GPHN

Chr 14

gephyrin

Also known as: GEPH, GPH, GPHRYN, HKPX1, MOCODC

NCBI Gene: 10243 ENSG00000171723 UniProt: Q9NQX3

The protein anchors inhibitory glycine and GABA-A receptors to postsynaptic microtubules at inhibitory synapses and is required for molybdenum cofactor biosynthesis in non-neuronal tissues. Autosomal recessive loss-of-function mutations cause molybdenum cofactor deficiency type C and may be associated with hyperekplexia. The gene is highly intolerant to loss-of-function variants (pLI 0.999981), consistent with severe disease when both alleles are affected.

ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a neuronal assembly protein that anchors inhibitory neurotransmitter receptors to the postsynaptic cytoskeleton via high affinity binding to a receptor subunit domain and tubulin dimers. In nonneuronal tissues, the encoded protein is also required for molybdenum cofactor biosynthesis. Mutations in this gene may be associated with the neurological condition hyperplexia and also lead to molybdenum cofactor deficiency. Numerous alternatively spliced transcript variants encoding different isoforms have been described; however, the full-length nature of all transcript variants is not currently known. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtMolybdenum cofactor deficiency, type C

Clinical highlights

Gene-disease validity (ClinGen)

sulfite oxidase deficiency due to molybdenum cofactor deficiency type C · ARModerateconsider for supplementary testing

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.18

LOEUF· LoF intol.

LOF

Mechanism· G2P

Some data sources returned errors (1)

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