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Generalized Arterial Calcification of Infancy (GACI) is a rare, autosomal recessive disorder characterised by early and widespread calcification of large- and medium-sized arteries. While biallelic ENPP1 variants account for the majority of GACI type I cases, pathogenic variants in ABCC6 have been implicated in the minority of patients with GACI type II, suggesting allelic and locus heterogeneity in disease causation (PMID:34199854).
Genetic evidence for ABCC6 in GACI type II remains limited, with a single cohort study noting ABCC6 as a lesser contributor without reporting independent ABCC6‐only probands or detailed segregation. No ABCC6 variants have been functionally characterised in the context of infantile arterial calcification, and mechanistic data are currently lacking. Further targeted sequencing in GACI cohorts and in vitro assessment of candidate ABCC6 missense or loss-of-function alleles are needed to establish pathogenicity.
Key take-home: ABCC6 is a rare, recessive contributor to GACI type II, warranting inclusion in diagnostic panels and further functional studies to guide prognosis and therapeutic development.
Gene–Disease AssociationLimitedSingle study mentions ABCC6 as a minor cause of GACI type II; no independent ABCC6‐only probands reported Genetic EvidenceLimitedOne cohort reference implicating ABCC6 without detailed variant or segregation data Functional EvidenceNo EvidenceNo experimental or functional data for ABCC6 in arterial calcification models |