Craniosynostosis: genes and variants

Genes linked to Craniosynostosis

• 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 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in FGFR3 have source records linked to Craniosynostosis. Association strength is not clinical gene validity.

• GRIN2B: Glutamate receptor ionotropic, NMDA 2B

  The GluN2B subunit of NMDA glutamate receptors, ion channels that mediate excitatory signaling in the brain. Pathogenic variants can disrupt neuronal development and cause neurodevelopmental disorders, sometimes with epilepsy.

  1 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in GRIN2B have source records linked to Craniosynostosis. Association strength is not clinical gene validity.

• 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 ClinVar pathogenic / likely pathogenic and 6 uncertain variants in FGFR2 have source records linked to Craniosynostosis. Association strength is not clinical gene validity.

• 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 ClinVar pathogenic / likely pathogenic and 6 uncertain variants in FGFR1 have source records linked to Craniosynostosis. Association strength is not clinical gene validity.

Weakly linked (only a few uncertain records): CSF1R, DNMT3A, PTCH1 and TGFBR1.

ClinVar pathogenic and likely pathogenic variants linked to Craniosynostosis

Same protein, different disease

• FGFR3-related chondrodysplasia also has ClinVar records linked to FGFR3 variants; they fall mostly in different places as the Craniosynostosis variants (20 pathogenic / likely pathogenic).
• Hypochondroplasia also has ClinVar records linked to FGFR3 variants; they fall mostly in different places as the Craniosynostosis variants (15 pathogenic / likely pathogenic).
• Achondroplasia also has ClinVar records linked to FGFR3 variants; they fall mostly in different places as the Craniosynostosis variants (9 pathogenic / likely pathogenic).
• Thanatophoric dysplasia also has ClinVar records linked to FGFR3 variants; they fall mostly in different places as the Craniosynostosis variants (8 pathogenic / likely pathogenic).
• Severe achondroplasia - developmental delay - acanthosis nigricans also has ClinVar records linked to FGFR3 variants; they fall mostly in different places as the Craniosynostosis variants (5 pathogenic / likely pathogenic).
• Complex neurodevelopmental disorder also has ClinVar records linked to GRIN2B variants; they fall mostly in different places as the Craniosynostosis variants (5 pathogenic / likely pathogenic).

Diseases related to Craniosynostosis

• 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
• LADD 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 disease, also linked to FGFR2
• Connective tissue disease, also linked to FGFR3

Frequently asked questions

Which genes have records linked to Craniosynostosis?

This view contains 4 analyzed proteins: FGFR3, GRIN2B, FGFR2, FGFR1. Links come from clinical records and association databases. They do not imply that every listed gene is a validated cause, and missing genes may not yet be analyzed.

What do the clinical classifications mean?

Linked records include 2 pathogenic or likely pathogenic variants, 6 variants of uncertain significance and 10 with conflicting classifications. Labels summarize source records; multi-condition records may not make a separate assertion for this disease. Check the original record and review status.

Does the evidence score change a VUS classification?

No. 0 VUS or conflicting variants reach the likely-pathogenic points range on the computable criteria available here. This is a research prioritization signal, not a clinical classification. Patient, family and other required evidence may be missing.

Can I download the variant evidence?

Download the CSV for all 22 variants in the selected disease scope, including clinical labels, review status, evidence criteria, predictor scores, functional measurements and population frequency where available.

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from eligible public CATVariant analyses 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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