LAT2
protein-codinglinker for activation of T cells family member 2
Gene summary
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]
- WBSCR15
- WBSCR5
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~30.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to LAT2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_032464.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 2 | ||||
| missense | 39 | 7 | 46 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 43 | 7 | 0 | 50 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_115853.2 | 11 | MANE Select | |
| Ensembl | ENSP00000420494.1 | 11 | MANE Select | |
| RefSeq | NP_054865.2 | 11 | Standard | |
| RefSeq | NP_115852.1 | 11 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- B Cell Receptor Signaling Pathway
- Fc epsilon receptor (FCERI) signaling
- Innate Immune System
- Immune System
- BCR
Biological Process
- adaptive immune response
- calcium-mediated signaling
- intracellular signal transduction
- Fc-epsilon receptor signaling pathway
- B cell activation
Molecular Function
- protein binding
- SH2 domain binding
Cellular Component
- plasma membrane
- integral component of membrane
- mast cell granule
- membrane raft
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000460943
- Coding exons
- 11
- Length
- 30180
- Individuals with no LoFs
- 124770
- Homozygous LoFs
- 2
- Heterozygous LoFs
- 26
- Defined
- 124798
- p
- 0.000112
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0248 | 145 | 144 | 1.01 | 0.00000835 | 1553 |
| Missense (PolyPhen) | 41 | 44.397 | 0.92348 | 519 | ||
| Synonymous | 1.39 | 47 | 60.8 | 0.774 | 0.00000398 | 459 |
| Loss of Function | 2.09 | 9 | 18.8 | 0.479 | 7.99e-7 | 220 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000074 | 0.000065 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00019 | 0.00018 | rare |
| South Asian | 0.00020 | 0.00016 | rare |
| Other | 0.00034 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. May also be involved in BCR (B-cell antigen receptor)-mediated signaling in B-cells and FCGR1 (high affinity immunoglobulin gamma Fc receptor I)-mediated signaling in myeloid cells. Couples activation of these receptors and their associated kinases with distal intracellular events through the recruitment of GRB2. {ECO:0000269|PubMed:12486104, ECO:0000269|PubMed:12514734, ECO:0000269|PubMed:15010370}.;
- Disease
- DISEASE: Note=LAT2 is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region. Haploinsufficiency of LAT2 may be the cause of certain cardiovascular and musculo-skeletal abnormalities observed in the disease. {ECO:0000269|PubMed:11003705, ECO:0000269|PubMed:11124535, ECO:0000269|Ref.5}.;
Recessive Scores
- pRec
- 0.0928
Intolerance Scores
- LoFtool
- 0.629
- RVIS EVS
- 0.08
- RVIS percentile EVS
- 60.09
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.517
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |