Hartsfield-Bixler-Demyer syndrome: genes and variants

Genes linked to Hartsfield-Bixler-Demyer 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.

  13 disease-causing and 42 uncertain variants in FGFR1 are linked to Hartsfield-Bixler-Demyer syndrome.

Where Hartsfield-Bixler-Demyer syndrome variants cluster

• FGFR1 Protein kinase (positions 478–767): 11 of 13 disease-causing changes, 2.4× more than its size predicts.

Known disease-causing variants in Hartsfield-Bixler-Demyer syndrome

Which prediction tools work for Hartsfield-Bixler-Demyer syndrome

How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).

• CATVariant: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• PolyPhen-2: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 91 out of 100

Same protein, different disease

• Hypogonadotropic hypogonadism 2 with or without anosmia is also caused by FGFR1 variants; they fall mostly in different places as the Hartsfield-Bixler-Demyer syndrome variants (55 disease-causing).
• Pfeiffer syndrome is also caused by FGFR1 variants; they fall mostly in different places as the Hartsfield-Bixler-Demyer syndrome variants (18 disease-causing).
• Jackson-Weiss syndrome is also caused by FGFR1 variants; they fall mostly in different places as the Hartsfield-Bixler-Demyer syndrome variants (5 disease-causing).
• Osteoglophonic dysplasia is also caused by FGFR1 variants; they fall mostly in different places as the Hartsfield-Bixler-Demyer syndrome variants (5 disease-causing).
• Hypogonadotropic hypogonadism 7 with or without anosmia is also caused by FGFR1 variants; they fall mostly in different places as the Hartsfield-Bixler-Demyer syndrome variants (3 disease-causing).

Diseases related to Hartsfield-Bixler-Demyer syndrome

• Hypogonadotropic hypogonadism 2 with or without anosmia, also linked to FGFR1
• Pfeiffer syndrome, also linked to FGFR1
• Colorectal cancer, also linked to FGFR1
• Non-small cell lung carcinoma, also linked to FGFR1
• Idiopathic pulmonary fibrosis, also linked to FGFR1
• Jackson-Weiss syndrome, also linked to FGFR1
• Encephalocraniocutaneous lipomatosis, also linked to FGFR1
• Osteoglophonic dysplasia, also linked to FGFR1
• Renal cell carcinoma, also linked to FGFR1
• Hypogonadotropic hypogonadism, also linked to FGFR1
• Craniosynostosis syndrome, also linked to FGFR1
• Interstitial lung disease, also linked to FGFR1

Frequently asked questions

Which genes are linked to Hartsfield-Bixler-Demyer syndrome?

In CATVariant, Hartsfield-Bixler-Demyer syndrome is linked to 1 analyzed protein: FGFR1 (Fibroblast growth factor receptor 1).

How many genetic variants are linked to Hartsfield-Bixler-Demyer syndrome?

68 variants: 13 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 42 are of uncertain significance or have conflicting reports.

Which uncertain variants in Hartsfield-Bixler-Demyer syndrome look disease-causing?

None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.

Which variant effect predictor works best for Hartsfield-Bixler-Demyer syndrome?

Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.91, based on 11 disease-causing and 19 harmless variants).

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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