LAT

linker for activation of T cells

Basic information

Region (hg38): 16:28984826-28990784

Links

ENSG00000213658 ∙ ∙ OMIM:602354 ∙ HGNC:18874 ∙ Uniprot:O43561 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• severe combined immunodeficiency due to LAT deficiency (Strong), mode of inheritance: AR
• severe combined immunodeficiency due to LAT deficiency (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 52	AR	Allergy/Immunology/Infectious	Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; HSCT has been described	Allergy/Immunology/Infectious	27242165; 27522155

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LAT gene.

• not provided (3 variants)
• Severe combined immunodeficiency due to LAT deficiency (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LAT gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	43	1	46
missense			56	4	2	62
nonsense	1					1
start loss						0
frameshift	3	1				4
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			2	6	2	10
non coding			1	37	8	46
Total	4	1	59	84	11

Highest pathogenic variant AF is 0.0000330

Variants in LAT

This is a list of pathogenic ClinVar variants found in the LAT region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-28984900-C-T			Likely benign (Apr 01, 2022)
16-28984905-T-TG		Severe combined immunodeficiency due to LAT deficiency	Pathogenic (Mar 08, 2018)
16-28984913-G-T		LAT-related disorder	Benign (Sep 01, 2024)
16-28985396-C-T		LAT-related disorder	Likely benign (Apr 25, 2019)
16-28985401-T-C		not specified	Uncertain significance (Jul 08, 2022)
16-28985404-G-A			Benign (Dec 31, 2019)
16-28985436-G-T			Benign (Dec 13, 2023)
16-28985444-C-T			Likely benign (Mar 08, 2023)
16-28985445-G-A		not specified	Uncertain significance (Mar 16, 2024)
16-28985457-C-T			Likely benign (Apr 24, 2023)
16-28985459-G-C			Likely benign (Dec 11, 2023)
16-28985460-C-CT		Severe combined immunodeficiency due to LAT deficiency	Pathogenic (Jun 05, 2017)
16-28985469-A-G			Uncertain significance (Aug 08, 2022)
16-28985477-C-T			Likely benign (Nov 15, 2022)
16-28985482-T-C		not specified	Uncertain significance (Apr 26, 2023)
16-28985483-G-A			Likely benign (Jun 14, 2023)
16-28985488-C-T		not specified	Uncertain significance (Mar 26, 2024)
16-28985490-CTGTG-C			Likely pathogenic (May 21, 2018)
16-28985510-A-G			Likely benign (Jan 04, 2024)
16-28985524-G-C			Likely benign (Oct 19, 2021)
16-28985526-G-T			Likely benign (Oct 07, 2022)
16-28985532-G-GGT			Likely benign (Dec 07, 2022)
16-28985533-G-GT			Likely benign (Aug 15, 2022)
16-28985699-CCT-C			Uncertain significance (Jun 20, 2022)
16-28985702-C-G			Likely benign (Dec 30, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LAT	protein_coding	protein_coding	ENST00000395461	12	5958

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00924	0.989	125725	0	15	125740	0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.628	143	166	0.863	0.0000100	1712
Missense in Polyphen		30	45.599	0.65791		494
Synonymous	0.159	68	69.7	0.976	0.00000467	546
Loss of Function	2.68	7	19.9	0.351	0.00000112	202

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000116	0.000116
Ashkenazi Jewish	0.000205	0.000199
East Asian	0.000220	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.0000265	0.0000264
Middle Eastern	0.000220	0.000217
South Asian	0.0000654	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for TCR (T-cell antigen receptor)- and pre-TCR- mediated signaling, both in mature T-cells and during their development. Involved in FCGR3 (low affinity immunoglobulin gamma Fc region receptor III)-mediated signaling in natural killer cells and FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. Couples activation of these receptors and their associated kinases with distal intracellular events such as mobilization of intracellular calcium stores, PKC activation, MAPK activation or cytoskeletal reorganization through the recruitment of PLCG1, GRB2, GRAP2, and other signaling molecules. {ECO:0000269|PubMed:10072481}.
• Disease: DISEASE: Immunodeficiency 52 (IMD52) [MIM:617514]: An autosomal recessive primary immunodeficiency characterized by T-cell abnormalities, resulting in severe combined immunodeficiency, autoimmune disease, progressive lymphopenia and hypogammaglobulinemia, and lymphoproliferation with splenomegaly. Patients develop severe recurrent infections from infancy. {ECO:0000269|PubMed:27242165, ECO:0000269|PubMed:27522155}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: T cell receptor signaling pathway - Homo sapiens (human);Fc epsilon RI signaling pathway - Homo sapiens (human);Fc gamma R-mediated phagocytosis - Homo sapiens (human);Th17 cell differentiation - Homo sapiens (human);Th1 and Th2 cell differentiation - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);Natural killer cell mediated cytotoxicity - Homo sapiens (human);NF-kappa B signaling pathway - Homo sapiens (human);Fc Epsilon Receptor I Signaling in Mast Cells;T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection;Microglia Pathogen Phagocytosis Pathway;Ras Signaling;T-Cell antigen Receptor (TCR) Signaling Pathway;Signal Transduction;DAP12 signaling;DAP12 interactions;role of mef2d in t-cell apoptosis;ras-independent pathway in nk cell-mediated cytotoxicity;t cell receptor signaling pathway;Generation of second messenger molecules;TCR signaling;CD4 T cell receptor signaling-ERK cascade;FCERI mediated MAPK activation;FCERI mediated Ca+2 mobilization;Fc epsilon receptor (FCERI) signaling;TCR;Innate Immune System;Immune System;Adaptive Immune System;GPVI-mediated activation cascade;Platelet activation, signaling and aggregation;Hemostasis;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;Class I PI3K signaling events;Fc-epsilon receptor I signaling in mast cells;TCR signaling in naïve CD8+ T cells;JNK signaling in the CD4+ TCR pathway;Signaling events mediated by PTP1B;TCR signaling in naïve CD4+ T cells;CD4 T cell receptor signaling-JNK cascade;CD4 T cell receptor signaling-NFkB cascade;CD4 T cell receptor signaling (Consensus)

Intolerance Scores

• loftool: 0.0956
• rvis_EVS: -0.54
• rvis_percentile_EVS: 20.54

Haploinsufficiency Scores

• pHI: 0.151
• hipred: Y
• hipred_score: 0.531
• ghis: 0.539

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.383

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Lat
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; digestive/alimentary phenotype; immune system phenotype; renal/urinary system phenotype; respiratory system phenotype; liver/biliary system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan)

Gene ontology

• Biological process: MAPK cascade;adaptive immune response;lymphocyte homeostasis;inflammatory response;immune response;integrin-mediated signaling pathway;Ras protein signal transduction;positive regulation of signal transduction;gene expression;calcium-mediated signaling;intracellular signal transduction;Fc-epsilon receptor signaling pathway;T cell activation;mast cell degranulation;positive regulation of protein kinase activity;T cell receptor signaling pathway;regulation of T cell activation
• Cellular component: immunological synapse;Golgi apparatus;plasma membrane;cell-cell junction;COP9 signalosome;integral component of membrane;mast cell granule;membrane raft
• Molecular function: SH3/SH2 adaptor activity;Ras guanyl-nucleotide exchange factor activity;protein binding;protein kinase binding