LATS2

Chr 13

large tumor suppressor kinase 2

Also known as: KPM

NCBI Gene: 26524 ENSG00000150457 UniProt: Q9NRM7

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.

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]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.30

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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

Background carrier burden — how many people carry a rare variant somewhere in LATS2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 39

1,385 rare PASS variants

Rare truncating (LoF)

1 in 1,900

93 rare PASS variants

Rare synonymous (reference)

1 in 41

729 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for LATS2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 50	1 in 2,700
South Asian	~43k	1 in 38	1 in 1,300
Remaining (unassigned)	~30k	1 in 36	1 in 3,500
European (Finnish)	~27k	1 in 200	1 in 360
Admixed American	~22k	1 in 43	1 in 2,500
African / African American	~21k	1 in 43	1 in 3,100
East Asian	~20k	1 in 51	≈ 1 in 5,000
Ashkenazi Jewish	~13k	1 in 410	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 51	≈ 1 in 600

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 6 of 7 coding exons well covered in gnomAD exomes; exon 7 marginal. Genomes: all 7.? see exons ↓