Kennedy disease: genes and variants

Genes linked to Kennedy disease

• AR: Androgen receptor

  Androgen binding redirects its transcriptional program to control male sexual differentiation, reproductive physiology, muscle and bone biology, and other androgen-responsive processes. Loss-of-function variants cause androgen insensitivity, CAG expansion causes spinal and bulbar muscular atrophy, and persistent signaling drives prostate cancer.

  46 disease-causing and 70 uncertain variants in AR are linked to Kennedy disease.

Where Kennedy disease variants cluster

• AR Interaction with LPXN (positions 552–919): 45 of 46 disease-causing changes, 2.5× more than its size predicts.

Known disease-causing variants in Kennedy disease

Which prediction tools work for Kennedy disease

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

• CATVariant: 95 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• AlphaMissense: 92 out of 100
• MetaLR: 92 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• EVE: 88 out of 100
• PolyPhen-2: 84 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 80 out of 100

Same protein, different disease

• Androgen resistance syndrome is also caused by AR variants; they fall partly in the same places as the Kennedy disease variants (85 disease-causing).
• Differences in sex development is also caused by AR variants; they fall in the same places as the Kennedy disease variants (9 disease-causing).
• Male infertility is also caused by AR variants; they fall partly in the same places as the Kennedy disease variants (7 disease-causing).
• Partial androgen insensitivity syndrome is also caused by AR variants; they fall in the same places as the Kennedy disease variants (7 disease-causing).
• Ovarian cancer is also caused by AR variants; they fall mostly in different places as the Kennedy disease variants (4 disease-causing).

Diseases related to Kennedy disease

• Androgen resistance syndrome, also linked to AR
• Ovarian cancer, also linked to AR
• Differences in sex development, also linked to AR
• Male infertility with azoospermia or oligozoospermia due to single gene mutation, also linked to AR
• Male infertility, also linked to AR
• Partial androgen insensitivity syndrome, also linked to AR
• Disorder of sexual differentiation, also linked to AR
• Prostate cancer, also linked to AR
• Hypospadias, also linked to AR

Frequently asked questions

Which genes are linked to Kennedy disease?

In CATVariant, Kennedy disease is linked to 1 analyzed protein: AR (Androgen receptor).

How many genetic variants are linked to Kennedy disease?

134 variants: 46 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 70 are of uncertain significance or have conflicting reports.

Which uncertain variants in Kennedy disease 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 Kennedy disease?

Among tools not trained on clinical labels, AlphaMissense separates this disease's known disease-causing variants from harmless ones best (AUROC 0.93, based on 36 disease-causing and 25 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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