Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1: genes and variants

Genes linked to Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1

• TERT: Telomerase reverse transcriptase

  It extends telomeric DNA using an internal RNA template and helps counter progressive chromosome-end shortening in stem and proliferative cells. Loss-of-function variants cause telomere-biology disorders, while promoter activation and increased activity support unlimited proliferation in many cancers.

  13 disease-causing and 30 uncertain variants in TERT are linked to Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1.

• RPA1: Replication protein A 70 kDa DNA-binding subunit

  It binds single-stranded DNA during replication, recombination, and repair, protecting exposed DNA and coordinating checkpoint and repair proteins. Rare pathogenic variants can cause telomere and genome-maintenance disorders, while somatic dysregulation contributes to replication-stress tolerance in cancer.

  2 disease-causing and 3 uncertain variants in RPA1 are linked to Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1.

Weakly linked (only a few uncertain records): SCN2A.

Where Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1 variants cluster

• TERT Reverse transcriptase (positions 605–935): 8 of 13 disease-causing changes, 2.1× more than its size predicts.

Known disease-causing variants in Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1

Which prediction tools work for Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1

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

• REVEL: 88 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• PolyPhen-2: 86 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CADD: 85 out of 100
• CATVariant: 79 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• phyloP: 71 out of 100
• SIFT: 67 out of 100
• MetaLR: 66 out of 100 (learned from overlapping clinical labels, so this is optimistic)

Same protein, different disease

• Dyskeratosis congenita is also caused by TERT variants; they fall mostly in different places as the Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1 variants (23 disease-causing).
• Idiopathic pulmonary fibrosis is also caused by TERT variants; they fall mostly in different places as the Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1 variants (13 disease-causing).

Diseases related to Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1

• Acute myeloid leukemia, also linked to TERT
• Dyskeratosis congenita, also linked to TERT
• Familial melanoma, also linked to TERT
• Idiopathic pulmonary fibrosis, also linked to TERT
• Melanoma, cutaneous malignant, susceptibility to, 8, also linked to TERT
• Lung adenocarcinoma, also linked to TERT
• Hepatocellular carcinoma, also linked to TERT
• Prostate cancer, also linked to TERT
• Myelodysplastic syndrome, also linked to TERT
• Lung carcinoma, also linked to TERT
• Interstitial lung disease, also linked to TERT

Frequently asked questions

Which genes are linked to Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1?

In CATVariant, Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1 is linked to 2 analyzed proteins: TERT (Telomerase reverse transcriptase) and RPA1 (Replication protein A 70 kDa DNA-binding subunit).

How many genetic variants are linked to Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1?

55 variants: 15 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 34 are of uncertain significance or have conflicting reports.

Which uncertain variants in Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1 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 Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1?

Among tools not trained on clinical labels, CADD separates this disease's known disease-causing variants from harmless ones best (AUROC 0.85, based on 8 disease-causing and 48 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