Craniosynostosis syndrome: genes and variants
Craniosynostosis syndrome is linked to 4 analyzed proteins (FGFR3, GRIN2B, FGFR1 and FGFR2). 2 DNA variants are known to cause it; 16 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 Craniosynostosis 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.
1 disease-causing and 0 uncertain variants in FGFR3 are linked to Craniosynostosis syndrome.
GRIN2B: Glutamate receptor ionotropic, NMDA 2B
It confers distinct developmental and signaling properties on NMDA receptors and is highly expressed during early brain development. De novo pathogenic variants can cause intellectual disability, developmental delay, epilepsy, abnormal movements, and autism-related phenotypes.
1 disease-causing and 0 uncertain variants in GRIN2B are linked to Craniosynostosis syndrome.
FGFR1: Fibroblast growth factor receptor 1
Its fibroblast-growth-factor signaling controls proliferation, differentiation, migration, and developmental patterning in many tissues. Germline pathogenic variants can cause hypogonadotropic hypogonadism or craniosynostosis syndromes, while fusions and other activating alterations drive selected cancers.
0 disease-causing and 6 uncertain variants in FGFR1 are linked to Craniosynostosis 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.
0 disease-causing and 6 uncertain variants in FGFR2 are linked to Craniosynostosis syndrome.
Weakly linked (only a few uncertain records): CSF1R, DNMT3A, PTCH1 and TGFBR1.
Known disease-causing variants in Craniosynostosis syndrome
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| FGFR3 P250R | 250 | Extracellular | Disease-causing (★★) |
| GRIN2B M739R | 739 | Extracellular | Disease-causing (★) |
Same protein, different disease
- FGFR3-related chondrodysplasia is also caused by FGFR3 variants; they fall mostly in different places as the Craniosynostosis syndrome variants (20 disease-causing).
- Hypochondroplasia is also caused by FGFR3 variants; they fall mostly in different places as the Craniosynostosis syndrome variants (15 disease-causing).
- Achondroplasia is also caused by FGFR3 variants; they fall mostly in different places as the Craniosynostosis syndrome variants (9 disease-causing).
- Thanatophoric dysplasia is also caused by FGFR3 variants; they fall mostly in different places as the Craniosynostosis syndrome variants (8 disease-causing).
- Severe achondroplasia-developmental delay-acanthosis nigricans syndrome is also caused by FGFR3 variants; they fall mostly in different places as the Craniosynostosis syndrome variants (5 disease-causing).
- Complex neurodevelopmental disorder is also caused by GRIN2B variants; they fall mostly in different places as the Craniosynostosis syndrome variants (5 disease-causing).
Diseases related to Craniosynostosis syndrome
- Colorectal cancer, also linked to FGFR1, FGFR2 and FGFR3
- Pfeiffer syndrome, also linked to FGFR1 and FGFR2
- Jackson-Weiss syndrome, also linked to FGFR1 and FGFR2
- Common craniosynostosis syndromes, also linked to FGFR2 and FGFR3
- Levy-Hollister syndrome, also linked to FGFR2 and FGFR3
- Renal cell carcinoma, also linked to FGFR1 and FGFR3
- Alzheimer disease, also linked to GRIN2B
- Hypogonadotropic hypogonadism 2 with or without anosmia, also linked to FGFR1
- FGFR2-related craniosynostosis, also linked to FGFR2
- Complex neurodevelopmental disorder, also linked to GRIN2B
- Crouzon syndrome, also linked to FGFR2
- Connective tissue disorder, also linked to FGFR3
Frequently asked questions
Which genes are linked to Craniosynostosis syndrome?
In CATVariant, Craniosynostosis syndrome is linked to 4 analyzed proteins: FGFR3 (Fibroblast growth factor receptor 3), GRIN2B (Glutamate receptor ionotropic, NMDA 2B), FGFR1 (Fibroblast growth factor receptor 1) and FGFR2 (Fibroblast growth factor receptor 2).
How many genetic variants are linked to Craniosynostosis syndrome?
22 variants: 2 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 16 are of uncertain significance or have conflicting reports.
Which uncertain variants in Craniosynostosis 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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