SERPINB6

Chr 6

serpin family B member 6

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

NCBI Gene: 5269ENSG00000124570UniProt: P35237

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]

Primary Disease Associations & Inheritance

UniProtDeafness, autosomal recessive, 91
0
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SERPINB6
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Gene-Disease Validity (ClinGen)
nonsyndromic genetic hearing loss · ARModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.11LOEUF
pLI 0.000
Z-score 1.27
OE 0.62 (0.36–1.11)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.06Z-score
OE missense 0.99 (0.88–1.11)
214 obs / 216.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.62 (0.36–1.11)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.99 (0.88–1.11)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.07
0≤1.21.6
LoF obs/exp: 8 / 12.9Missense obs/exp: 214 / 216.5Syn Z: -0.52

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

SERPINB6 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

SERPINB6-related deafness

definitive
ARLoss Of FunctionAbsent Gene Product
Ear
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Targeted disruption of SPI3/Serpinb6 does not result in developmental or growth defects, leukocyte dysfunction, or susceptibility to stroke.
Scarff KL et al.·Mol Cell Biol
2004
Genetic Aetiology of Nonsyndromic Hearing Loss in Moravia-Silesia.
Plevova P et al.·Medicina (Kaunas)
2018
Identification of Hearing Loss-Associated Variants of PTPRQ, MYO15A, and SERPINB6 in Pakistani Families.
Mahmood U et al.·Biomed Res Int
2021
Characterization of DNA hydroxymethylation profile in cervical cancer.
Wang J et al.·Artif Cells Nanomed Biotechnol
2019
Amplification of Inflammation by Lubricin Deficiency Implicated in Incident, Erosive Gout Independent of Hyperuricemia.
Elsaid K et al.·Arthritis Rheumatol
2023
Subtelomeric 6p25 deletion/duplication: Report of a patient with new clinical findings and genotype-phenotype correlations.
Linhares ND et al.·Eur J Med Genet
2015Case report
[Colorectal cancer 2D-proteomics: identification of altered protein expression].
Krasnov GS et al.·Mol Biol (Mosk)
2009
In GnRH antagonist/rec-FSH stimulated cycles, advanced endometrial maturation on the day of oocyte retrieval correlates with altered gene expression.
Van Vaerenbergh I et al.·Hum Reprod
2009
Whole-exome sequencing reveals diverse modes of inheritance in sporadic mild to moderate sensorineural hearing loss in a pediatric population.
Kim NK et al.·Genet Med
2015
Screening of 38 genes identifies mutations in 62% of families with nonsyndromic deafness in Turkey.
Duman D et al.·Genet Test Mol Biomarkers
2011
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools