HASPIN

Chr 17

histone H3 associated protein kinase

Also known as: GSG2

NCBI Gene: 83903ENSG00000177602UniProt: Q8TF76

Enables ATP binding activity and histone H3T3 kinase activity. Involved in several processes, including mitotic sister chromatid cohesion; mitotic spindle assembly checkpoint signaling; and protein localization to chromosome, centromeric region. Located in centrosome; nucleoplasm; and spindle. [provided by Alliance of Genome Resources, Jul 2025]

194
ClinVar variants
32
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— HASPIN
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
32 Pathogenic / Likely Pathogenic· 147 VUS of 194 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.
1.01LOEUF
pLI 0.000
Z-score 1.53
OE 0.63 (0.41–1.01)
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.
0.66Z-score
OE missense 0.91 (0.84–0.99)
412 obs / 451.2 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.0.63 (0.41–1.01)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.91 (0.84–0.99)
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.1.04
0≤1.21.6
LoF obs/exp: 13 / 20.5Missense obs/exp: 412 / 451.2Syn Z: -0.43

ClinVar Variant Classifications

194 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic1
VUS147
Likely Benign14
Conflicting1
31
Pathogenic
1
Likely Pathogenic
147
VUS
14
Likely Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
31
0
31
Likely Pathogenic
0
0
1
0
1
VUS
0
130
17
0
147
Likely Benign
0
11
3
0
14
Benign
0
0
0
0
0
Conflicting
—1
Total0141520194

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

View in ClinVar →

Protein Context — Lollipop Plot

HASPIN · 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
Roles and regulation of Haspin kinase and its impact on carcinogenesis.
Quadri R et al.·Cell Signal
2022Review
Nuclear functions regulated by the VRK1 kinase.
Lazo PA·Nucleus
2024Review
Co-inhibition of Aurora A and Haspin kinases enhances survivin blockage and p53 induction for mitotic catastrophe and apoptosis in human colorectal cancer.
Lin CI et al.·Biochem Pharmacol
2022
Modulation of the chromatin phosphoproteome by the Haspin protein kinase.
Maiolica A et al.·Mol Cell Proteomics
2014
Exploring the thermodynamic, kinetic and inhibitory mechanisms of 5-iTU targeting mitotic kinase haspin by integrated molecular dynamics.
Wang Q et al.·Phys Chem Chem Phys
2021Functional
Genome-wide CRISPR screen uncovers a synergistic effect of combining Haspin and Aurora kinase B inhibition.
Huang M et al.·Oncogene
2020
CRISPR/Cas9 screening identifies a kinetochore-microtubule dependent mechanism for Aurora-A inhibitor resistance in breast cancer.
Chen A et al.·Cancer Commun (Lond)
2021Functional
TH2A is phosphorylated at meiotic centromere by Haspin.
Hada M et al.·Chromosoma
2017
OTSSP167 Abrogates Mitotic Checkpoint through Inhibiting Multiple Mitotic Kinases.
Ji W et al.·PLoS One
2016
Antitumor activity of a small-molecule inhibitor of the histone kinase Haspin.
Huertas D et al.·Oncogene
2012
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