Hypogonadotropic hypogonadism 2 with or without anosmia: genes and variants

Genes linked to Hypogonadotropic hypogonadism 2 with or without anosmia

• 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.

  55 disease-causing and 320 uncertain variants in FGFR1 are linked to Hypogonadotropic hypogonadism 2 with or without anosmia.

Known disease-causing variants in Hypogonadotropic hypogonadism 2 with or without anosmia

Uncertain variants in Hypogonadotropic hypogonadism 2 with or without anosmia that look disease-causing

Which prediction tools work for Hypogonadotropic hypogonadism 2 with or without anosmia

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

• PolyPhen-2: 97 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CATVariant: 97 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• REVEL: 97 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 96 out of 100
• CADD: 93 out of 100
• phyloP: 65 out of 100

Same protein, different disease

• Hartsfield-Bixler-Demyer syndrome is also caused by FGFR1 variants; they fall mostly in different places as the Hypogonadotropic hypogonadism 2 with or without anosmia variants (13 disease-causing).
• Osteoglophonic dysplasia is also caused by FGFR1 variants; they fall partly in the same places as the Hypogonadotropic hypogonadism 2 with or without anosmia variants (5 disease-causing).
• Encephalocraniocutaneous lipomatosis is also caused by FGFR1 variants; they fall partly in the same places as the Hypogonadotropic hypogonadism 2 with or without anosmia variants (3 disease-causing).

Diseases related to Hypogonadotropic hypogonadism 2 with or without anosmia

• 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
• Hartsfield-Bixler-Demyer syndrome, 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 Hypogonadotropic hypogonadism 2 with or without anosmia?

In CATVariant, Hypogonadotropic hypogonadism 2 with or without anosmia is linked to 1 analyzed protein: FGFR1 (Fibroblast growth factor receptor 1).

How many genetic variants are linked to Hypogonadotropic hypogonadism 2 with or without anosmia?

422 variants: 55 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 320 are of uncertain significance or have conflicting reports.

Which uncertain variants in Hypogonadotropic hypogonadism 2 with or without anosmia look disease-causing?

3 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example FGFR1 G610S, FGFR1 A671V and FGFR1 C101W. These are leads for expert review, not diagnoses.

Which variant effect predictor works best for Hypogonadotropic hypogonadism 2 with or without anosmia?

Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.96, based on 46 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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