LAX1

Summary

LAX1 (lymphocyte transmembrane adaptor 1, HGNC:26005) is a protein-coding gene on chromosome 1q32.1, encoding Lymphocyte transmembrane adapter 1 (Q8IWV1). Negatively regulates TCR (T-cell antigen receptor)-mediated signaling in T-cells and BCR (B-cell antigen receptor)-mediated signaling in B-cells.

Enables SH2 domain binding activity and protein kinase binding activity. Involved in several processes, including B cell activation; negative regulation of MAPK cascade; and negative regulation of T cell activation. Located in Golgi apparatus; cytosol; and plasma membrane.

Source: NCBI Gene 54900 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 69 total
• MANE Select transcript: NM_017773

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26005
Approved symbol	LAX1
Name	lymphocyte transmembrane adaptor 1
Location	1q32.1
Locus type	gene with protein product
Status	Approved
Aliases	LAX, FLJ20340
Ensembl gene	ENSG00000122188
Ensembl biotype	protein_coding
OMIM	619622
Entrez	54900

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000367215, ENST00000367217, ENST00000442561

RefSeq mRNA: 3 — MANE Select: NM_017773 NM_001136190, NM_001282878, NM_017773

CCDS: CCDS1441, CCDS44297

Canonical transcript exons

ENST00000442561 — 5 exons

Exon	Start	End
ENSE00001128797	203773875	203776372
ENSE00001443848	203765183	203765654
ENSE00003637489	203771367	203771477
ENSE00003663579	203772068	203772147
ENSE00003675910	203770828	203770937

Expression profiles

Bgee: expression breadth ubiquitous, 152 present calls, max score 81.62.

FANTOM5 (CAGE): breadth broad, TPM avg 4.8209 / max 746.8638, expressed in 234 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
7935	4.3796	230
7936	0.1916	45
7937	0.1137	13
7934	0.1087	60
7938	0.0273	6

Top tissues by expression

248 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lymph node	UBERON:0000029	81.62	gold quality
bone marrow cell	CL:0002092	81.60	gold quality
granulocyte	CL:0000094	80.82	gold quality
epithelium of nasopharynx	UBERON:0001951	80.79	gold quality
superficial temporal artery	UBERON:0001614	80.25	gold quality
vermiform appendix	UBERON:0001154	79.29	gold quality
trabecular bone tissue	UBERON:0002483	77.60	silver quality
caecum	UBERON:0001153	76.60	gold quality
blood	UBERON:0000178	75.97	gold quality
tonsil	UBERON:0002372	74.90	gold quality
bone marrow	UBERON:0002371	74.63	gold quality
buccal mucosa cell	CL:0002336	74.20	gold quality
lower lobe of lung	UBERON:0008949	73.32	gold quality
spleen	UBERON:0002106	73.26	gold quality
pleura	UBERON:0000977	72.11	silver quality
parietal pleura	UBERON:0002400	71.80	silver quality
rectum	UBERON:0001052	71.46	gold quality
visceral pleura	UBERON:0002401	71.25	gold quality
colonic epithelium	UBERON:0000397	69.71	silver quality
gall bladder	UBERON:0002110	69.49	gold quality
gingival epithelium	UBERON:0001949	69.10	gold quality
oral cavity	UBERON:0000167	68.79	gold quality
mucosa of sigmoid colon	UBERON:0004993	68.64	silver quality
thymus	UBERON:0002370	67.88	gold quality
jejunal mucosa	UBERON:0000399	67.79	gold quality
upper leg skin	UBERON:0004262	66.71	gold quality
pancreatic ductal cell	CL:0002079	65.98	silver quality
colonic mucosa	UBERON:0000317	65.56	gold quality
duodenum	UBERON:0002114	65.49	gold quality
small intestine Peyer’s patch	UBERON:0003454	64.59	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	18.11
E-MTAB-6386	no	469.19

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

50 targeting LAX1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-9851-3P	99.63	69.68	1110
HSA-MIR-17-3P	99.55	66.77	1311
HSA-MIR-4796-5P	99.34	70.06	810
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-5584-3P	99.23	68.79	1351
HSA-MIR-6744-3P	99.22	64.41	972
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-4757-5P	99.12	64.51	981
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-6506-5P	99.04	65.66	1386
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-6728-3P	98.63	67.63	1534

Literature-anchored findings (GeneRIF, showing 5)

• Overexpression of LAX in Jurkat cells specifically inhibits T cell receptor-mediated p38 MAPK activation and NFAT/AP-1 transcriptional activation. (PMID:12359715)
• functions to negatively regulate signaling in lymphocytes (PMID:12359715)
• inhibition of signaling events involved in T cell activation by LAX occurs through mechanisms both dependent on and independent of its tyrosine phosphorylation. (PMID:18981125)
• We identified the transmembrane domain of LAX as a first motif targeting transmembrane protein constructs to detergent-resistant heavy rafts, a novel type of membrane microdomains containing a number of physiologically important proteins. (PMID:22662118)
• TRIM required LAX for binding to Rab8 in a complex, a novel CTLA-4/TRIM/LAX/Rab8 effector complex in the transport of CTLA-4 to the surfaces of T cells (PMID:24515439)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lax1	ENSMUSG00000051998
rattus_norvegicus	Lax1	ENSRNOG00000028250

Protein

Protein identifiers

Lymphocyte transmembrane adapter 1 — Q8IWV1 (reviewed: Q8IWV1)

Alternative names: Linker for activation of X cells, Membrane-associated adapter protein LAX

All UniProt accessions (1): Q8IWV1

UniProt curated annotations — full annotation on UniProt →

Function. Negatively regulates TCR (T-cell antigen receptor)-mediated signaling in T-cells and BCR (B-cell antigen receptor)-mediated signaling in B-cells.

Subunit / interactions. When phosphorylated, interacts with GRB2, PIK3R1 and GRAP2.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in spleen, thymus, and peripheral blood leukocytes. Expressed in several B-, T-, NK and monocyte cell lines.

Post-translational modifications. Phosphorylated on tyrosines by Syk, Lck or ZAP70 upon TCR or BCR activation; which leads to the recruitment of GRB2, PIK3R1 and GRAP2.

Induction. Up-regulated in T-cells following TCR engagement.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8IWV1-1	1	yes
Q8IWV1-2	2
Q8IWV1-3	3

RefSeq proteins (3): NP_001129662, NP_001269807, NP_060243* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR031393	LAX	Family

Pfam: PF15681

UniProt features (19 total): modified residue 5, sequence conflict 3, region of interest 3, topological domain 2, splice variant 2, compositionally biased region 2, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IWV1-F1	48.35	0.04

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (5): 268, 294, 345, 373, 193

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 142 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_B_CELL_ACTIVATION, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_CELL_CELL_ADHESION, GOBP_NEGATIVE_REGULATION_OF_MAPK_CASCADE, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_CELL_CELL_ADHESION, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOMF_SH2_DOMAIN_BINDING, GOBP_ADAPTIVE_IMMUNE_RESPONSE, GOBP_LEUKOCYTE_CELL_CELL_ADHESION, GOBP_NEGATIVE_REGULATION_OF_CELL_ACTIVATION, MULLIGHAN_NPM1_SIGNATURE_3_DN, GOBP_REGULATION_OF_LYMPHOCYTE_ACTIVATION

GO Biological Process (10): adaptive immune response (GO:0002250), immune response (GO:0006955), intracellular signal transduction (GO:0035556), B cell activation (GO:0042113), negative regulation of MAPK cascade (GO:0043409), lymphocyte activation (GO:0046649), antigen receptor-mediated signaling pathway (GO:0050851), negative regulation of T cell activation (GO:0050868), immune system process (GO:0002376), regulation of lymphocyte activation (GO:0051249)

GO Molecular Function (3): protein kinase binding (GO:0019901), SH2 domain binding (GO:0042169), protein binding (GO:0005515)

GO Cellular Component (4): Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
lymphocyte activation	2
cytoplasm	2
cellular anatomical structure	2
immune response	1
immune system process	1
response to stimulus	1
intracellular anatomical structure	1
signal transduction	1
MAPK cascade	1
regulation of MAPK cascade	1
negative regulation of intracellular signal transduction	1
leukocyte activation	1
immune response-activating cell surface receptor signaling pathway	1
T cell activation	1
regulation of T cell activation	1
negative regulation of lymphocyte activation	1
negative regulation of leukocyte cell-cell adhesion	1
biological_process	1
regulation of leukocyte activation	1
kinase binding	1
protein domain specific binding	1
binding	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

650 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LAX1	TRAT1	Q6PIZ9	932
LAX1	RAB8A	P24407	926
LAX1	GRB2	P29354	793
LAX1	CD6	P30203	592
LAX1	LAT2	Q9GZY6	586
LAX1	CD5	P06127	512
LAX1	BTLA	Q7Z6A9	499
LAX1	PLCG1	P19174	481
LAX1	TNFRSF10B	O14763	477
LAX1	GRB7	Q14451	456
LAX1	LAT	O43561	444
LAX1	LIME1	Q9H400	432
LAX1	NUGGC	Q68CJ6	416
LAX1	RPS3	P23396	414
LAX1	FREM3	P0C091	412

IntAct

15 interactions, top by confidence:

A	B	Type	Score
GRB7	LAX1	psi-mi:“MI:0915”(physical association)	0.670
LAX1	GRB7	psi-mi:“MI:0915”(physical association)	0.670
LAX1	STAMBPL1	psi-mi:“MI:0915”(physical association)	0.560
RAB8A	LAX1	psi-mi:“MI:0403”(colocalization)	0.460
LAX1	RAB8A	psi-mi:“MI:0915”(physical association)	0.460
LAX1	MGME1	psi-mi:“MI:0915”(physical association)	0.400
IDH1	LAX1	psi-mi:“MI:0915”(physical association)	0.370
CTLA4	TRIM25	psi-mi:“MI:0403”(colocalization)	0.270
LAX1	CTLA4	psi-mi:“MI:0403”(colocalization)	0.270
LAX1	TRIM25	psi-mi:“MI:0403”(colocalization)	0.270

BioGRID (10): LAX1 (Two-hybrid), STAMBPL1 (Two-hybrid), CREB1 (Affinity Capture-MS), LAX1 (Two-hybrid), LAX1 (Two-hybrid), GRB7 (Two-hybrid), LAX1 (Affinity Capture-Western), LAX1 (Affinity Capture-Western), MGME1 (Affinity Capture-MS), LAX1 (Two-hybrid)

ESM2 similar proteins: A2A7Y5, A2VE02, A5D7K1, A6NKC9, O43561, O54957, O70601, O88834, P14784, P15391, P16382, P24394, P25917, P25918, Q13651, Q13796, Q2NL68, Q38J84, Q38J85, Q3KP66, Q3LRP3, Q3SYS8, Q3U1F9, Q3UU41, Q58CT8, Q5BK39, Q5FVQ5, Q5JTC6, Q5SX79, Q64322, Q6RFH4, Q6WG24, Q7M4L6, Q7TN12, Q7Z591, Q863Z5, Q86WR7, Q8BHB3, Q8BI17, Q8C708

Diamond homologs: Q58CT8, Q5FVQ5, Q8BHB3, Q8IWV1

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
LCK	“up-regulates activity”	LAX1	phosphorylation
SYK	“up-regulates activity”	LAX1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

69 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	51
Likely benign	8
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

392 predictions. Top by Δscore:

Variant	Effect	Δscore
1:203770933:GAAGC:G	donor_gain	1.0000
1:203770936:GC:G	donor_gain	1.0000
1:203771475:TGGGT:T	donor_loss	1.0000
1:203771476:GGGT:G	donor_loss	1.0000
1:203771477:GGT:G	donor_loss	1.0000
1:203771478:GTAG:G	donor_loss	1.0000
1:203772145:GTG:G	donor_gain	1.0000
1:203773873:A:AG	acceptor_gain	1.0000
1:203773874:G:GG	acceptor_gain	1.0000
1:203770826:A:AG	acceptor_gain	0.9900
1:203770827:G:GG	acceptor_gain	0.9900
1:203770827:GAA:G	acceptor_gain	0.9900
1:203770930:G:GT	donor_gain	0.9900
1:203770938:G:GG	donor_gain	0.9900
1:203771363:GCAGG:G	acceptor_loss	0.9900
1:203771364:CAG:C	acceptor_loss	0.9900
1:203771365:A:G	acceptor_loss	0.9900
1:203771366:G:A	acceptor_loss	0.9900
1:203771468:G:GT	donor_gain	0.9900
1:203771476:GG:G	donor_gain	0.9900
1:203771477:GG:G	donor_gain	0.9900
1:203771478:G:GG	donor_gain	0.9900
1:203771479:T:A	donor_loss	0.9900
1:203772062:TTTCA:T	acceptor_loss	0.9900
1:203772063:TTCAG:T	acceptor_loss	0.9900
1:203772064:TCAGG:T	acceptor_loss	0.9900
1:203772065:CA:C	acceptor_loss	0.9900
1:203772066:A:AG	acceptor_gain	0.9900
1:203772066:A:AT	acceptor_loss	0.9900
1:203772066:AG:A	acceptor_gain	0.9900

AlphaMissense

2638 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:203771440:T:A	N91K	0.928
1:203771440:T:G	N91K	0.928
1:203771436:A:T	K90I	0.916
1:203772100:A:C	S115R	0.912
1:203772102:T:A	S115R	0.912
1:203772102:T:G	S115R	0.912
1:203774069:T:A	N195K	0.892
1:203774069:T:G	N195K	0.892
1:203771439:A:T	N91I	0.887
1:203771437:A:C	K90N	0.882
1:203771437:A:T	K90N	0.882
1:203770868:G:A	G44R	0.872
1:203770868:G:C	G44R	0.872
1:203774294:C:A	N270K	0.867
1:203774294:C:G	N270K	0.867
1:203774034:A:C	S184R	0.863
1:203774036:C:A	S184R	0.863
1:203774036:C:G	S184R	0.863
1:203770869:G:A	G44E	0.859
1:203774372:T:A	N296K	0.831
1:203774372:T:G	N296K	0.831
1:203770878:C:A	A47D	0.826
1:203771442:T:G	I92S	0.825
1:203770904:T:C	C56R	0.823
1:203772097:T:C	F114L	0.823
1:203772099:C:A	F114L	0.823
1:203772099:C:G	F114L	0.823
1:203770887:T:G	L50R	0.817
1:203771442:T:C	I92T	0.812
1:203771444:T:G	Y93D	0.810

dbSNP variants (sampled 300 via entrez): RS1000194936 (1:203769300 G>A), RS1000213141 (1:203763271 C>T), RS1000288301 (1:203763440 C>T), RS1000338940 (1:203763776 C>G), RS1000452528 (1:203769477 T>A), RS1000540858 (1:203764835 G>A,C), RS1000744658 (1:203775030 T>A), RS1000969387 (1:203769364 C>A), RS1002147601 (1:203775923 G>T), RS1002299243 (1:203764053 G>T), RS1002434989 (1:203775643 T>A), RS1003030912 (1:203776779 T>A), RS1003197350 (1:203765966 G>A), RS1003542139 (1:203766855 T>TTTTCTA), RS1003658053 (1:203767035 T>A)

Disease associations

OMIM: gene MIM:619622 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST006661_122	Male-pattern baldness	1.000000e-15
GCST006661_4	Male-pattern baldness	8.000000e-14
GCST010725_76	Malaria	9.000000e-08
GCST010725_83	Malaria	1.000000e-11

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression	2
Nickel	increases expression	2
triphenyl phosphate	affects expression	1
sodium arsenite	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Dieldrin	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Aflatoxin B1	increases methylation	1
Asbestos, Crocidolite	affects expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.