HEPACAM

Chr 11

hepatic and glial cell adhesion molecule

Also known as: GlialCAM, MLC2A, MLC2B

NCBI Gene: 220296 ENSG00000165478 UniProt: Q14CZ8

HEPACAM encodes a membrane protein that regulates cell motility and cell-matrix interactions, and in glia it targets the chloride channel CLCN2 to astrocytic processes where it regulates chloride flux involved in neuronal excitability. Mutations cause megalencephalic leukoencephalopathy with subcortical cysts, which can present as either a severe progressive form (type 2A) or a milder remitting form (type 2B) that may occur with or without intellectual disability. The gene shows high constraint against loss-of-function variants and follows both autosomal recessive and autosomal dominant inheritance patterns.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a single-pass type I membrane protein that localizes to the cytoplasmic side of the cell membrane. The encoded protein acts as a homodimer and is involved in cell motility and cell-matrix interactions. The expression of this gene is downregulated or undetectable in many cancer cell lines, so this may be a tumor suppressor gene. [provided by RefSeq, Jul 2011]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtMegalencephalic leukoencephalopathy with subcortical cysts 2A

UniProtMegalencephalic leukoencephalopathy with subcortical cysts 2B, remitting, with or without impaired intellectual development

Clinical highlights

Gene-disease validity (ClinGen)

megalencephalic leukoencephalopathy with subcortical cysts 2B, remitting, with or without intellectual disability · ADDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.41

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — HEPACAM