SPINK2

serine peptidase inhibitor Kazal type 2, the group of Serine peptidase inhibitors, Kazal type

Basic information

Region (hg38): 4:56809860-56821742

Links

ENSG00000128040 ∙ NCBI:6691 ∙ OMIM:605753 ∙ HGNC:11245 ∙ Uniprot:P20155 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spermatogenic failure 29 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spermatogenic failure 29	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	Genitourinary	28554943

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SPINK2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SPINK2 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					1	1
missense			5		2	7
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1	1		2
non coding				1	1	2
Total	0	0	5	1	4

Variants in SPINK2

This is a list of pathogenic ClinVar variants found in the SPINK2 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-56809985-C-CT		SPINK2-related disorder	Benign (May 01, 2019)
4-56810187-G-A		Spermatogenic failure 29	Uncertain significance (Jan 22, 2020)
4-56811703-G-A		not specified	Uncertain significance (Oct 29, 2021)
4-56820537-G-A		not specified	Uncertain significance (Dec 20, 2023)
4-56820538-T-C		not specified	Uncertain significance (May 09, 2023)
4-56820569-G-A		SPINK2-related disorder	Benign (Aug 13, 2019)
4-56820570-A-C		not specified	Uncertain significance (Mar 24, 2023)
4-56820582-G-C		Spermatogenic failure 29	Pathogenic (Aug 31, 2018)
4-56821450-TC-T		SPINK2-related disorder	Likely benign (Jul 03, 2019)
4-56821545-T-C		SPINK2-related disorder	Benign (Oct 24, 2019)
4-56821553-C-T		SPINK2-related disorder	Benign (Oct 24, 2019)
4-56821611-C-T		not specified	Uncertain significance (Nov 03, 2022)
4-56821634-A-C		not specified	Uncertain significance (Jun 02, 2024)
4-56821669-C-G		SPINK2-related disorder	Likely benign (Jul 03, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SPINK2	protein_coding	protein_coding	ENST00000248701	4	11883

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0698	0.752	119233	0	1	119234	0.00000419

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.663	30	42.1	0.712	0.00000196	524
Missense in Polyphen		7	13.73	0.50985		175
Synonymous	0.357	14	15.8	0.886	6.88e-7	165
Loss of Function	0.931	2	4.01	0.498	1.68e-7	54

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000945	0.00000945
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Strong inhibitor of acrosin in male and/or female genital tract. Also inhibits trypsin. {ECO:0000269|PubMed:19422058}.

Intolerance Scores

• rvis_EVS: 0.01
• rvis_percentile_EVS: 54.63

Haploinsufficiency Scores

• pHI: 0.133
• hipred: N
• hipred_score: 0.173
• ghis: 0.534

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Spink2
• Phenotype: reproductive system phenotype; cellular phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: acrosome assembly;spermatogenesis;spermatid development;negative regulation of serine-type endopeptidase activity
• Cellular component: acrosomal vesicle;extracellular region
• Molecular function: endopeptidase inhibitor activity;serine-type endopeptidase inhibitor activity;protein binding