GPSM2

Chr 1

G protein signaling modulator 2

Also known as: CMCS, DFNB82, LGN, PINS

NCBI Gene: 29899 ENSG00000121957 UniProt: P81274

The encoded protein regulates G protein signaling and organizes mitotic spindle poles, playing essential roles in cell division and asymmetric neuroblast divisions. Mutations cause Chudley-McCullough syndrome, an autosomal recessive disorder characterized by sensorineural hearing loss and brain malformations. This gene shows very low constraint against loss-of-function variants (pLI near zero), consistent with its recessive inheritance pattern where heterozygous carriers are typically unaffected.

ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene belongs to a family of proteins that modulate activation of G proteins, which transduce extracellular signals received by cell surface receptors into integrated cellular responses. The N-terminal half of this protein contains 10 copies of leu-gly-asn (LGN) repeat, and the C-terminal half contains 4 GoLoco motifs, which are involved in guanine nucleotide exchange. This protein may play a role in neuroblast division and in the development of normal hearing. Mutations in this gene are associated with autosomal recessive nonsyndromic deafness (DFNB82). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtChudley-McCullough syndrome

Clinical highlights

Gene-disease validity (ClinGen)

Chudley-McCullough syndrome · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.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

0.86

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

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