has material basis in gain of function germline mutation in CPOX inherited porphyria CPOX-related hereditary coproporphyria https://github.com/monarch-initiative/mondo/issues/5474 https://github.com/monarch-initiative/mondo/issues/9703 A porphyria caused by monoallelic and biallelic variants in CPOX and presenting as a spectrum of disease (a semidominant inheritance pattern). Monoallelic variants typically cause acute/episodic neurovisceral attacks with adolescent or adult onset, characterized by severe abdominal pain as well as acute motor neuropathy and other neurological symptoms. Triggers precipitating acute attacks include estrogen/progesterone, oral contraceptives, alcohol, drugs, stress, or infections. Cases with biallelic variants have symptoms in infancy, including hemolytic anemia, enlarged liver and spleen (hepatosplenomegaly), and severe jaundice. Additional symptoms may include erythrodontia, red urine, fragile skin, and cutaneous photosensitivity leading to scarring of sun-exposed skin. CPOX-related hepatic porphyria Per criteria outlined by the ClinGen Lumping and Splitting Working Group, the molecular mechanism (CPOX loss-of-function) was found to be consistent between the harderoporphyria cases and hereditary coproporphyria cases. In addition, the phenotypic differences between the biallelic and monoallelic cases appeared to represent a single spectrum of disease. Therefore, cases caused by inherited CPOX variants have been lumped into a single disease entity referred to as CPOX-related hereditary coproporphyria, with a semidominant mode of inheritance. MONDO:0800180 GARD:0026471