SPINK8

protein-coding

serine peptidase inhibitor Kazal type 8 (putative), the group of MicroRNA protein coding host genes|Serine peptidase inhibitors, Kazal type

Gene summary

Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001080525.3

Inheritance

—

ClinVar variants

U:8

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.1

Max pathogenic AF

—

Genomic locus

chr3:48,306,842-48,333,661

External References & Databases

Ensembl (ENSG00000229453)

Transcript & Mutation Effects

hg38 • Region Span ~26.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SPINK8 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 8

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001080525.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			8 clinvar			8
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	8	0	0	8

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 11 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001080525.3	RefSeq	NP_001073994.1	5	MANE Select
ENST00000434006.3	Ensembl	ENSP00000407497.1	5	MANE Select
ENST00000944525.1	Ensembl	ENSP00000614584.1	6	Standard
ENST00000944525.2	Ensembl	ENSP00000614584.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of endopeptidase activity

Molecular Function

serine-type endopeptidase inhibitor activity

Cellular Component

extracellular region

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000434006
Coding exons: 5
Length: 21496
Individuals with no LoFs: 124628
Homozygous LoFs: 0
Heterozygous LoFs: 14
Defined: 124642
p: 0.0000562

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0536	43	44.0	0.977	0.00000194	635
Missense (PolyPhen)		13	10.774	1.2066		153
Synonymous	-0.0283	15	14.9	1.01	7.30e-7	162
Loss of Function	-0.221	6	5.44	1.10	2.29e-7	77

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00013	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000056	0.000056	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000035	0.000035	rare
South Asian	0.00023	0.00023	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probable serine protease inhibitor. {ECO:0000250}.;

Intolerance Scores

RVIS EVS: 0.52
RVIS percentile EVS: 80.46

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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