LAT2

Chr 7

linker for activation of T cells family member 2

Also known as: HSPC046, LAB, NTAL, WBSCR15, WBSCR5, WSCR5

NCBI Gene: 7462 ENSG00000086730 UniProt: Q9GZY6 OMIM: 605719

LAT2 encodes a transmembrane adaptor protein that couples high-affinity immunoglobulin receptors (including IgE receptors in mast cells and IgG receptors in myeloid cells) with downstream signaling cascades through recruitment of GRB2. LAT2 is located in the 7q11.23 region commonly deleted in Williams syndrome, a multisystem developmental disorder affecting cardiovascular, neurodevelopmental, and other organ systems. The gene shows low constraint against loss-of-function variants (pLI 0.0002), and inheritance follows an autosomal dominant pattern when considering Williams syndrome deletions.

OMIM ResearchSummary from RefSeq, UniProt

This gene is one of the contiguous genes at 7q11.23 commonly deleted in Williams syndrome, a multisystem developmental disorder. This gene consists of at least 14 exons, and its alternative splicing generates 3 transcript variants, all encoding the same protein. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

—

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

gnomad: Error: gnomAD API error: 400

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in LAT2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

302 rare PASS variants

Rare truncating (LoF)

1 in 2,900

62 rare PASS variants

Rare synonymous (reference)

1 in 210

137 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for LAT2. 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 210	1 in 3,400
South Asian	~43k	1 in 130	1 in 990
Remaining (unassigned)	~30k	1 in 140	1 in 4,300
European (Finnish)	~27k	1 in 680	≈ 1 in 27,000
Admixed American	~22k	1 in 150	1 in 3,600
African / African American	~21k	1 in 140	≈ 1 in 4,600
East Asian	~20k	1 in 170	1 in 2,100
Ashkenazi Jewish	~13k	≈ 1 in 6,500	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 130	≈ 1 in 1,400

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.