SERPINB6 (serpin family B member 6)

Gene

• Entrez ID: 5269
• Gene name: Serpin family B member 6
• Gene symbol: SERPINB6
• Synonyms (NCBI Gene): CAP, DFNB91, MSTP057, PI-6, PI6, PTI, SPI3
• Chromosome: 6
• Chromosome location: 6p25.2
• Summary: 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 ha

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs267607037	C>A	Pathogenic	Coding sequence variant, stop gained, non coding transcript variant
rs1201327476	C>A,T	Likely-pathogenic	Coding sequence variant, non coding transcript variant, missense variant, stop gained

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT002646	hsa-miR-124-3p	Microarray	18668037
MIRT002646	hsa-miR-124-3p	Microarray	15685193
MIRT439676	hsa-miR-218-5p	HITS-CLIP	23212916
MIRT439676	hsa-miR-218-5p	HITS-CLIP	23212916
MIRT1338699	hsa-miR-122	CLIP-seq
MIRT1338700	hsa-miR-3177-3p	CLIP-seq
MIRT1338701	hsa-miR-3614-5p	CLIP-seq
MIRT1338702	hsa-miR-3940-5p	CLIP-seq
MIRT1338703	hsa-miR-4269	CLIP-seq
MIRT1338704	hsa-miR-4318	CLIP-seq
MIRT1338705	hsa-miR-4507	CLIP-seq
MIRT1338706	hsa-miR-4715-3p	CLIP-seq
MIRT1338707	hsa-miR-4717-5p	CLIP-seq
MIRT1338708	hsa-miR-4753-5p	CLIP-seq
MIRT1338699	hsa-miR-122	CLIP-seq
MIRT1338700	hsa-miR-3177-3p	CLIP-seq
MIRT1338701	hsa-miR-3614-5p	CLIP-seq
MIRT1338702	hsa-miR-3940-5p	CLIP-seq
MIRT1338703	hsa-miR-4269	CLIP-seq
MIRT1338704	hsa-miR-4318	CLIP-seq
MIRT1338705	hsa-miR-4507	CLIP-seq
MIRT1338706	hsa-miR-4715-3p	CLIP-seq
MIRT1338707	hsa-miR-4717-5p	CLIP-seq
MIRT1338708	hsa-miR-4753-5p	CLIP-seq
MIRT1338700	hsa-miR-3177-3p	CLIP-seq
MIRT1338701	hsa-miR-3614-5p	CLIP-seq
MIRT1338702	hsa-miR-3940-5p	CLIP-seq
MIRT1338703	hsa-miR-4269	CLIP-seq
MIRT1338704	hsa-miR-4318	CLIP-seq
MIRT1338705	hsa-miR-4507	CLIP-seq
MIRT1338706	hsa-miR-4715-3p	CLIP-seq
MIRT1338707	hsa-miR-4717-5p	CLIP-seq
MIRT1338708	hsa-miR-4753-5p	CLIP-seq
MIRT1338699	hsa-miR-122	CLIP-seq
MIRT1338700	hsa-miR-3177-3p	CLIP-seq
MIRT1338701	hsa-miR-3614-5p	CLIP-seq
MIRT1338702	hsa-miR-3940-5p	CLIP-seq
MIRT1338703	hsa-miR-4269	CLIP-seq
MIRT1338704	hsa-miR-4318	CLIP-seq
MIRT1338705	hsa-miR-4507	CLIP-seq
MIRT1338706	hsa-miR-4715-3p	CLIP-seq
MIRT1338707	hsa-miR-4717-5p	CLIP-seq
MIRT1338708	hsa-miR-4753-5p	CLIP-seq
MIRT1338699	hsa-miR-122	CLIP-seq
MIRT2690481	hsa-miR-3150b-3p	CLIP-seq
MIRT1338700	hsa-miR-3177-3p	CLIP-seq
MIRT2690482	hsa-miR-3184	CLIP-seq
MIRT1338701	hsa-miR-3614-5p	CLIP-seq
MIRT1338702	hsa-miR-3940-5p	CLIP-seq
MIRT2690483	hsa-miR-423-5p	CLIP-seq
MIRT1338703	hsa-miR-4269	CLIP-seq
MIRT1338704	hsa-miR-4318	CLIP-seq
MIRT1338705	hsa-miR-4507	CLIP-seq
MIRT1338706	hsa-miR-4715-3p	CLIP-seq
MIRT1338707	hsa-miR-4717-5p	CLIP-seq
MIRT1338708	hsa-miR-4753-5p	CLIP-seq
MIRT2690484	hsa-miR-4784	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0002020	Function	Protease binding	IPI	14670919, 17761692
GO:0004867	Function	Serine-type endopeptidase inhibitor activity	IBA
GO:0004867	Function	Serine-type endopeptidase inhibitor activity	IDA	17761692
GO:0004867	Function	Serine-type endopeptidase inhibitor activity	IEA
GO:0004867	Function	Serine-type endopeptidase inhibitor activity	TAS	8415716
GO:0005576	Component	Extracellular region	HDA	27068509
GO:0005615	Component	Extracellular space	IBA
GO:0005615	Component	Extracellular space	IEA
GO:0005634	Component	Nucleus	IDA	14670919
GO:0005737	Component	Cytoplasm	IBA
GO:0005737	Component	Cytoplasm	IDA	14670919, 17761692, 20451170
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	TAS	8415716
GO:0005886	Component	Plasma membrane	TAS
GO:0007605	Process	Sensory perception of sound	IMP	20451170
GO:0030414	Function	Peptidase inhibitor activity	IEA
GO:0030667	Component	Secretory granule membrane	TAS
GO:0031012	Component	Extracellular matrix	HDA	28344315, 28675934
GO:0070062	Component	Extracellular exosome	HDA	19056867, 23533145
GO:0070821	Component	Tertiary granule membrane	TAS
GO:0071470	Process	Cellular response to osmotic stress	IMP	20451170
GO:0097180	Component	Serine protease inhibitor complex	IDA	17761692
GO:0101003	Component	Ficolin-1-rich granule membrane	TAS

Other IDs

• MIM: 173321
• HGNC: 8950
• e!Ensembl: ENSG00000124570

Protein

• UniProt ID: P35237
• Protein name: Serpin B6 (Cytoplasmic antiproteinase) (CAP) (Peptidase inhibitor 6) (PI-6) (Placental thrombin inhibitor)
• Protein 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 again
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00079	Serpin	6 → 376	Serpin (serine protease inhibitor)	Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed in keratinocytes (at protein level). Highest levels in skeletal muscle. Also found in placenta, cardiac muscle, lung, liver, kidney and pancreas. Expressed in the inner ear hair cells. Expressed abundantly by normal mast cell
• Sequence:

  MDVLAEANGTFALNLLKTLGKDNSKNVFFSPMSMSCALAMVYMGAKGNTAAQMAQILSFN
  KSGGGGDIHQGFQSLLTEVNKTGTQYLLRMANRLFGEKSCDFLSSFRDSCQKFYQAEMEE
  LDFISAVEKSRKHINTWVAEKTEGKIAELLSPGSVDPLTRLVLVNAVYFRGNWDEQFDKE
  NTEERLFKVSKNEEKPVQMMFKQSTFKKTYIGEIFTQILVLPYVGKELNMIIMLPDETTD
  LRTVEKELTYEKFVEWTRLDMMDEEEVEVSLPRFKLEESYDMESVLRNLGMTDAFELGKA
  DFSGMSQTDLSLSKVVHKSFVEVNEEGTEAAAATAAIMMMRCARFVPRFCADHPFLFFIQ
  HSKTNGILFCGRFSSP

• Sequence length: 376

Pathways

KEGG:

Amoebiasis

Reactome:

Neutrophil degranulation
Dissolution of Fibrin Clot

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Autosomal recessive nonsyndromic hearing loss 91	Likely pathogenic; Pathogenic	rs1225963332, rs267607037	RCV001783729 RCV000014571	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Melanoma	Likely pathogenic	rs1201327476	RCV005898778	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Rare genetic deafness	Likely pathogenic	rs1201327476	RCV000601975	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
AUTOSOMAL RECESSIVE ISOLATED SENSORINEURAL DEAFNESS TYPE DFNB	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHRONIC LYMPHOCYTIC LEUKEMIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon adenocarcinoma	-	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CROHN'S DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEAFNESS, AUTOSOMAL RECESSIVE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEAFNESS, AUTOSOMAL RECESSIVE 91	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hearing impairment	Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
HEARING LOSS, AUTOSOMAL RECESSIVE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INFLAMMATORY BOWEL DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SENSORINEURAL HEARING LOSS OF BILATERAL EARS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SERPINB6-related disorder	Benign; Likely benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Usher syndrome	Conflicting classifications of pathogenicity	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
VITILIGO	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acute leukemia	Leukemia	BEFREE	29456727		★☆☆☆☆ Found in Text Mining only
Allergic sensitization	Allergic Sensitization	BEFREE	28477791		★☆☆☆☆ Found in Text Mining only
Amyloidosis	Amyloidosis	BEFREE	29967939		★☆☆☆☆ Found in Text Mining only
Amyloidosis	Amyloidosis	Pubtator	29967939	Associate	★☆☆☆☆ Found in Text Mining only
Aplastic Anemia	Aplastic anemia	BEFREE	2624428		★☆☆☆☆ Found in Text Mining only
Asthma	Asthma	BEFREE	22913580		★☆☆☆☆ Found in Text Mining only
Autosomal recessive non-syndromic sensorineural deafness type DFNB	Non-Syndromic Sensorineural Deafness	Orphanet			★☆☆☆☆ Found in Text Mining only
beta Thalassemia	beta Thalassemia	BEFREE	1643026		★☆☆☆☆ Found in Text Mining only
Beta thalassemia intermedia	beta Thalassemia	BEFREE	26418075		★☆☆☆☆ Found in Text Mining only
beta^+^ Thalassemia	beta Thalassemia	BEFREE	1643026		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	19289584, 19369627, 19864236, 24698965, 25367072, 25818873, 26473483, 26754674, 27180259, 27455837, 28764718, 30953146, 31076089, 31732618		★☆☆☆☆ Found in Text Mining only
Carcinoma, Ovarian Epithelial	Ovarian Epithelial carcinoma	BEFREE	25133707		★☆☆☆☆ Found in Text Mining only
Cerebral Infarction	Cerebral Infarction	BEFREE	15082799		★☆☆☆☆ Found in Text Mining only
Cerebrovascular accident	Stroke	BEFREE	15082799, 31806131		★☆☆☆☆ Found in Text Mining only
Chronic Lymphocytic Leukemia	Lymphocytic Leukemia	GWASCAT_DG	26956414		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colitis	Colitis	BEFREE	30144577		★☆☆☆☆ Found in Text Mining only
Congenital chromosomal disease	Congenital Chromosomal Disease	BEFREE	16368518		★☆☆☆☆ Found in Text Mining only
DEAFNESS, AUTOSOMAL RECESSIVE 91	Deafness	GENOMICS_ENGLAND_DG	8614560		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEAFNESS, AUTOSOMAL RECESSIVE 91	Deafness	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEAFNESS, AUTOSOMAL RECESSIVE 91	Deafness	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Diabetes	Diabetes	BEFREE	31612634		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes Mellitus	BEFREE	31612634		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	BEFREE	28225806		★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	BEFREE	31638258		★☆☆☆☆ Found in Text Mining only
Epithelial ovarian cancer	Ovarian cancer	BEFREE	25133707		★☆☆☆☆ Found in Text Mining only
Fatty Liver	Fatty Liver	BEFREE	29108123		★☆☆☆☆ Found in Text Mining only
Fibrosis, Liver	Liver Fibrosis	BEFREE	27639088		★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	BEFREE	28555065		★☆☆☆☆ Found in Text Mining only
Glioblastoma Multiforme	Glioblastoma	BEFREE	28555065		★☆☆☆☆ Found in Text Mining only
Hearing Loss	Hearing loss	Pubtator	20451170, 33997018	Associate	★☆☆☆☆ Found in Text Mining only
Hearing Loss Sensorineural	Hearing loss	Pubtator	20451170, 25719458	Associate	★☆☆☆☆ Found in Text Mining only
Huntington Disease	Huntington Disease	BEFREE	21858921		★☆☆☆☆ Found in Text Mining only
Hypersomnia	Hypersomnia	BEFREE	29631952		★☆☆☆☆ Found in Text Mining only
Lewy Body Disease	Lewy Body Disease	BEFREE	28837937		★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	16368518, 23742296		★☆☆☆☆ Found in Text Mining only
Malignant lymphoma, lymphocytic, intermediate differentiation, diffuse	Malignant lymphoma, lymphocytic, intermediate differentiation	BEFREE	30348538		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	19289584, 19369627, 19864236, 24504069, 25367072, 25818873, 26223814, 26473483, 26754674, 26820945, 27180259, 27455837, 27716627, 28764718, 30520947, 31076089, 31732618		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	BEFREE	28917266		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of stomach	Stomach Neoplasms	BEFREE	29901187		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	24464224, 24551292, 31837433		★☆☆☆☆ Found in Text Mining only
Mammary Neoplasms	Mammary Neoplasms	BEFREE	30241820		★☆☆☆☆ Found in Text Mining only
Mannose-Binding Protein Deficiency	Mannose-Binding Protein Deficiency	BEFREE	22523362		★☆☆☆☆ Found in Text Mining only
Mantle cell lymphoma	Mantle Cell Lymphoma	BEFREE	30348538		★☆☆☆☆ Found in Text Mining only
Mastocytosis	Mastocytosis	BEFREE	14670919		★☆☆☆☆ Found in Text Mining only
Motor neuron atrophy	Motor neuron atrophy	BEFREE	19279216		★☆☆☆☆ Found in Text Mining only
Mouth Diseases	Mouth disease	Pubtator	36216310	Stimulate	★☆☆☆☆ Found in Text Mining only
Muscular Dystrophies, Limb-Girdle	Limb-Girdle Muscular Dystrophy	BEFREE	30564623		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	10440809, 27180259, 28032917, 28192599, 29137411, 30520947, 31375912		★☆☆☆☆ Found in Text Mining only
Non-alcoholic Fatty Liver Disease	Non-Alcoholic Fatty Liver Disease	BEFREE	29108123		★☆☆☆☆ Found in Text Mining only
Nonsyndromic Deafness	Nonsyndromic Deafness	CLINGEN_DG	20451170, 23669344, 25719458		★☆☆☆☆ Found in Text Mining only
Osteosarcoma	Osteosarcoma	BEFREE	30286779		★☆☆☆☆ Found in Text Mining only
Pancreatic Neoplasms	Pancreatic neoplasm	Pubtator	12673124	Associate	★☆☆☆☆ Found in Text Mining only
Paroxysmal nocturnal hemoglobinuria	Paroxysmal nocturnal hemoglobinuria	BEFREE	23402025		★☆☆☆☆ Found in Text Mining only
Perry Syndrome	Perry Syndrome	BEFREE	19136952, 20518521		★☆☆☆☆ Found in Text Mining only
Pleural effusion disorder	Pleural effusion	BEFREE	31774020		★☆☆☆☆ Found in Text Mining only
Prostate carcinoma	Prostate cancer	BEFREE	28917266		★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic Neoplasms	BEFREE	31303963		★☆☆☆☆ Found in Text Mining only
Sensorineural Hearing Loss (disorder)	Hearing Loss	BEFREE	20451170, 25817395		★☆☆☆☆ Found in Text Mining only
Small Lymphocytic Lymphoma	Lymphocytic Leukemia	GWASCAT_DG	26956414		★☆☆☆☆ Found in Text Mining only
Steatohepatitis	Fatty Liver	BEFREE	29108123, 29463916, 31295293, 31377187, 31807383		★☆☆☆☆ Found in Text Mining only
Stomach Carcinoma	Stomach Carcinoma	BEFREE	29901187		★☆☆☆☆ Found in Text Mining only
Thymic Carcinoma	Thymic Carcinoma	BEFREE	30527189		★☆☆☆☆ Found in Text Mining only
Thymoma	Thymoma	BEFREE	30527189		★☆☆☆☆ Found in Text Mining only
Uterine Cervical Neoplasms	Uterine neoplasm	Pubtator	31271297	Associate	★☆☆☆☆ Found in Text Mining only