SERPINB6

serpin family B member 6, the group of Serpin peptidase inhibitors

Basic information

Region (hg38): 6:2948158-2972165

Previous symbols: [ "PI6", "DFNB91" ]

Links

ENSG00000124570 ∙ NCBI:5269 ∙ OMIM:173321 ∙ HGNC:8950 ∙ Uniprot:P35237 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
• nonsyndromic genetic hearing loss (Moderate), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 91 (Strong), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 91 (Limited), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 91 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal recessive 91	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Audiologic/Otolaryngologic	20451170; 24963352

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SERPINB6 gene.

• not provided (118 variants)
• not specified (40 variants)
• Inborn genetic diseases (13 variants)
• Autosomal recessive nonsyndromic hearing loss 91 (10 variants)
• Usher syndrome (1 variants)
• Hearing impairment (1 variants)
• Rare genetic deafness (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SERPINB6 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				22	2	24
missense			40	7	4	51
nonsense		1				1
start loss		1				1
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			2	25	30	57
Total	0	2	42	54	36

Variants in SERPINB6

This is a list of pathogenic ClinVar variants found in the SERPINB6 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-2948301-C-T		not specified	Likely benign (Aug 11, 2014)
6-2948314-C-T			Uncertain significance (Jun 13, 2022)
6-2948317-C-A		not specified	Uncertain significance (Jul 05, 2022)
6-2948319-G-A			Likely benign (Dec 28, 2023)
6-2948332-C-T			Uncertain significance (Oct 28, 2022)
6-2948333-C-T		Autosomal recessive nonsyndromic hearing loss 91	Uncertain significance (Jun 02, 2022)
6-2948334-G-A		not specified • SERPINB6-related disorder	Benign/Likely benign (Nov 06, 2023)
6-2948337-G-T		not specified	Likely benign (Feb 17, 2021)
6-2948347-T-C			Uncertain significance (May 12, 2022)
6-2948376-G-A			Likely benign (Mar 31, 2023)
6-2948379-G-A		not specified	Likely benign (Mar 23, 2021)
6-2948385-G-A			Likely benign (Nov 10, 2023)
6-2948387-G-A		not specified	Uncertain significance (Sep 14, 2022)
6-2948393-C-T		not specified	Benign (Dec 28, 2023)
6-2948407-C-T			Uncertain significance (Feb 05, 2022)
6-2948432-C-T			Uncertain significance (Apr 22, 2022)
6-2948433-G-A		not specified	Benign/Likely benign (Dec 06, 2022)
6-2948446-G-A			Uncertain significance (Jan 18, 2024)
6-2948469-A-C		not specified	Uncertain significance (Dec 08, 2023)
6-2948483-C-T		not specified	Uncertain significance (Mar 20, 2022)
6-2948488-T-C		not specified	Likely benign (Jul 20, 2015)
6-2948528-C-T		not specified	Uncertain significance (Dec 28, 2022)
6-2948548-G-T			Uncertain significance (Jan 30, 2020)
6-2948556-C-T			Uncertain significance (Feb 24, 2021)
6-2948562-C-T			Likely benign (Apr 07, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SERPINB6	protein_coding	protein_coding	ENST00000380520	6	23698

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000110	0.834	125714	0	34	125748	0.000135

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0613	214	217	0.988	0.0000130	2528
Missense in Polyphen		56	69.793	0.80237		902
Synonymous	-0.522	92	85.8	1.07	0.00000613	689
Loss of Function	1.27	8	12.9	0.618	5.61e-7	172

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000560	0.000560
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000217	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.0000967	0.0000967
Middle Eastern	0.000217	0.000217
South Asian	0.0000327	0.0000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May be involved in the regulation of serine proteinases present in the brain or extravasated from the blood (By similarity). Inhibitor of cathepsin G, kallikrein-8 and thrombin. May play an important role in the inner ear in the protection against leakage of lysosomal content during stress and loss of this protection results in cell death and sensorineural hearing loss. {ECO:0000250, ECO:0000269|PubMed:10068683, ECO:0000269|PubMed:17761692, ECO:0000269|PubMed:20451170, ECO:0000269|PubMed:8136380, ECO:0000269|PubMed:8415716}.
• Pathway: Amoebiasis - Homo sapiens (human);Ectoderm Differentiation;Neutrophil degranulation;Dissolution of Fibrin Clot;Innate Immune System;Immune System;Hemostasis (Consensus)

Intolerance Scores

• loftool: 0.186
• rvis_EVS: -0.14
• rvis_percentile_EVS: 43.77

Haploinsufficiency Scores

• pHI: 0.585
• hipred: N
• hipred_score: 0.247
• ghis: 0.499

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.494

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Serpinb6e

Gene ontology

• Biological process: sensory perception of sound;negative regulation of endopeptidase activity;neutrophil degranulation;cellular response to osmotic stress
• Cellular component: extracellular region;extracellular space;nucleus;cytoplasm;cytosol;plasma membrane;secretory granule membrane;collagen-containing extracellular matrix;extracellular exosome;tertiary granule membrane;serine protease inhibitor complex;ficolin-1-rich granule membrane
• Molecular function: protease binding;serine-type endopeptidase inhibitor activity