LATS2

Chr 13

large tumor suppressor kinase 2

Also known as: KPM

NCBI Gene: 26524 ENSG00000150457 UniProt: Q9NRM7 OMIM: 604861

This gene encodes a serine/threonine kinase that functions as a negative regulator of YAP1 in the Hippo signaling pathway, controlling organ size and tumor suppression by restricting cell proliferation and promoting apoptosis, and also plays critical roles in centrosome duplication and maintaining genomic stability. The gene is highly constrained against loss-of-function variation (pLI=0.99, LOEUF=0.30), but no established Mendelian diseases have been definitively linked to LATS2 mutations in current databases.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a serine/threonine protein kinase belonging to the LATS tumor suppressor family. The protein localizes to centrosomes during interphase, and early and late metaphase. It interacts with the centrosomal proteins aurora-A and ajuba and is required for accumulation of gamma-tubulin and spindle formation at the onset of mitosis. It also interacts with a negative regulator of p53 and may function in a positive feedback loop with p53 that responds to cytoskeleton damage. Additionally, it can function as a co-repressor of androgen-responsive gene expression. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.30

Clinical Summary— LATS2

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 133 VUS of 166 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.30LOEUF

pLI 0.988

Z-score 4.74

OE 0.14 (0.07–0.30)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.21Z-score

OE missense 0.76 (0.70–0.82)

499 obs / 658.8 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.14 (0.07–0.30)

0≤0.351.4

Missense OE?0.76 (0.70–0.82)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 5 / 35.4Missense obs/exp: 499 / 658.8Syn Z: 0.86

This gene — mechanism propensity

0.4388th %ile

GOF

0.4875th %ile

LOF

0.70top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.30

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

166 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1

VUS133

Likely Benign12

Benign13

Likely Pathogenic

133

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	1	0	0	0	1
VUS	0	133	0	0	133
Likely Benign	0	7	0	5	12
Benign	0	4	1	8	13
Total	1	144	1	13	159

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

View in ClinVar →

46 pathogenic / likely-pathogenic (of 59) ClinVar copy-number / structural variants overlap LATS2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →