SERPINB6

Chr 6

serpin family B member 6

Also known as: CAP, DFNB91, MSTP057, PI-6, PI6, PTI, SPI3

NCBI Gene: 5269 ENSG00000124570 UniProt: P35237

SERPINB6 encodes a serine protease inhibitor that inhibits cathepsin G, kallikrein-8, and thrombin, and protects inner ear hair cells against lysosomal content leakage during cellular stress. Mutations cause autosomal recessive nonsyndromic progressive sensorineural hearing loss (DFNB91). The gene shows low constraint to loss-of-function variation, consistent with its recessive inheritance pattern.

ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a member of the serpin (serine proteinase inhibitor) superfamily, and ovalbumin(ov)-serpin subfamily. It was originally discovered as a placental thrombin inhibitor. The mouse homolog was found to be expressed in the hair cells of the inner ear. Mutations in this gene are associated with nonsyndromic progressive hearing loss, suggesting that this serpin plays an important role in the inner ear in the protection against leakage of lysosomal content during stress, and that loss of this protection results in cell death and sensorineural hearing loss. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2010]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtDeafness, autosomal recessive, 91

Clinical highlights

Gene-disease validity (ClinGen)

nonsyndromic genetic hearing loss · ARModerateconsider for supplementary testing

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)

—

P/LP submissions

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P/LP missense

1.11

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

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