollister syndrome
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| FGFR2 A648T | 648 | Protein kinase | Disease-causing (★★) |
| FGFR2 G493W | 493 | Protein kinase | Disease-causing (★) |
| FGFR2 A674V | 674 | Protein kinase | Disease-causing (★) |
| FGFR2 A515V | 515 | Protein kinase | Disease-causing |
| FGFR2 E534K | 534 | Protein kinase | Disease-causing |
Same protein, different disease
- FGFR2-related craniosynostosis is also caused by FGFR2 variants; they fall mostly in different places as the Levy-Hollister syndrome variants (54 disease-causing).
- Crouzon syndrome is also caused by FGFR2 variants; they fall mostly in different places as the Levy-Hollister syndrome variants (22 disease-causing).
- Pfeiffer syndrome is also caused by FGFR2 variants; they fall mostly in different places as the Levy-Hollister syndrome variants (13 disease-causing).
- Acrocephalosyndactyly type I is also caused by FGFR2 variants; they fall mostly in different places as the Levy-Hollister syndrome variants (6 disease-causing).
- Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis is also caused by FGFR2 variants; they fall mostly in different places as the Levy-Hollister syndrome variants (5 disease-causing).
Diseases related to Levy-Hollister syndrome
- Colorectal cancer, also linked to FGFR2 and FGFR3
- Common craniosynostosis syndromes, also linked to FGFR2 and FGFR3
- Craniosynostosis syndrome, also linked to FGFR2 and FGFR3
- FGFR2-related craniosynostosis, also linked to FGFR2
- Pfeiffer syndrome, also linked to FGFR2
- Crouzon syndrome, also linked to FGFR2
- Connective tissue disorder, also linked to FGFR3
- FGFR3-related chondrodysplasia, also linked to FGFR3
- Gastric cancer, also linked to FGFR2
- Malignant tumor of urinary bladder, also linked to FGFR3
- Hypochondroplasia, also linked to FGFR3
- Carcinoma of colon, also linked to FGFR3
Frequently asked questions
Which genes are linked to Levy-Hollister syndrome?
In CATVariant, Levy-Hollister syndrome is linked to 2 analyzed proteins: FGFR2 (Fibroblast growth factor receptor 2) and FGFR3 (Fibroblast growth factor receptor 3).
How many genetic variants are linked to Levy-Hollister syndrome?
16 variants: 5 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 10 are of uncertain significance or have conflicting reports.
Which uncertain variants in Levy-Hollister 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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