LBR across dismech

LBR (lamin B receptor) encodes an inner nuclear membrane protein whose C-terminal domain is an NADPH-dependent sterol C14 reductase of post-squalene cholesterol synthesis and whose nucleoplasmic domain tethers heterochromatin and the lamina to the nuclear envelope. It is named by 3 disorder entries: Greenberg Dysplasia; Pelger-Huet Anomaly; and Reynolds Syndrome.

The enzymatic phenotype

Greenberg Dysplasia types LBR as causative, with a germline origin and a loss of function impact. The gene sits on the node LBR Sterol C14-Reductase Deficiency, and the process the KB marks as decreased on LBR's nodes is cholesterol biosynthetic process. ClinGen rates LBR moderate for Greenberg dysplasia.

The structural phenotype

Pelger-Huet Anomaly, the heterozygous nuclear-shape phenotype, also types LBR as causative and places it on LBR Loss-of-Function Allele, with its variant origin recorded as germline. Reynolds Syndrome types LBR as a susceptibility gene.

Where the layers disagree

ClinGen classifies LBR for 2 diseases, and the one with no dismech entry is regressive spondylometaphyseal dysplasia.

The pinned ai-gene-review ingest has no review of LBR (0 core-function terms), so the KB's LBR nodes share 0 GO terms with it. A new upstream review gives Delta14-sterol reductase activity in cholesterol biosynthesis as the core function, which matches the KB's deficiency node once the ingest is refreshed.