FAN1 (Fanconi-associated nuclease 1) variants and mutations

FAN1 (also known as Fanconi-associated nuclease 1) is a human protein-coding gene encoding a fanconi-associated nuclease 1 protein. It processes branched and damaged DNA structures and contributes to repair of interstrand crosslinks and stalled replication intermediates. Biallelic pathogenic variants cause karyomegalic interstitial nephritis, while repeat-length variation in FAN1 modifies age at onset of some repeat-expansion diseases. This analysis covers 1,677 FAN1 variants and mutations. Of these, 82% have computational variant effect predictions. Disease context includes karyomegalic interstitial nephritis, hereditary disease, and chronic kidney disease. Example FAN1 variants include M1?, M1V, and M2I.

Variant analysis overview

Gene: FAN1
Protein: Fanconi-associated nuclease 1
UniProt accession: Q9Y2M0
Organism: Homo sapiens
Variants analyzed: 1677
Variant scope: all variants
Completed: 2026-08-22

Variant and mutation evidence

Variant composition: 1,187 unspecified-consequence records; 172 synonymous variants; 20 in-frame deletions; 228 missense variants; 61 frameshift variants; 7 stop-gained variants; 1 in-frame insertions; 1 substitution
Prediction scores: 1,373 variants have prediction scores (82% of the analyzed set).

Clinical, disease, and population context

Disease context: 25 disease associations are represented. Top associations: karyomegalic interstitial nephritis, hereditary disease, chronic kidney disease, Abnormality of the skeletal system, interstitial nephritis, kidney failure, neurodegenerative disease, skin neoplasm, Tietze syndrome, benign neoplasm of eye, hereditary breast ovarian cancer syndrome, Hereditary breast and ovarian cancer syndrome.

Protein structure and variant hotspots

Protein features: 1 domains; 9 binding sites; 1 post-translational modification sites.
Structural context: 114 variants have structural context.
PTM context: 3 variants overlap post-translational modification sites.

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.

Notable FAN1 variants

Examples include M1?, M1V, M2I, M2L, M2T, S3*, S3L, S3S. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

FAN1 analysis run — FAN1 (1,677 variants) — completed 2026-08-22