Hyper-IgE recurrent infection syndrome 1, autosomal dominant: genes and variants

Genes linked to Hyper-IgE recurrent infection syndrome 1, autosomal dominant

• STAT3: Signal transducer and activator of transcription 3

  It translates cytokine and growth-factor signals into transcriptional programs governing immune regulation, survival, proliferation, and tissue repair. Dominant-negative variants cause hyper-IgE syndrome, while activating germline variants cause early autoimmunity and lymphoproliferation and somatic activation contributes to cancer.

  65 disease-causing and 177 uncertain variants in STAT3 are linked to Hyper-IgE recurrent infection syndrome 1, autosomal dominant.

• IL6R: Interleukin-6 receptor subunit alpha

  It binds IL-6 and signals through gp130 either from the cell surface or as a soluble receptor, allowing both classical and trans-signaling. Genetic and pharmacologic reduction of IL-6 receptor signaling lowers inflammatory activity and is therapeutically useful in several immune-mediated diseases.

  0 disease-causing and 3 uncertain variants in IL6R are linked to Hyper-IgE recurrent infection syndrome 1, autosomal dominant.

• DOCK8: Dedicator of cytokinesis protein 8

  It coordinates actin remodeling and signaling required for migration, survival, and immune synapse formation in lymphocytes. Biallelic loss-of-function variants cause DOCK8 deficiency, a combined immunodeficiency characterized by severe viral infections, allergy, eczema, and malignancy risk.

  0 disease-causing and 86 uncertain variants in DOCK8 are linked to Hyper-IgE recurrent infection syndrome 1, autosomal dominant.

Weakly linked (only a few uncertain records): ITGB3.

Where Hyper-IgE recurrent infection syndrome 1, autosomal dominant variants cluster

• STAT3 SH2 (positions 580–670): 22 of 65 disease-causing changes, 2.9× more than its size predicts.

Known disease-causing variants in Hyper-IgE recurrent infection syndrome 1, autosomal dominant

Showing 60 of 65.

Uncertain variants in Hyper-IgE recurrent infection syndrome 1, autosomal dominant that look disease-causing

Which prediction tools work for Hyper-IgE recurrent infection syndrome 1, autosomal dominant

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

• AlphaMissense: 97 out of 100
• MetaLR: 91 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• REVEL: 90 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CATVariant: 89 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CADD: 86 out of 100
• MutPred2: 83 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 80 out of 100
• PolyPhen-2: 75 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• phyloP: 69 out of 100
• EVE: 64 out of 100

Same protein, different disease

• STAT3-related early-onset multisystem autoimmune disease is also caused by STAT3 variants; they fall partly in the same places as the Hyper-IgE recurrent infection syndrome 1, autosomal dominant variants (21 disease-causing).

Diseases related to Hyper-IgE recurrent infection syndrome 1, autosomal dominant

• Inherited Immunodeficiency Diseases, also linked to DOCK8 and STAT3
• STAT3 gain of function, also linked to STAT3
• Severe combined immunodeficiency disease, also linked to DOCK8
• STAT3-related early-onset multisystem autoimmune disease, also linked to STAT3
• Hyper-IgE syndrome 6, autosomal dominant, with recurrent infections, also linked to STAT3
• Combined immunodeficiency due to DOCK8 deficiency, also linked to DOCK8

Frequently asked questions

Which genes are linked to Hyper-IgE recurrent infection syndrome 1, autosomal dominant?

In CATVariant, Hyper-IgE recurrent infection syndrome 1, autosomal dominant is linked to 3 analyzed proteins: STAT3 (Signal transducer and activator of transcription 3), IL6R (Interleukin-6 receptor subunit alpha) and DOCK8 (Dedicator of cytokinesis protein 8).

How many genetic variants are linked to Hyper-IgE recurrent infection syndrome 1, autosomal dominant?

366 variants: 65 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 266 are of uncertain significance or have conflicting reports.

Which uncertain variants in Hyper-IgE recurrent infection syndrome 1, autosomal dominant look disease-causing?

3 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example STAT3 G618R, STAT3 R335Q and STAT3 G421E. These are leads for expert review, not diagnoses.

Which variant effect predictor works best for Hyper-IgE recurrent infection syndrome 1, autosomal dominant?

Among tools not trained on clinical labels, AlphaMissense separates this disease's known disease-causing variants from harmless ones best (AUROC 0.97, based on 48 disease-causing and 31 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.

Download every variant as CSV · Browse all diseases · Methods · About the Center