SPINK4

Chr 9

serine peptidase inhibitor Kazal type 4

The protein is predicted to function as a serine-type endopeptidase inhibitor in the extracellular region. Currently, no established human diseases have been definitively linked to SPINK4 mutations in clinical practice. The gene shows tolerance to loss-of-function variants with a low constraint score (pLI 0.30, LOEUF 1.19).

OMIMResearchSummary from RefSeq
MultiplemechanismLOEUF 1.19
Clinical SummarySPINK4
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.19LOEUF
pLI 0.296
Z-score 1.37
OE 0.25 (0.091.19)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.34Z-score
OE missense 0.86 (0.671.12)
41 obs / 47.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.25 (0.091.19)
00.351.4
Missense OE0.86 (0.671.12)
00.61.4
Synonymous OE0.75
01.21.6
LoF obs/exp: 1 / 3.9Missense obs/exp: 41 / 47.6Syn Z: 0.84
DN
0.90top 5%
GOF
0.6540th %ile
LOF
0.09100th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SPINK4 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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