POR (NADPH--cytochrome P450 reductase) variants and mutations

POR (also known as NADPH--cytochrome P450 reductase) is a human protein-coding gene encoding a NADPH--cytochrome P450 reductase protein. It transfers electrons from NADPH to microsomal cytochrome P450 enzymes, making it essential for steroid synthesis and metabolism of many drugs and xenobiotics. Biallelic pathogenic variants cause P450 oxidoreductase deficiency, with disordered steroidogenesis and skeletal abnormalities. This analysis covers 1,007 POR variants and mutations. Of these, 34% have computational variant effect predictions. Disease context includes congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency, Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis, and congenital adrenal hyperplasia. Example POR variants include M1V, M1T, and M1I.

Variant analysis overview

Gene: POR
Protein: NADPH--cytochrome P450 reductase
UniProt accession: P16435
Organism: Homo sapiens
Variants analyzed: 1007
Variant scope: all variants
Completed: 2026-08-19

Variant and mutation evidence

Variant composition: 878 unspecified-consequence records; 76 missense variants; 28 synonymous variants; 6 stop-gained variants; 8 frameshift variants; 4 in-frame deletions; 2 splice-region variants; 5 substitution
Prediction scores: 343 variants have prediction scores (34% of the analyzed set).

Clinical, disease, and population context

Disease context: 25 disease associations are represented. Top associations: congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency, Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis, congenital adrenal hyperplasia, Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis, coffee consumption, hereditary disease, autoimmune disorder of central nervous system, ovarian neoplasm, substance-related disorder, Fine-Lubinsky syndrome, primary ovarian failure, Abnormality of the skeletal system.

Protein structure and variant hotspots

Protein features: 1 transmembrane segments; 2 domains; 15 binding sites; 2 post-translational modification sites.
Structural context: 558 variants have structural context.
PTM context: 7 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 POR variants

Examples include M1V, M1T, M1I, G2A, G2R, G2*, G2G, G2V. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

POR analysis run — POR (1,007 variants) — completed 2026-08-19