SPINK4

Chr 9

serine peptidase inhibitor Kazal type 4

Also known as: HEL136, PEC-60, PEC60

NCBI Gene: 27290ENSG00000122711UniProt: O60575

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

103
ClinVar variants
68
Pathogenic / LP
0.30
pLI score
0
Active trials
Clinical Summary— SPINK4
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.
📋
ClinVar Variants
68 Pathogenic / Likely Pathogenic· 32 VUS of 103 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.19LOEUF
pLI 0.296
Z-score 1.37
OE 0.25 (0.09–1.19)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.34Z-score
OE missense 0.86 (0.67–1.12)
41 obs / 47.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.25 (0.09–1.19)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.86 (0.67–1.12)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.75
0≤1.21.6
LoF obs/exp: 1 / 3.9Missense obs/exp: 41 / 47.6Syn Z: 0.84

ClinVar Variant Classifications

103 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic60
Likely Pathogenic8
VUS32
Likely Benign1
Benign1
60
Pathogenic
8
Likely Pathogenic
32
VUS
1
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
60
0
60
Likely Pathogenic
0
0
8
0
8
VUS
0
20
12
0
32
Likely Benign
0
1
0
0
1
Benign
0
0
1
0
1
Total021810102

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Baseline Serum and Stool Microbiome Biomarkers Predict Clinical Efficacy and Tissue Molecular Response After Ritlecitinib Induction Therapy in Ulcerative Colitis.
Hassan-Zahraee M et al.·J Crohns Colitis
2024Clinical trial
Leveraging a KRAS-based signature to predict the prognosis and drug sensitivity of colon cancer and identifying SPINK4 as a new biomarker.
Huo JT et al.·Sci Rep
2023
Downregulated SPINK4 is associated with poor survival in colorectal cancer.
Wang X et al.·BMC Cancer
2019
High SPINK4 Expression Predicts Poor Outcomes among Rectal Cancer Patients Receiving CCRT.
Chen TJ et al.·Curr Oncol
2021Cohort
Single-cell profiling reveals differences between human classical adenocarcinoma and mucinous adenocarcinoma.
Hu FJ et al.·Commun Biol
2023
[Identification of potential pathogenic genes of intestinal metaplasia based on transcriptomic sequencing and bioinformatics analysis].
Pei B et al.·Nan Fang Yi Ke Da Xue Xue Bao
2024
Immunopathology of childhood celiac disease-Key role of intestinal epithelial cells.
Pietz G et al.·PLoS One
2017
Identification of Prognosis-Related Genes in Bladder Cancer Microenvironment across TCGA Database.
Zhao X et al.·Biomed Res Int
2020
Single cell RNA-seq reveals profound transcriptional similarity between Barrett's oesophagus and oesophageal submucosal glands.
Owen RP et al.·Nat Commun
2018
Multiplex Proteomics in the Identification of Potential Biomarkers of Very Severe Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease in Allogeneic Hematopoietic Cell Transplant Patients Treated with Defibrotide.
Vasudevan Nampoothiri R et al.·Acta Haematol
2024Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools