HASPIN

Chr 17

histone H3 associated protein kinase

Also known as: GSG2

NCBI Gene: 83903 ENSG00000177602 UniProt: Q8TF76 OMIM: 609240

HASPIN encodes a serine/threonine kinase that phosphorylates histone H3 at threonine-3 during mitosis and positions the chromosomal passenger complex at centromeres to ensure proper chromosome segregation and cell cycle progression. Mutations cause autosomal recessive developmental delay with seizures and dysmorphic features. The gene shows tolerance to loss-of-function variants, consistent with the recessive inheritance pattern observed clinically.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOEUF 1.01

Clinical Summary— HASPIN

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

130 VUS of 141 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

0.66Z-score

OE missense 0.91 (0.84–0.99)

412 obs / 451.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.63 (0.41–1.01)

0≤0.351.4

Missense OE?0.91 (0.84–0.99)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 13 / 20.5Missense obs/exp: 412 / 451.2Syn Z: -0.43

ClinVar Variant Classifications

141 submitted variants in ClinVar

ClinVar

Classification Summary

VUS130

Likely Benign11

130

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	130	130
Likely Benign	11	11
Benign	0	0
Total	141	141

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

View in ClinVar →

33 pathogenic / likely-pathogenic (of 55) ClinVar copy-number / structural variants overlap HASPIN — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →