SIM1 across dismech

SIM1 (SIM bHLH transcription factor 1) is named by 2 disorder entries.

How the entries record the gene

Both entries type SIM1 as causative (6q16 Deletion Syndrome; Obesity Due to MC4R Pathway Disruption), with germline variants in each (germline in the obesity entry, germline in the deletion syndrome). No record is left untyped (0). ClinGen's gene-disease validity table classifies SIM1 for 0 diseases, so the typing rests on the entries' own cited evidence.

Where the gene sits in the pathograph

In Obesity Due to MC4R Pathway Disruption SIM1 is one of several genes on the shared node MC4R pathway signaling failure, whose GO terms describe receptor-level signalling; SIM1 enters that chain as the transcription factor that builds and maintains the melanocortin-responsive neurons of the paraventricular nucleus, so none of the node's GO terms is its own function. In 6q16 Deletion Syndrome it is bound to two nodes of its own (Reduced SIM1 Gene Dosage; Reduced SIM1-Dependent Transactivation), which carry no GO term yet. The only process on any node naming SIM1 is adenylate cyclase-activating G protein-coupled receptor signaling pathway.

No node naming SIM1 declares conformance to a mechanism module (0), and no treatment record names the gene (0).

Normal function

The ai-gene-review ingest layer currently reports 0 core function terms for SIM1, because the ingest tables are pinned to an ai-gene-review commit that predates the review of this gene. The upstream review, written in the same round of work as this page, gives RNA polymerase II-specific DNA-binding transcription factor activity in the nucleus, as a heterodimer with ARNT2, driving terminal differentiation of hypothalamic paraventricular and supraoptic neuroendocrine neurons, as the core function. That transcription-factor activity is the natural GO binding for the 6q16 "Reduced SIM1-Dependent Transactivation" node.