BTLA

Summary

BTLA (B and T lymphocyte associated, HGNC:21087) is a protein-coding gene on chromosome 3q13.2, encoding B- and T-lymphocyte attenuator (Q7Z6A9). Inhibitory receptor on lymphocytes that negatively regulates antigen receptor signaling via PTPN6/SHP-1 and PTPN11/SHP-2.

This gene encodes a member of the immunoglobulin superfamily. The encoded protein contains a single immunoglobulin (Ig) domain and is a receptor that relays inhibitory signals to suppress the immune response. Alternative splicing results in multiple transcript variants. Polymorphisms in this gene have been associated with an increased risk of rheumatoid arthritis.

Source: NCBI Gene 151888 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 23 total
• MANE Select transcript: NM_181780

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21087
Approved symbol	BTLA
Name	B and T lymphocyte associated
Location	3q13.2
Locus type	gene with protein product
Status	Approved
Aliases	BTLA1, CD272
Ensembl gene	ENSG00000186265
Ensembl biotype	protein_coding
OMIM	607925
Entrez	151888

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000334529, ENST00000383680, ENST00000474965, ENST00000496584, ENST00000858278

RefSeq mRNA: 2 — MANE Select: NM_181780 NM_001085357, NM_181780

CCDS: CCDS33819, CCDS43130

Canonical transcript exons

ENST00000334529 — 5 exons

Exon	Start	End
ENSE00001336459	112471212	112471355
ENSE00001336463	112479455	112479769
ENSE00001336466	112463966	112466383
ENSE00001336472	112499271	112499472
ENSE00003460855	112469758	112469804

Expression profiles

Bgee: expression breadth ubiquitous, 152 present calls, max score 85.97.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.6389 / max 359.7013, expressed in 143 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
43751	0.9702	110
43752	0.7044	94
43754	0.4949	73
43749	0.2069	51
43750	0.1709	51
43753	0.0916	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lymph node	UBERON:0000029	85.97	gold quality
vermiform appendix	UBERON:0001154	83.43	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.06	gold quality
granulocyte	CL:0000094	82.70	gold quality
spleen	UBERON:0002106	79.48	gold quality
bone marrow cell	CL:0002092	78.75	gold quality
blood	UBERON:0000178	75.81	gold quality
caecum	UBERON:0001153	74.21	gold quality
mucosa of transverse colon	UBERON:0004991	73.96	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	72.79	gold quality
colonic epithelium	UBERON:0000397	72.26	gold quality
tonsil	UBERON:0002372	69.24	gold quality
bone marrow	UBERON:0002371	68.28	gold quality
leukocyte	CL:0000738	67.88	gold quality
rectum	UBERON:0001052	67.59	gold quality
monocyte	CL:0000576	66.15	gold quality
epithelium of nasopharynx	UBERON:0001951	65.68	gold quality
small intestine Peyer’s patch	UBERON:0003454	65.04	gold quality
gall bladder	UBERON:0002110	65.00	gold quality
superficial temporal artery	UBERON:0001614	63.07	gold quality
right uterine tube	UBERON:0001302	62.78	gold quality
small intestine	UBERON:0002108	62.46	gold quality
smooth muscle tissue	UBERON:0001135	58.06	gold quality
right coronary artery	UBERON:0001625	57.49	gold quality
descending thoracic aorta	UBERON:0002345	57.37	gold quality
oviduct epithelium	UBERON:0004804	57.28	silver quality
thoracic aorta	UBERON:0001515	57.13	gold quality
ascending aorta	UBERON:0001496	56.97	gold quality
aorta	UBERON:0000947	56.72	gold quality
popliteal artery	UBERON:0002250	56.57	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-8410	yes	12.95
E-ANND-3	yes	10.66
E-MTAB-7381	no	97.59

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

141 targeting BTLA, 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-8485	100.00	77.57	4731
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-548A-5P	99.94	71.27	3482

Literature-anchored findings (GeneRIF, showing 40)

• HVEM binds to B T lymphocyte attenuator (BTLA), an Ig family member, which inhibits T cell proliferation. (PMID:15568026)
• Binding of HVEM to BTLA attenuates T cell activation, identifying HVEM/BTLA as a coinhibitory receptor pair. (PMID:15647361)
• distinct herpesviruses target the HVEM-BTLA cosignaling pathway, suggesting the importance of this pathway in regulating T cell activation during host defenses. (PMID:16131544)
• 2.8-A crystal structure of the BTLA-HVEM complex shows that BTLA binds the N-terminal cysteine-rich domain of HVEM and employs a unique binding surface (PMID:16169851)
• BTLA is constitutively expressed on most CD4+ and CD8+ T cells and its expression progressively decreases upon T cell activation. (PMID:16643847)
• Cross-linking of BTLA with mAb 7D7 suppressed T lymphocyte proliferation, downregulated the expression of T cell activation marker CD25, and inhibited the production of interferon (IFN)-gamma, interleukin (IL)-2, IL-4, and IL-10. (PMID:17257317)
• BTLA is an inhibitory coreceptor of the B cell receptor (BCR) signaling pathway that attenuates B cell activation by targeting the downstream signaling molecules Syk and B cell linker protein (BLNK). (PMID:19155498)
• this study did not find any genetic contribution of the BTLA gene to the development of T1D and SLE in Japanese population. (PMID:19207938)
• BTLA gene polymorphisms may affect the sporadic breast cancer risk and prognosis in Chinese women in northeast of Heilongjiang Province (PMID:19585237)
• results suggest that down-regulation of the BTLA-HVEM pathway may be involved in germinal center B-cell activation. (PMID:19762537)
• the HVEM-BTLA cis-complex competitively inhibits HVEM activation by ligands expressed in the surrounding microenvironment, thus helping maintain T cells in the naive state. (PMID:19915044)
• In vitro blockade of the BTLA pathway augments allogeneic as well as cytomegalovirus-specific CD8-positive T cell proliferation, thereby enhancing the functional capacity of cytotoxic T lymphocytes in viral infections. (PMID:20693422)
• 590C single-nucleotide polymorphism of B- and T-lymphocyte attenuator was significantly associated with susceptibility to rheumatoid arthritis, but not to systemic lupus erythematosus or Sjogren’s syndrome. (PMID:21403914)
• BTLA expression on overall CD4(+) and CD8(+) T cells was progressively decreased in HIV-1 infection, which was directly correlated with disease progression and CD4(+) T-cell differentiation and activation (PMID:21592997)
• HVEM-BTLA cis complex provides intrinsic regulation in T cells serving as an interference mechanism silencing signals coming from the microenvironment. (PMID:21920726)
• The results of a mutagenesis study of HVEM suggest that the CD160 binding region on HVEM was slightly different from, but overlapped with, the BTLA binding site. (PMID:21959263)
• study described the expression and spatial distribution of HVEM and BTLA in rheumatoid arthritis synovial tissues, and results indicated that HVEM/BTLA may be involved in regulating the progress of joint inflammation (PMID:22179929)
• Added with PD-1 and Tim-3 blockades, BTLA blockade enhanced the expansion, proliferation, and cytokine production of NY-ESO-1-specific CD8(+) T cells. (PMID:22205715)
• These findings support role for BTLA and/or HVEM as potential, novel diagnostic markers of innate immune response/status and as therapeutic targets of sepsis. (PMID:22459947)
• BTLA-HVEM interactions impair minor histocompatibiility antigen-specific T cell functionality, providing a rationale for BTLA signaling blockade in post-stem cell transplantation. (PMID:22634623)
• The expression of BTLA has been observed on the surface of several kinds of cells within synovial tissues of RA patients, which indicates this signal might be involved in the regulation of local T cell activation and the pathogenesis of RA. (PMID:22691359)
• BTLA regulates human B cell responses and has implications for future development of therapies modulating B cells. (PMID:22903545)
• BTLA and HVEM may have roles in graft rejection after kidney transplantation (PMID:23375291)
• BTLA is a coreceptor that negatively regulates human Vgamma9Vdelta2 T-cell proliferation and has a role in immune escape for lymphoma cells (PMID:23692853)
• Data indicate taht lung function and the expressions of B, T lymphocyte attenuator (BTLA) and Treg cells were lower in patients with rheumatism than those in normal controls. (PMID:24909289)
• Focal deletions of the BTLA were associated with B-cell precursor acute lymphoblastic leukemia. (PMID:25261097)
• high BTLA expression levels in gastric cancer, identified by IHC, are an independent biomarker for the poor prognosis of patients with gastric cancer. (PMID:25334051)
• our study confirms that CD200/BTLA deletions are recurrent genetic lesions in the biology of BCP-ALL (PMID:26137961)
• BTLA expression declines on B cells of the aged and is associated with low responsiveness to the trivalent influenza vaccine. (PMID:26277622)
• Study showed a decreased expression of BTLA in ocular Behcet’s disease suggesting that it may be involved in the development and recurrence of this disease. (PMID:26841832)
• results indicate that polymorphisms rs1982809 situated in 3’ UTR nearby region of BTLA gene might be considered as low-penetrating risk factor for RCC, but results have to be confirmed in further studies (PMID:27234378)
• The impairment of Bregs and CD19+/BTLA+ cells could play an important pathogenic role in multiple sclerosis (MS). (PMID:27412504)
• this study shows that BTLA expression is likely associated with positive rather than conventional negative regulation of CD11c antigen-presenting cell stimulatory capacity (PMID:27717503)
• this study shows that in chronic hepatitis B virus patients, a subset of inefficient interferon-gamma producing antigen-specific CD8+ T cells recruited to the liver expressed high BTLA levels (PMID:27743606)
• rs1982809 BTLA gene polymorphism is associated with mRNA expression level and variations in the BTLA gene might be considered as potentially low-penetrating chronic lymphocytic leukemia risk factor (PMID:27933341)
• Plasma concentrations of soluble BTLA were increased early in sepsis/septic shock and correlated to severity of disease. A baseline concentration >21ng/mL was associated with a poor prognosis. (PMID:28056053)
• The percentage of circulating BTLA+CD4+ lymphocytes was significantly higher in patients with severe community acquired pneumonia. (PMID:28164546)
• Our data portrays BTLA as a molecule with the singular ability to provide both costimulatory and coinhibitory signals to activated CD8(+) T cells, resulting in extended survival, improved tumor control, and the development of a functional recall response. (PMID:28754817)
• Data suggest that both HVEM and UL144 bind a common epitope of BTLA, whether engaged in trans or in cis; these studies were conducted in cell lines representing B-lymphocytes, T-lymphocytes, and natural killer cells. (HVEM = human herpes virus entry mediator; UL144 = membrane glycoprotein UL144 of Human herpesvirus 5; BTLA = human B- and T-lymphocyte attenuator) (PMID:29061848)
• data provide the first evidence that increased BTLA predicts poor prognosis in patients with diffuse large B-cell lymphoma (DLBCL), and blockade of BTLA with other checkpoints may potentially represent a new strategy for immunotherapy of DLBCL. (PMID:29353075)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Btla	ENSMUSG00000052013
rattus_norvegicus	Btla	ENSRNOG00000030246

Protein

Protein identifiers

B- and T-lymphocyte attenuator — Q7Z6A9 (reviewed: Q7Z6A9)

Alternative names: B- and T-lymphocyte-associated protein

All UniProt accessions (1): Q7Z6A9

UniProt curated annotations — full annotation on UniProt →

Function. Inhibitory receptor on lymphocytes that negatively regulates antigen receptor signaling via PTPN6/SHP-1 and PTPN11/SHP-2. May interact in cis (on the same cell) or in trans (on other cells) with TNFRSF14. In cis interactions, appears to play an immune regulatory role inhibiting in trans interactions in naive T cells to maintain a resting state. In trans interactions, can predominate during adaptive immune response to provide survival signals to effector T cells.

Subunit / interactions. Interacts with tyrosine phosphatases PTPN6/SHP-1 and PTPN11/SHP-2. Interacts with TNFRSF14/HVEM (via cysteine-rich domain 1).

Subcellular location. Cell membrane.

Post-translational modifications. Phosphorylated on Tyr residues by TNFRSF14 and by antigen receptors cross-linking, both inducing association with PTPN6 and PTPN11. N-glycosylated.

Isoforms (2)

UniProt ID	Names	Canonical?
Q7Z6A9-1	1	yes
Q7Z6A9-2	2

RefSeq proteins (2): NP_001078826, NP_861445* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR039257	BTLA	Family

UniProt features (37 total): strand 10, sequence conflict 7, disulfide bond 3, sequence variant 3, mutagenesis site 3, glycosylation site 3, topological domain 2, signal peptide 1, chain 1, splice variant 1, transmembrane region 1, helix 1, domain 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
8F60	X-RAY DIFFRACTION	1.64
8F6L	X-RAY DIFFRACTION	1.85
8F6O	X-RAY DIFFRACTION	2.31
6NYP	X-RAY DIFFRACTION	2.7
2AW2	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z6A9-F1	67.56	0.32

Antibody-complex structures (SAbDab): 3 — 8F60, 8F6L, 8F6O

Functional residue map

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

Disulfide bonds (3): 58–115, 72–79, 34–63

Glycosylation sites (3): 75, 94, 110

Mutagenesis-validated functional residues (3):

Position	Phenotype
226	no change of phosphorylation implicated in interaction with ptpn6 and ptpn11. severe reduction of phosphorylation; when
257	no change of phosphorylation implicated in interaction with ptpn6 and ptpn11. severe reduction of phosphorylation; when
282	no change of phosphorylation implicated in interaction with ptpn6 and ptpn11. severe reduction of phosphorylation; when

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-9927353	Co-inhibition by BTLA
R-HSA-1280218	Adaptive Immune System
R-HSA-168256	Immune System
R-HSA-388841	Regulation of T cell activation by CD28 family

MSigDB gene sets: 253 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_NEGATIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_TOLERANCE_INDUCTION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_B_CELL_ACTIVATION, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_PRODUCTION_OF_MOLECULAR_MEDIATOR_OF_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_MEDIATED_IMMUNITY, GOBP_NEGATIVE_REGULATION_OF_CYTOKINE_PRODUCTION_INVOLVED_IN_IMMUNE_RESPONSE, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_B_CELL_PROLIFERATION, GOBP_NEGATIVE_REGULATION_OF_CELL_CELL_ADHESION, GOBP_REGULATION_OF_TOLERANCE_INDUCTION

GO Biological Process (4): adaptive immune response (GO:0002250), immune response-regulating cell surface receptor signaling pathway (GO:0002768), negative regulation of T cell proliferation (GO:0042130), immune system process (GO:0002376)

GO Molecular Function (2): signaling receptor activity (GO:0038023), protein binding (GO:0005515)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Regulation of T cell activation by CD28 family	1
Immune System	1
Adaptive Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
immune response	1
immune response-regulating signaling pathway	1
cell surface receptor signaling pathway	1
T cell proliferation	1
regulation of T cell proliferation	1
negative regulation of lymphocyte proliferation	1
negative regulation of T cell activation	1
biological_process	1
molecular transducer activity	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1552 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BTLA	TNFRSF14	Q92956	999
BTLA	VTCN1	Q7Z7D3	988
BTLA	PTPN11	Q06124	986
BTLA	CD160	O95971	949
BTLA	CD274	Q9NZQ7	940
BTLA	PDCD1	Q15116	884
BTLA	LAG3	P18627	880
BTLA	CTLA4	P16410	880
BTLA	TNFSF14	O43557	867
BTLA	LGALS9	O00182	831
BTLA	ICOS	Q9Y6W8	810
BTLA	HAVCR2	Q8TDQ0	804
BTLA	LGALS9B	Q3B8N2	800
BTLA	LGALS9C	Q6DKI2	799
BTLA	VSIR	Q9H7M9	794

IntAct

13 interactions, top by confidence:

A	B	Type	Score
RFXANK	RFXAP	psi-mi:“MI:0914”(association)	0.780
TNFRSF14	BTLA	psi-mi:“MI:0915”(physical association)	0.610
BTLA	TNFRSF14	psi-mi:“MI:0407”(direct interaction)	0.610
PTPN11	BTLA	psi-mi:“MI:0915”(physical association)	0.520
BTLA	BTLA	psi-mi:“MI:0407”(direct interaction)	0.440
PTPN6	BTLA	psi-mi:“MI:0915”(physical association)	0.400
BTLA	MOCS3	psi-mi:“MI:0914”(association)	0.350
BTLA	TUBB8	psi-mi:“MI:0914”(association)	0.350

BioGRID (30): PTPN11 (Affinity Capture-Western), MTHFD2L (Affinity Capture-MS), UBR1 (Affinity Capture-MS), NKIRAS2 (Affinity Capture-MS), TUBB8 (Affinity Capture-MS), TUBB1 (Affinity Capture-MS), BTLA (Affinity Capture-MS), IL17RA (Affinity Capture-MS), ERVMER34-1 (Affinity Capture-MS), THBS1 (Affinity Capture-MS), LAMB3 (Affinity Capture-MS), DDX19B (Affinity Capture-MS), LAMB2 (Affinity Capture-MS), BMP1 (Affinity Capture-MS), DHFR (Affinity Capture-MS)

ESM2 similar proteins: A0A8M9PDM1, B8JI67, D3YX43, D5K8A9, E9Q8Q8, F1LW30, O70535, O95256, O95727, P20352, P27931, P42703, P43303, Q05928, Q0VCB1, Q14956, Q149L7, Q2YDG7, Q3SXY7, Q5BVD1, Q5U462, Q6AXW8, Q6AY06, Q6GMZ9, Q6P7C7, Q6P7N7, Q6PHB0, Q6PNM1, Q6UXZ4, Q7Z6A9, Q80VH0, Q8C4Q9, Q8C5C9, Q8IYV9, Q8K1S2, Q8K4B4, Q8NDB2, Q8NEA5, Q8QHJ9, Q90VY2

Diamond homologs: Q6PNM1, Q7TSA3, Q7Z6A9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	19
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

631 predictions. Top by Δscore:

Variant	Effect	Δscore
3:112467322:T:C	acceptor_gain	1.0000
3:112469752:GCTT:G	donor_loss	1.0000
3:112469753:CTTAC:C	donor_loss	1.0000
3:112469754:TTACC:T	donor_loss	1.0000
3:112469755:TACCA:T	donor_loss	1.0000
3:112469756:A:C	donor_loss	1.0000
3:112469805:C:CC	acceptor_gain	1.0000
3:112479586:T:TA	donor_gain	1.0000
3:112499265:CCTTA:C	donor_loss	1.0000
3:112499266:CTTAC:C	donor_loss	1.0000
3:112499269:ACCAT:A	donor_loss	1.0000
3:112466379:TCAAC:T	acceptor_gain	0.9900
3:112466380:CAAC:C	acceptor_gain	0.9900
3:112466380:CAACC:C	acceptor_gain	0.9900
3:112466383:CCT:C	acceptor_loss	0.9900
3:112466384:C:CC	acceptor_gain	0.9900
3:112466385:T:A	acceptor_loss	0.9900
3:112467322:T:TC	acceptor_gain	0.9900
3:112469751:AGCTT:A	donor_loss	0.9900
3:112469756:A:AC	donor_gain	0.9900
3:112469757:C:CC	donor_gain	0.9900
3:112469773:T:TA	donor_gain	0.9900
3:112469801:TTTC:T	acceptor_gain	0.9900
3:112469803:TC:T	acceptor_gain	0.9900
3:112469803:TCC:T	acceptor_loss	0.9900
3:112469804:CC:C	acceptor_gain	0.9900
3:112469805:CTGG:C	acceptor_loss	0.9900
3:112469806:T:A	acceptor_loss	0.9900
3:112478062:G:C	donor_gain	0.9900
3:112479450:CTCA:C	donor_loss	0.9900

AlphaMissense

1891 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:112479645:C:A	W71C	0.993
3:112479645:C:G	W71C	0.993
3:112479480:G:C	S126R	0.988
3:112479480:G:T	S126R	0.988
3:112479482:T:G	S126R	0.988
3:112479647:A:G	W71R	0.987
3:112479647:A:T	W71R	0.987
3:112479591:C:A	W89C	0.984
3:112479591:C:G	W89C	0.984
3:112479517:C:G	R114P	0.983
3:112479685:C:G	C58S	0.982
3:112479686:A:T	C58S	0.982
3:112479514:C:G	C115S	0.981
3:112479515:A:T	C115S	0.981
3:112479686:A:G	C58R	0.981
3:112479521:A:C	Y113D	0.979
3:112479559:A:G	L100P	0.972
3:112479515:A:G	C115R	0.970
3:112479527:C:A	G111W	0.969
3:112466134:A:G	Y282H	0.966
3:112479526:C:T	G111E	0.958
3:112479643:C:G	C72S	0.957
3:112479644:A:T	C72S	0.957
3:112479684:G:C	C58W	0.957
3:112479513:A:C	C115W	0.956
3:112479593:A:G	W89R	0.954
3:112479593:A:T	W89R	0.954
3:112466124:A:T	I285K	0.953
3:112466133:T:C	Y282C	0.952
3:112479552:A:C	F102L	0.946

dbSNP variants (sampled 300 via entrez): RS1000192452 (3:112472472 G>A), RS1000249016 (3:112480298 C>A), RS1000268975 (3:112467274 G>A), RS1000278714 (3:112479985 G>A,T), RS1000428401 (3:112501216 A>C,T), RS1000436127 (3:112486178 G>A,T), RS1000627787 (3:112472267 T>C), RS1000689245 (3:112465720 T>A,G), RS1000761021 (3:112465485 T>G), RS1000915789 (3:112486367 A>C,T), RS1000941005 (3:112491356 T>C), RS1001012781 (3:112491049 C>A,T), RS1001056880 (3:112480419 T>C), RS1001109081 (3:112480695 T>C,G), RS1001137570 (3:112492963 G>A,T)

Disease associations

OMIM: gene MIM:607925 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003075_39	Cognitive decline rate in late mild cognitive impairment	6.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007710	cognitive decline measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, decreases methylation, increases methylation	1
sodium arsenite	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
licochalcone B	increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Fulvestrant	decreases methylation, affects cotreatment	1
Atrazine	increases expression	1
Benzo(a)pyrene	increases methylation	1
Antirheumatic Agents	decreases expression	1

Cellosaurus cell lines

5 cell lines: 3 cancer cell line, 2 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D1LR	Abcam K-562 BTLA KO	Cancer cell line	Female
CVCL_D2IC	Abcam Raji BTLA KO	Cancer cell line	Male
CVCL_E6P3	Genomeditech CHO-K1 H_BTLA	Spontaneously immortalized cell line	Female
CVCL_KA49	CHO-K1/BTLA	Spontaneously immortalized cell line	Female
CVCL_UQ23	Abcam Jurkat BTLA KO	Cancer cell line	Male

Clinical trials (associated diseases)

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