LCT across dismech

LCT (lactase) encodes lactase-phlorizin hydrolase, the brush-border enzyme that hydrolyses dietary lactose. It is named by 2 disorder entries, which reach a loss of lactase activity by two different routes: Adult-Type Hypolactasia; and Congenital Lactase Deficiency.

Two routes to the same enzyme deficit

Both entries type LCT as causative (Adult-Type Hypolactasia; and Congenital Lactase Deficiency), and both record the variants as germline (Adult-Type Hypolactasia; and Congenital Lactase Deficiency).

In Congenital Lactase Deficiency the lesion is in the enzyme itself: coding variants inactivate it, and the gene sits on the node LCT Loss-of-Function and Absent Lactase-Phlorizin Hydrolase Activity, which conforms to the module for loss of a brush-border digestive step, diet_induced_osmotic_diarrhea.

In Adult-Type Hypolactasia the enzyme is normal and its expression is not maintained after weaning. The causal variants lie in an enhancer inside an intron of the neighbouring MCM6 gene, so that entry records the enhancer as an affected region with MCM6 as its host, and names LCT as the regulatory target of the C/T-13910 variant. LCT then appears on two nodes: Reduced Enterocyte LCT Transcription and Declining Intestinal Lactase Activity.

Where the layers disagree

ClinGen classifies LCT for 0 diseases, so neither entry's typing can be checked against an external validity curation.

The pinned ai-gene-review ingest carries no core functions for LCT yet (0 terms), so the KB's LCT nodes share 0 GO terms with it. The upstream review is being completed with lactase activity and lactose catabolic process as the core function, which matches the lactase-activity node that Adult-Type Hypolactasia marks as decreased; the overlap will appear once the ingest is refreshed.