SPINK2 (serine peptidase inhibitor Kazal type 2)

Gene

• Entrez ID: 6691
• Gene name: Serine peptidase inhibitor Kazal type 2
• Gene symbol: SPINK2
• Synonyms (NCBI Gene): HUSI-II, SPGF29
• Chromosome: 4
• Chromosome location: 4q12
• Summary: This gene encodes a member of the family of serine protease inhibitors of the Kazal type (SPINK). The encoded protein acts as a trypsin and acrosin inhibitor in the genital tract and is localized in the spermatozoa. The protein has been associated with th

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs577163578	G>A,C	Pathogenic	Intron variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1384450	hsa-miR-346	CLIP-seq
MIRT1384451	hsa-miR-4727-5p	CLIP-seq
MIRT1384452	hsa-miR-4769-3p	CLIP-seq
MIRT1384453	hsa-miR-554	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001669	Component	Acrosomal vesicle	IBA
GO:0001669	Component	Acrosomal vesicle	IDA	28554943
GO:0001669	Component	Acrosomal vesicle	IEA
GO:0001675	Process	Acrosome assembly	ISS
GO:0004866	Function	Endopeptidase inhibitor activity	TAS	8428671
GO:0004867	Function	Serine-type endopeptidase inhibitor activity	IEA
GO:0005515	Function	Protein binding	IPI	25416956, 31391482, 31886233, 32814053
GO:0005576	Component	Extracellular region	IEA
GO:0007286	Process	Spermatid development	IBA
GO:0007286	Process	Spermatid development	IEA
GO:0007286	Process	Spermatid development	IMP	28554943
GO:0030414	Function	Peptidase inhibitor activity	IEA
GO:0031410	Component	Cytoplasmic vesicle	IEA

Other IDs

• MIM: 605753
• HGNC: 11245
• e!Ensembl: ENSG00000128040

Protein

• UniProt ID: P20155
• Protein name: Serine protease inhibitor Kazal-type 2 (Acrosin-trypsin inhibitor) (Epididymis tissue protein Li 172) (HUSI-II)
• Protein function: As a strong inhibitor of acrosin, it is required for normal spermiogenesis. It probably hinders premature activation of proacrosin and other proteases, thus preventing the cascade of events leading to spermiogenesis defects (PubMed:28554943). Ma
• PDB: 2JXD, 6KBR
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00050	Kazal_1	36 → 84	Kazal-type serine protease inhibitor domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed in epididymis (at protein level). {ECO:0000269|PubMed:20736409}.
• Sequence:

  MALSVLRLALLLLAVTFAASLIPQFGLFSKYRTPNCSQYRLPGCPRHFNPVCGSDMSTYA
  NECTLCMKIREGGHNIKIIRNGPC

• Sequence length: 84

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
Spermatogenic failure 29	Pathogenic	rs577163578	RCV000677625	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
CORONARY ARTERY DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MAJOR DEPRESSIVE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MALE INFERTILITY WITH AZOOSPERMIA OR OLIGOZOOSPERMIA DUE TO SINGLE GENE MUTATION	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MIGRAINE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPINK2-related disorder	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
STROKE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Relationship Type	References	Evidence Score
Leukemia Myeloid Acute	Associate	37298647, 39506790	★☆☆☆☆ Found in Text Mining only
Lymphoma B Cell	Associate	15308563	★☆☆☆☆ Found in Text Mining only
Lymphoma T Cell Cutaneous	Stimulate	15308563	★☆☆☆☆ Found in Text Mining only
Testicular Neoplasms	Associate	31886233	★☆☆☆☆ Found in Text Mining only