Acne inversa, familial, 3: genes and variants

Genes linked to Acne inversa, familial, 3

• PSEN1: Presenilin-1

  Its catalytic activity within gamma-secretase cleaves APP and many other membrane proteins, including Notch receptors. Pathogenic variants alter amyloid-beta production and are the most common known cause of autosomal dominant early-onset Alzheimer disease.

  57 disease-causing and 50 uncertain variants in PSEN1 are linked to Acne inversa, familial, 3.

• NCSTN: Nicastrin

  An essential subunit of the gamma-secretase complex, an intramembrane protease that processes proteins such as Notch receptors and APP. Through this complex it contributes to cell-signaling pathways and has relevance to skin disease and amyloid biology.

  1 disease-causing and 4 uncertain variants in NCSTN are linked to Acne inversa, familial, 3.

Where Acne inversa, familial, 3 variants cluster

• PSEN1 Transmembrane (positions 249–272): 10 of 57 disease-causing changes, 3.4× more than its size predicts.
• PSEN1 Transmembrane (positions 133–153): 8 of 57 disease-causing changes, 3.1× more than its size predicts.
• PSEN1 Transmembrane (positions 408–428): 5 of 57 disease-causing changes, 1.9× more than its size predicts.
• PSEN1 Lumenal (positions 104–132): 6 of 57 disease-causing changes, 1.7× more than its size predicts.

Known disease-causing variants in Acne inversa, familial, 3

Uncertain variants in Acne inversa, familial, 3 that look disease-causing

Which prediction tools work for Acne inversa, familial, 3

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

• CATVariant: 96 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• REVEL: 89 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• PolyPhen-2: 89 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 82 out of 100
• phyloP: 78 out of 100
• CADD: 76 out of 100

Same protein, different disease

• Alzheimer disease is also caused by PSEN1 variants; they fall in the same places as the Acne inversa, familial, 3 variants (88 disease-causing).
• Frontotemporal dementia is also caused by PSEN1 variants; they fall partly in the same places as the Acne inversa, familial, 3 variants (63 disease-causing).
• Pick disease is also caused by PSEN1 variants; they fall in the same places as the Acne inversa, familial, 3 variants (26 disease-causing).

Diseases related to Acne inversa, familial, 3

• Telangiectasia, hereditary hemorrhagic, type 2, also linked to PSEN1
• Alzheimer disease, also linked to PSEN1
• Dilated cardiomyopathy, also linked to PSEN1
• Frontotemporal dementia, also linked to PSEN1
• Pick disease, also linked to PSEN1
• Familial isolated dilated cardiomyopathy, also linked to PSEN1
• Dementia, also linked to PSEN1
• Early-onset autosomal dominant Alzheimer disease, also linked to PSEN1

Frequently asked questions

Which genes are linked to Acne inversa, familial, 3?

In CATVariant, Acne inversa, familial, 3 is linked to 2 analyzed proteins: PSEN1 (Presenilin-1) and NCSTN (Nicastrin).

How many genetic variants are linked to Acne inversa, familial, 3?

127 variants: 58 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 54 are of uncertain significance or have conflicting reports.

Which uncertain variants in Acne inversa, familial, 3 look disease-causing?

1 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example PSEN1 A79T. These are leads for expert review, not diagnoses.

Which variant effect predictor works best for Acne inversa, familial, 3?

Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.82, based on 57 disease-causing and 10 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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