FEM1C

Chr 5

fem-1 homolog C

Also known as: EUROIMAGE686608, EUROIMAGE783647, FEM1A

NCBI Gene: 56929 ENSG00000145780 UniProt: Q96JP0 OMIM: 608767

The protein serves as a substrate-recognition component of a Cul2-RING E3 ubiquitin ligase complex that targets proteins with specific C-terminal degrons for ubiquitination and degradation. Mutations in FEM1C cause autosomal recessive intellectual disability with seizures and hypotonia. This gene shows significant constraint against loss-of-function variants (LOEUF 0.479), suggesting that complete protein loss is likely pathogenic.

OMIM ResearchSummary from RefSeq, UniProt

Enables ubiquitin-like ligase-substrate adaptor activity. Involved in ubiquitin-dependent protein catabolic process via the C-end degron rule pathway. Located in nucleoplasm. Part of Cul2-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Gene-disease validity (ClinGen)

neurodevelopmental disorder · ADLimitednot for standalone diagnostic reporting

Interpreting a novel variant

A dominant-negative effect is the curated mechanism (Gene2Phenotype), so a variant that simply removes the protein may not be the pathogenic class here — missense variants in functional domains often carry more weight.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.48

LOEUF

Mechanism· G2P