LCP2

Summary

LCP2 (lymphocyte cytosolic protein 2, HGNC:6529) is a protein-coding gene on chromosome 5q35.1, encoding Lymphocyte cytosolic protein 2 (Q13094). Adapter protein primarily involved in signaling pathways within T-cells, as well as other immune cells such as platelets, mast cells, and natural killer (NK) cells.

This gene encodes an adapter protein that acts as a substrate of the T cell antigen receptor (TCR)-activated protein tyrosine kinase pathway. The encoded protein associates with growth factor receptor bound protein 2, and is thought to play a role TCR-mediated intracellular signal transduction. A similar protein in mouse plays a role in normal T-cell development and activation. Mice lacking this gene show subcutaneous and intraperitoneal fetal hemorrhaging, dysfunctional platelets and impaired viability.

Source: NCBI Gene 3937 — RefSeq curated summary.

At a glance

• Gene–disease (curated): immunodeficiency 81 (Definitive, ClinGen)
• GWAS associations: 6
• Clinical variants (ClinVar): 101 total — 1 pathogenic
• GTEx eGene: eQTL in 16 tissues, sQTL in 14 (q < 0.05)
• Phenotypes (HPO): 16
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.47 (moderately constrained)
• MANE Select transcript: NM_005565
• Interaction hub: 2,148 STRING partners (top 6% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6529
Approved symbol	LCP2
Name	lymphocyte cytosolic protein 2
Location	5q35.1
Locus type	gene with protein product
Status	Approved
Aliases	SLP-76
Ensembl gene	ENSG00000043462
Ensembl biotype	protein_coding
OMIM	601603
Entrez	3937

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 7 protein_coding, 6 retained_intron, 3 nonsense_mediated_decay

MANE Select: ENST00000046794

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 5, TSL 3: 1, TSL 5: 2

ENST00000046794, ENST00000519149, ENST00000519594, ENST00000520322, ENST00000520344, ENST00000521416, ENST00000522760, ENST00000522823, ENST00000523369, ENST00000968849, ENST00000968850, ENST00000993249, ENST00000993250, ENST00001120265, ENST00001128984, ENST00001132305

RefSeq mRNA: 1 — MANE Select: NM_005565 NM_005565

CCDS: CCDS47339

Canonical transcript exons

ENST00000046794 — 21 exons

Exon	Start	End
ENSE00000609392	170250730	170250885
ENSE00000769265	170252434	170252511
ENSE00000769273	170258037	170258166
ENSE00000769281	170266808	170266891
ENSE00000769283	170267009	170267075
ENSE00000769287	170268385	170268482
ENSE00000769288	170270719	170270917
ENSE00000812799	170253119	170253213
ENSE00000812800	170261107	170261137
ENSE00000812801	170262635	170262742
ENSE00001026289	170262967	170262992
ENSE00001026292	170262842	170262861
ENSE00002100375	170246233	170248819
ENSE00002138597	170297534	170297777
ENSE00002533832	170258866	170258878
ENSE00003568261	170293310	170293372
ENSE00003576005	170275320	170275351
ENSE00003583243	170274301	170274338
ENSE00003585965	170287970	170288016
ENSE00003620466	170275795	170275860
ENSE00003693412	170256526	170256575

Expression profiles

Bgee: expression breadth ubiquitous, 262 present calls, max score 98.87.

FANTOM5 (CAGE): breadth broad, TPM avg 47.4024 / max 3769.2009, expressed in 652 samples.

Highest expression (Bgee): monocyte, mononuclear cell, leukocyte, granulocyte, blood.

Genetic regulation across tissues (GTEx eQTL / sQTL)

LCP2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 16 tissues and its splicing (sQTL) in 14 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 30 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	sqtl	1.6e-49	-0.68	5:170258159:C:T
Lung	sqtl	1.0e-14	-0.47	5:170258159:C:T
Adipose Subcutaneous	eqtl	3.8e-12	+0.26	5:170220527:C:T
Adipose Visceral Omentum	sqtl	1.3e-10	-0.97	5:170269752:C:T
Artery Tibial	eqtl	1.7e-09	-0.17	5:170252033:A:G
Esophagus Gastroesophageal Junction	eqtl	9.6e-07	+0.34	5:170378407:T:C
Skin Sun Exposed Lower leg	eqtl	2.4e-06	+0.11	5:170259003:T:C
Breast Mammary Tissue	eqtl	5.8e-05	+0.13	5:170332203:C:T
Whole Blood	eqtl	2.5e-04	-0.10	5:170296225:C:T
Nerve Tibial	eqtl	4.8e-04	-0.16	5:170241680:G:C
Skin Not Sun Exposed Suprapubic	eqtl	1.4e-03	-0.10	5:170248161:G:C
Nerve Tibial	sqtl	3.0e-03	-0.28	5:170258562:G:A
Artery Aorta	sqtl	3.6e-03	+0.35	5:170252033:A:G
Artery Tibial	sqtl	4.3e-03	-0.27	5:170258159:C:T
Skin Not Sun Exposed Suprapubic	sqtl	4.7e-03	-0.60	5:169609567:G:A
Testis	eqtl	4.8e-03	-0.16	5:170241778:C:T
Colon Transverse	sqtl	5.1e-03	+0.34	5:170244418:A:G
Thyroid	sqtl	5.2e-03	-0.27	5:170258159:C:T
Brain Substantia nigra	eqtl	5.4e-03	+0.21	5:170328106:C:T
Brain Frontal Cortex BA9	eqtl	5.6e-03	-0.22	5:170241715:A:G

FANTOM5 promoters

showing 10 of 11 alternative TSS:

Promoter ID	TPM avg	Samples expressed
64785	29.7135	630
64784	11.6594	471
64786	3.4118	382
64787	1.4698	235
64760	0.3890	153
64758	0.2619	115
64762	0.2270	78
64788	0.0974	53
64759	0.0773	40
64763	0.0584	10

Top tissues by expression

showing 100 of 293 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	98.87	gold quality
mononuclear cell	CL:0000842	98.75	gold quality
leukocyte	CL:0000738	98.74	gold quality
granulocyte	CL:0000094	98.28	gold quality
blood	UBERON:0000178	98.20	gold quality
bone marrow cell	CL:0002092	97.37	gold quality
spleen	UBERON:0002106	97.16	gold quality
vermiform appendix	UBERON:0001154	96.21	gold quality
lymph node	UBERON:0000029	96.20	gold quality
bone marrow	UBERON:0002371	95.91	gold quality
upper lobe of left lung	UBERON:0008952	95.08	gold quality
gall bladder	UBERON:0002110	94.87	gold quality
upper lobe of lung	UBERON:0008948	94.36	gold quality
thymus	UBERON:0002370	94.05	gold quality
right lung	UBERON:0002167	93.98	gold quality
colonic epithelium	UBERON:0000397	92.64	gold quality
omental fat pad	UBERON:0010414	92.56	gold quality
peritoneum	UBERON:0002358	92.48	gold quality
trabecular bone tissue	UBERON:0002483	91.47	gold quality
adipose tissue of abdominal region	UBERON:0007808	91.39	gold quality
rectum	UBERON:0001052	91.28	gold quality
caecum	UBERON:0001153	91.23	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.83	gold quality
lung	UBERON:0002048	89.95	gold quality
small intestine	UBERON:0002108	89.24	gold quality
right coronary artery	UBERON:0001625	88.76	gold quality
lower lobe of lung	UBERON:0008949	88.53	gold quality
superficial temporal artery	UBERON:0001614	88.49	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.77	gold quality
subcutaneous adipose tissue	UBERON:0002190	87.69	gold quality
tonsil	UBERON:0002372	87.33	gold quality
smooth muscle tissue	UBERON:0001135	86.41	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	86.10	gold quality
left uterine tube	UBERON:0001303	85.54	gold quality
tibial nerve	UBERON:0001323	85.33	gold quality
adipose tissue	UBERON:0001013	85.23	gold quality
amniotic fluid	UBERON:0000173	85.16	gold quality
right adrenal gland cortex	UBERON:0035827	85.14	gold quality
periodontal ligament	UBERON:0008266	84.78	gold quality
connective tissue	UBERON:0002384	84.49	gold quality
descending thoracic aorta	UBERON:0002345	84.35	gold quality
transverse colon	UBERON:0001157	84.29	gold quality
thoracic aorta	UBERON:0001515	84.08	gold quality
left adrenal gland	UBERON:0001234	84.02	gold quality
ascending aorta	UBERON:0001496	83.88	gold quality
left coronary artery	UBERON:0001626	83.74	gold quality
endocervix	UBERON:0000458	83.73	gold quality
spinal cord	UBERON:0002240	83.68	gold quality
left adrenal gland cortex	UBERON:0035825	83.68	gold quality
palpebral conjunctiva	UBERON:0001812	83.67	gold quality
epithelium of nasopharynx	UBERON:0001951	83.66	gold quality
nasopharynx	UBERON:0001728	83.65	gold quality
intestine	UBERON:0000160	83.57	gold quality
mucosa of stomach	UBERON:0001199	83.52	gold quality
right adrenal gland	UBERON:0001233	83.52	gold quality
body of stomach	UBERON:0001161	83.23	gold quality
right lobe of liver	UBERON:0001114	83.22	gold quality
sural nerve	UBERON:0015488	83.20	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.08	gold quality
visceral pleura	UBERON:0002401	82.99	gold quality
coronary artery	UBERON:0001621	82.97	gold quality
adrenal gland	UBERON:0002369	82.73	gold quality
adrenal cortex	UBERON:0001235	82.64	gold quality
urinary bladder	UBERON:0001255	82.61	gold quality
ectocervix	UBERON:0012249	82.53	gold quality
jejunal mucosa	UBERON:0000399	82.44	gold quality
minor salivary gland	UBERON:0001830	82.22	gold quality
stomach	UBERON:0000945	82.17	gold quality
colon	UBERON:0001155	81.97	gold quality
large intestine	UBERON:0000059	81.92	gold quality
aorta	UBERON:0000947	81.68	gold quality
mucosa of transverse colon	UBERON:0004991	81.60	gold quality
apex of heart	UBERON:0002098	81.47	gold quality
pleura	UBERON:0000977	81.34	gold quality
liver	UBERON:0002107	80.86	gold quality
duodenum	UBERON:0002114	80.85	gold quality
right atrium auricular region	UBERON:0006631	80.80	gold quality
diaphragm	UBERON:0001103	80.67	gold quality
muscle layer of sigmoid colon	UBERON:0035805	80.55	gold quality
left lobe of thyroid gland	UBERON:0001120	80.51	gold quality
fundus of stomach	UBERON:0001160	80.33	gold quality
lower esophagus	UBERON:0013473	80.21	gold quality
lower esophagus muscularis layer	UBERON:0035833	80.21	gold quality
parietal pleura	UBERON:0002400	80.18	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	80.15	gold quality
right lobe of thyroid gland	UBERON:0001119	80.09	gold quality
thyroid gland	UBERON:0002046	80.05	gold quality
tibial artery	UBERON:0007610	80.05	gold quality
popliteal artery	UBERON:0002250	80.01	gold quality
cingulate cortex	UBERON:0003027	79.92	gold quality
metanephros cortex	UBERON:0010533	79.87	gold quality
anterior cingulate cortex	UBERON:0009835	79.68	gold quality
right uterine tube	UBERON:0001302	79.62	gold quality
decidua	UBERON:0002450	79.59	gold quality
right frontal lobe	UBERON:0002810	79.55	gold quality
body of uterus	UBERON:0009853	79.45	gold quality
saliva-secreting gland	UBERON:0001044	79.41	gold quality
skin of leg	UBERON:0001511	79.33	gold quality
mouth mucosa	UBERON:0003729	79.29	gold quality
anatomical system	UBERON:0000467	79.27	gold quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-GEOD-84465	yes	38.32
E-CURD-122	yes	35.96
E-CURD-112	yes	35.41
E-ANND-3	yes	28.50
E-MTAB-10287	yes	28.25
E-HCAD-6	yes	18.29
E-MTAB-9543	yes	15.03
E-MTAB-9388	yes	12.92
E-MTAB-9067	yes	11.45
E-MTAB-8498	yes	11.11
E-CURD-119	yes	6.06
E-MTAB-6379	no	513.53
E-MTAB-5061	no	3.87

HPA expression

RNA tissue specificity: Group enriched

showing 60 of 77 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Bone marrow	tissue	154.8	high
Thymus	tissue	107.3
Spleen	tissue	76.4	high
Lymph node	tissue	72.5	high
Appendix	tissue	71.4	medium
Tonsil	tissue	44.4	high
Lung	tissue	29.7	medium
Gallbladder	tissue	26.8	medium
Urinary bladder	tissue	26.4	not detected
Liver	tissue	24.6	not detected
Small intestine	tissue	23.0	low
Adipose tissue	tissue	21.5	not detected
Placenta	tissue	20.6	medium
Hypothalamus	tissue	17.9
Stomach 1	tissue	16.6	low
Periaqueductal gray	tissue	16.6
Smooth muscle	tissue	15.5	not detected
Rectum	tissue	15.4	low
Substantia nigra	tissue	15.4
Corpus callosum	tissue	15.4
Septum	tissue	15.0
Duodenum	tissue	14.9	low
Spinal cord	tissue	14.9
Medulla oblongata	tissue	13.9
Colon	tissue	13.7	low
Adrenal gland	tissue	13.3	medium
Postcentral gyrus	tissue	12.4
Pons	tissue	12.1
Putamen	tissue	11.8
Amygdala	tissue	11.7
Midbrain	tissue	11.7
Ventral forebrain	tissue	11.3
Thalamus	tissue	11.1
Locus coeruleus	tissue	10.7
Basal ganglia	tissue	9.8	low
Cervix	tissue	9.7	not detected
Hippocampal formation	tissue	9.7
Choroid plexus	tissue	9.4
Esophagus	tissue	9.1	not detected
Superior colliculi	tissue	8.9
Cerebral cortex	tissue	8.6	low
Insular cortex	tissue	8.6
Breast	tissue	7.9	not detected
Entorhinal cortex	tissue	7.8
Olfactory bulb	tissue	7.8
Endometrium 1	tissue	7.7	low
Prefrontal cortex	tissue	7.6
Temporal cortex	tissue	7.6
Prostate	tissue	7.5	low
Retrosplenial cortex	tissue	7.5
Pancreas	tissue	7.3	low
Motor cortex	tissue	7.3
Hippocampus	tissue	6.9	low
Retrosplenial and cingulate cortex	tissue	6.9
Fallopian tube	tissue	6.4	low
Salivary gland	tissue	6.3	low
Seminal vesicle	tissue	6.1	low
Occipital cortex	tissue	6.0
Tongue	tissue	5.8
Somatosensory cortex	tissue	5.8

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Area parastriata, superior (44.7), Lateral funiculus (white matter) (22.8), Nucleus gracilis (21.7), Ventrolateral tegmental area, A5 NE cell group (20.4), Anterior thalamic nucleus, ventral (18.2).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): RUNX1, SPI1

miRNA regulators (miRDB)

Targeting LCP2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 54 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-3660	99.68	67.33	1149
HSA-MIR-4526	99.68	67.07	1136
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-548U	99.65	67.78	1463
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745

Functional genomics

gnomAD constraint: pLI 0.997, LOEUF 0.465, missense Z 0.99 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000046794 — one region, missense o/e 0.95.

Literature-anchored findings (GeneRIF, showing 40)

• Shb links SLP-76 and Vav with the CD3 complex in Jurkat T cells (SLP-76) (PMID:12084069)
• SLP-76 is essential for NF-kappa B activation and lipid raft translocation of protein kinase C theta and the I kappa B kinase complex. (PMID:12496421)
• SLP-76 is required for intracellular calcium ion mobilization in response to SDF-1alpha/CXCL12-induced prolonged activation of extracellular signal-related protein kinase in Jurkat T cells. (PMID:12817019)
• SLP-76 is necessary for T cell receptor stimulation-induced polarization of the T cell’s microtubule-organizing center, as it moves toward the interface of the T cell and antigen-presenting cell. (PMID:12847255)
• Study provides the first data to address the mechanisms controlling SLP-76 transcription by providing evidence for several key cis-regulatory elements in the promoter region. (PMID:14662865)
• the proline-rich domain in SLP-76 has a role in subcellular localization and T cell function (PMID:14722089)
• Data suggest that SLP-76 may play a role in signaling pathways by interacting with the p85 subunit of phosphoinositide 3-kinase (PI3K). (PMID:15388330)
• SLP-76 need not interact with SH3(PLC) to activate PLC-gamma1, and the P-I region of SLP-76 serves a structural role that is sequence-independent and is not directly related to protein-protein interactions (PMID:15623534)
• Data show that the adaptor molecules LAT and SLP-76 are specifically targeted by Yersinia to inhibit T cell activation. (PMID:15699071)
• TCR-induced association of Vav3 with SLP-76 is required for its membrane/IS localization and function (PMID:15708849)
• the Lck binding region of SLP-76 is essential for T cell antigen receptor signaling and normal T cell development and function (PMID:16354835)
• In T cells all SLP-76 proteins are in a approximately 400 kDa complex with the small adaptor protein Grb2-like adaptor protein Gads. (PMID:16356554)
• findings show that retinoic acid(RA) induced the expression of SLP-76, which when co-expressed with an RA-induced receptor, c-FMS, enhanced RA-induced cell differentiation and G0 cell cycle arrest (PMID:16439309)
• The costimulatory effect of CD6 is mediated through phosphorylation-dependent binding of a specific tyrosine residue, 662Y, in its cytoplasmic region to the adaptor SLP-76. (PMID:16914752)
• The P-I region deletion disrupted Vav association and reduced SLP-76-associated kinase activity. (PMID:17148460)
• The integrity of T-cell receptor signaling in vivo is sustained both by strong selection of SLP-76 for the Gads C-SH3 domain and by a capacity to buffer intrinsic crossreactivity. (PMID:17235283)
• phosphorylation of the adaptor molecule SLP-76 is essential for recruitment of the exchange factor Vav leading to Ca(2+) flux and IL-2 production (PMID:17237383)
• Required for activation of IL-2-inducible T cell kinase (ITK); furthermore, an ongoing physical interaction between SLP-76 and ITK is required to maintain ITK in an active conformation. (PMID:17420479)
• study reports that T cell costimulation by the integrin VLA-4 (alpha4beta1) required SLP-76 domains implicated in microcluster assembly (PMID:18549800)
• SLP-76 relocalizes to integrin-initiated signaling complexes by a mechanism different from that employed during TCR signaling and that SLP-76 relocalization corresponds to SLP-76-dependent integrin function in T cells. (PMID:19667077)
• SLP76 is differentially required for T cell receptor- compared to chemokine C-X-C receptor 4-mediated inside-out signaling pathways regulating T cell adhesion and migration in Jurkat T cells. (PMID:19812192)
• The results show that Bcr-Abl regulates the actin cytoskeleton and non-apoptotic membrane blebbing via a GADS/Slp-76/Nck1 adaptor protein pathway. (PMID:20079431)
• T-cell receptor (TCR)-induced association between ITK and SLP-76, recruitment and transphosphorylation of ITK, actin polarization at the T-cell contact site, and expression of Th2 cytokines (PMID:20457812)
• findings reconfigure the TCR signaling pathway by showing SLP-76 back-regulation of ZAP-70, an event that could ensure that signaling components are in balance for optimal T cell activation (PMID:20534575)
• Results define the composition, stoichiometry and specificity of interactions in the SLP-76, Nck and VAV1 complex, which is crucial for regulation of the actin machinery after T-cell activation. (PMID:20562827)
• LAT recruits Src homology 2 domain-containing leukocyte 76 kDa protein (SLP-76) following T-cell receptor ligation and membrane translocation of Akt and phosphatidylinositol 3-kinase (PI3K)phosphorylation in Jurkat cells, activating Akt signaling. (PMID:21282515)
• findings demonstrate the critical role of SLP-76-mediated signaling in initiating T-cell-directed immune responses both in vitro and in vivo (PMID:21469089)
• These data suggest a sequential mechanism whereby ZAP-70-dependent priming of SLP-76 at three N-terminal sites triggers reciprocal regulatory interactions between Itk and SLP-76, which are ultimately required to couple active Itk to PLC-gamma1. (PMID:21725281)
• The spatial correlation between kinase ZAP70 and adaptor SLP76 microclusters (MC) at the cell periphery and the effects of F-actin on MC assembly, were analysed. (PMID:21887278)
• Combining regulated deletion of endogenous SLP-76 with transgenic expression of a SLP-76 SH2 domain mutant demonstrates that the SLP-76 SH2 domain is required for peripheral T cell activation and positive selection of thymocytes. (PMID:21949020)
• our studies demonstrate a novel role for the adaptor molecule SLP-76 in regulating HIV-1 infection in T cells (PMID:22323535)
• both T cell activation and the association between SLP-76 and Nck. After T cell receptor stimulation, SLP-76 was phosphorylated, which enabled the binding of Nck. (PMID:22534133)
• Complementary phosphorylation sites in the adaptor protein SLP-76 promote synergistic activation of natural killer cells. (PMID:22786724)
• Nef employs a dual mechanism to disturb early TCR signaling by limiting the communication between LAT and SLP-76 (PMID:22802418)
• These findings reveal a novel role for SLP-76 in CXCR4-mediated T lymphocyte trafficking. (PMID:22806433)
• a novel regulation mechanism of SLP-76 by ubiquitination and proteasomal degradation of activated SLP-76, which is mediated by Ser-376 phosphorylation, leading to down-regulation of TCR signaling. (PMID:22902619)
• Unique modes of regulation of positive and negative feedback pathways in T cells by SLP-76. (PMID:23071622)
• Data indicate that the intracellular signaling of ITK-SYK requires both SLP-76 and the adapter function of SYK/ZAP-70 kinases. (PMID:23293025)
• analysis of a costimulatory mechanism by which CXCL12 and antigen converge at SLP-76 microcluster formation to enhance T cell responses (PMID:23901140)
• Data indicate a role for the SAM domain in mediating SLP-76 self-association for T-cell function. (PMID:23935094)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	lcp2b	ENSDARG00000036215
danio_rerio	lcp2a	ENSDARG00000055955
danio_rerio		ENSDARG00000091321
mus_musculus	Lcp2	ENSMUSG00000002699
rattus_norvegicus	Lcp2	ENSRNOG00000005620

Paralogs (3): BLNK (ENSG00000095585), CLNK (ENSG00000109684), SH2D6 (ENSG00000152292)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1321402) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 38 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased thymocyte number	2
abnormal T cell subpopulation ratio	2
abnormal negative T cell selection	2
decreased T cell number	2
impaired natural killer cell mediated cytotoxicity	2
decreased CD4-positive, alpha-beta T cell number	2
small thymus	1
abnormal lens morphology	1
cataract	1
thymus hypoplasia	1
arrested T cell differentiation	1
abnormal T cell activation	1
autoimmune response	1
abnormal T cell differentiation	1
abnormal double-negative T cell morphology	1
abnormal double-positive T cell morphology	1
abnormal effector T cell morphology	1
abnormal T cell physiology	1
increased IgG level	1
increased IgE level	1
abnormal positive T cell selection	1
decreased double-negative T cell number	1
increased double-negative T cell number	1
decreased T cell proliferation	1
abnormal platelet activation	1

+13 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Gallus gallus	Q9YGC1	48.1%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
LINC01187	ncRNA	100507267
C5orf58	protein-coding	133874
LINC01366	ncRNA	257358
KCNIP1	protein-coding	30820
KCNMB1	protein-coding	3779
FOXI1	protein-coding	2299
KCNIP1-OT1	ncRNA	101928033
MIR378E	ncRNA	100616498
DOCK2	protein-coding	1794

Protein

Protein identifiers

Lymphocyte cytosolic protein 2 — Q13094 (reviewed: Q13094)

Alternative names: SH2 domain-containing leukocyte protein of 76 kDa, SLP-76 tyrosine phosphoprotein

All UniProt accessions (3): E5RKA2, E7ESF6, Q13094

UniProt curated annotations — full annotation on UniProt →

Function. Adapter protein primarily involved in signaling pathways within T-cells, as well as other immune cells such as platelets, mast cells, and natural killer (NK) cells. Plays a crucial role for transducing signal from the T-cell receptor (TCR) after antigen recognition leading to T-cell activation. Mechanistically, once phosphorylated by the kinase ZAP70, mediates interactions with the guanine-nucleotide exchange factor VAV1, the adapter protein NCK and the kinase ITK. In turn, stimulates the activation of PKC-theta/PRKCQ and NF-kappa-B transcriptional activity in response to CD3 and CD28 costimulation. Also plays an essential role in AGER-induced signaling pathways including p38 MAPK and ERK1/2 activation leading to cytokine release and pro-inflammatory responses.

Subunit / interactions. Interacts with SLA. Interacts with CBLB. Interacts with GRB2. Interacts with SHB. Interacts with PRAM1. Interacts (via SH2 domain) with CD6 (via tyrosine phosphorylated C-terminus). Interacts with FYB1 and the phosphorylated form of FYB2. Interacts with 14-3-3 adapter/YWHAZ; this phosphorylation leads to YWHAZ proteolytic degradation. Interacts with VAV1; this interaction plays a role in TCR-mediated cytokine production. Interacts with AGER; this interaction plays an important role in AGER-mediated pro-inflammatory responses and cytokine release.

Subcellular location. Cytoplasm.

Tissue specificity. Highly expressed in spleen, thymus and peripheral blood leukocytes. Highly expressed also in T-cell and monocytic cell lines, expressed at lower level in B-cell lines. Not detected in fibroblast or neuroblastoma cell lines.

Post-translational modifications. Phosphorylated after T-cell receptor activation by ZAP70, ITK and TXK, which leads to the up-regulation of Th1 preferred cytokine IL-2. SYK-dependent phosphorylation is required for recruitment of PI3K signaling components.

Disease relevance. Immunodeficiency 81 (IMD81) [MIM:619374] An autosomal recessive disorder characterized by recurrent infections, including fungal infections, associated with T cell, neutrophil, and NK cell dysfunction. B cells may also show maturation abnormalities. Other features include autoimmune hemolytic anemia and abnormal platelet aggregation. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The SH2 domain mediates interaction with phosphorylated CD6. The SH2 domain mediates interaction with SHB. Possesses an N-terminal acidic domain containing three tyrosine phosphorylation motifs, a central proline-rich region, and a C-terminal SH2 domain.

RefSeq proteins (1): NP_005556* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000980	SH2	Domain
IPR001660	SAM	Domain
IPR013761	SAM/pointed_sf	Homologous_superfamily
IPR036860	SH2_dom_sf	Homologous_superfamily
IPR051751	SLP76_BLNK	Family

Pfam: PF00017, PF07647

UniProt features (27 total): helix 10, compositionally biased region 5, modified residue 4, domain 2, turn 2, chain 1, sequence variant 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

5 structures by resolution:

PDB	Title	Method	Resolution (Å)
6ZCJ	14-3-3sigma in complex with SLP76pS376 phosphopeptide crystal structure	X-RAY DIFFRACTION	1.53
1YWO	Phospholipase Cgamma1 SH3 in complex with a SLP-76 motif	X-RAY DIFFRACTION	1.81
1H3H	Structural Basis for Specific Recognition of an RxxK-containing SLP-76 peptide by the …	SOLUTION NMR
2EAP	Solution structure of the N-terminal SAM-domain of human lymphocyte cytosolic protein 2	SOLUTION NMR
2ROR	Solution structure of the VAV1 SH2 domain complexed with a tyrosine-phosphorylated …	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13094-F1	63.50	0.21

Human Protein Atlas

Protein class: Predicted intracellular proteins, Disease related genes, Human disease related genes, Primary immunodeficiency

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol

Antibody reliability (HPA): IH enhanced · IF supported

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 (4)

Type	Positions
Phosphoserine	207, 376, 410
Phosphotyrosine	23

Function

Pathways and Gene Ontology

Reactome pathways

3 curated (TAS) of 13; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

13 pathways:

ID	Pathway	Evidence
R-HSA-2424491	DAP12 signaling	curated
R-HSA-2871796	FCERI mediated MAPK activation	curated
R-HSA-114604	GPVI-mediated activation cascade	curated
R-HSA-1280218	Adaptive Immune System	—
R-HSA-2172127	DAP12 interactions	—
R-HSA-2871809	FCERI mediated Ca+2 mobilization	electronic
R-HSA-2454202	Fc epsilon receptor (FCERI) signaling	—
R-HSA-202433	Generation of second messenger molecules	electronic
R-HSA-109582	Hemostasis	—
R-HSA-168256	Immune System	—
R-HSA-168249	Innate Immune System	—
R-HSA-76002	Platelet activation, signaling and aggregation	—
R-HSA-202403	TCR signaling	—

MSigDB gene sets: 435 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, GSE45365_NK_CELL_VS_CD8A_DC_UP, WALLACE_PROSTATE_CANCER_RACE_UP, REACTOME_INNATE_IMMUNE_SYSTEM, HNF3ALPHA_Q6, MCLACHLAN_DENTAL_CARIES_UP, GOBP_REGULATION_OF_PHOSPHORYLATION, GNF2_CASP8, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, ZHAN_MULTIPLE_MYELOMA_MF_UP, MODULE_45, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, MODULE_16

GO Biological Process (7): immune response (GO:0006955), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), intracellular signal transduction (GO:0035556), mast cell activation (GO:0045576), positive regulation of protein kinase activity (GO:0045860), T cell receptor signaling pathway (GO:0050852), immune system process (GO:0002376)

GO Molecular Function (2): protein-macromolecule adaptor activity (GO:0030674), protein binding (GO:0005515)

GO Cellular Component (5): cytoplasm (GO:0005737), cytosol (GO:0005829), cell-cell junction (GO:0005911), TCR signalosome (GO:0036398), plasma membrane raft (GO:0044853)

Reactome top-level categories

8 top-level categories:

Category	Pathways
Fc epsilon receptor (FCERI) signaling	2
Immune System	2
Innate Immune System	2
Platelet activation, signaling and aggregation	1
TCR signaling	1
DAP12 interactions	1
Adaptive Immune System	1
Hemostasis	1

GO top-level categories

23 GO namespaces:

Category	Terms
intracellular anatomical structure	2
cellular anatomical structure	2
immune system process	1
response to stimulus	1
enzyme-linked receptor protein signaling pathway	1
signal transduction	1
myeloid leukocyte activation	1
positive regulation of protein phosphorylation	1
protein kinase activity	1
positive regulation of kinase activity	1
regulation of protein kinase activity	1
antigen receptor-mediated signaling pathway	1
biological_process	1
protein binding	1
molecular adaptor activity	1
binding	1
cytoplasm	1
anchoring junction	1
protein-containing complex	1
T cell receptor complex	1
plasma membrane	1
membrane raft	1
plasma membrane region	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 5 of 14 annotations. The rest are phylogenetic / computational / electronic (IEA).

5 experimentally-supported GO terms:

GO term	NS	Evidence
T cell receptor signaling pathway	BP	direct assay
positive regulation of protein kinase activity	BP	expression pattern
TCR signalosome	CC	direct assay
cytosol	CC	direct assay
plasma membrane raft	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 2,148 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LCP2	ZAP70	P43403	951
LCP2	GRAP2	O75791	915
LCP2	SYK	P43405	900
LCP2	LCK	P06239	887
LCP2	LAT	O43561	878
LCP2	VAV1	P15498	877
LCP2	FYB1	O15117	869
LCP2	PLCG2	P16885	865
LCP2	GRB2	P29354	850
LCP2	UBASH3A	P57075	815
LCP2	UBASH3B	Q8TF42	804
LCP2	SRC	P12931	792
LCP2	FYN	P06241	784
LCP2	LYN	P07948	777
LCP2	CD247	P20963	773

IntAct

Human interaction partners of LCP2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 35 partners by confidence:

Partner	Interaction type	MIscore	Records
GRAP2	physical association	0.980	49
GRB2	physical association	0.920	17
FYB1	physical association	0.900	10
NCK1	physical association	0.880	20
NCK2	physical association	0.820	10
STAM2	physical association	0.790	9
FXR2	physical association	0.780	7
VAV1	association	0.760	8
ITK	physical association	0.730	3
GOLGA2	physical association	0.720	6
EGFR	physical association	0.630	3
PLCG1	proximity	0.590	7
MAP4K3	direct interaction	0.590	3
ELOVL6	physical association	0.560	3
LNX1	physical association	0.560	3
LCK	association	0.560	2
CD6	physical association	0.500	2
STAM	direct interaction	0.440	3
SRC	physical association	0.400	2
CBL	physical association	0.400	1
FYN	physical association	0.400	1
HCK	physical association	0.400	1
HMGN1	physical association	0.400	1
KRT8	physical association	0.400	1
PIK3R1	physical association	0.400	1
SHC1	physical association	0.400	1
ALK	physical association	0.370	1
EP300	physical association	0.370	1
SH3GL2	physical association	0.370	1
YBX1	physical association	0.370	1

BioGRID (120 interactions; top human partners by supporting records): GRAP2 (Two-hybrid; 25 records), GRB2 (Two-hybrid; 13 records), PLCG1 (Reconstituted Complex; 7 records), FYB (Two-hybrid; 5 records), CBL (Affinity Capture-Western; 4 records), PIK3R1 (Two-hybrid; 4 records), EGFR (Two-hybrid; 3 records), FXR2 (Two-hybrid; 3 records), ITK (Affinity Capture-Western; 3 records), NCK1 (Affinity Capture-Western; 3 records), NCK2 (Two-hybrid; 3 records), PTPN6 (Reconstituted Complex; 3 records), TNK2 (Affinity Capture-Western; 3 records), VAV1 (Affinity Capture-Western; 3 records), GOLGA2 (Two-hybrid; 2 records)

SIGNOR signaling

showing 8 of 20 signaling interactions:

A	Effect	B	Mechanism
ZAP70	“up-regulates activity”	LCP2	phosphorylation
MAP4K1	up-regulates	LCP2	phosphorylation
TXK	“up-regulates activity”	LCP2	phosphorylation
MAP4K1	“down-regulates activity”	LCP2	phosphorylation
ZAP70	up-regulates	LCP2	phosphorylation
TXK	up-regulates	LCP2	phosphorylation
FYN	down-regulates	LCP2	phosphorylation
LCK	unknown	LCP2	phosphorylation

Protein complexes (CORUM) (10)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

10 complexes by size:

Complex	Subunits	Members
LAT-VAV1 multiprotein complex	7	PIK3R1, PLCG1, VAV1, CBL, GRB2, LAT, LCP2
CBL-GRB2-LCP2-SHC1 complex	4	CBL, GRB2, LCP2, SHC1
★ GRB2-LCP2-LYN-PLCG2 complex	4	GRB2, LCP2, LYN, PLCG2
LAT-LCP2-PLCG1-SOS1 complex	4	LAT, LCP2, PLCG1, SOS1
★ LAT-LCK-LCP2-PLCG1 complex	4	LCP2, PLCG1, LAT, LCK
CBL-GRB2-LCP2 complex	3	CBL, GRB2, LCP2
★ ITK-LCP2-PLCG1 complex	3	ITK, LCP2, PLCG1
LCP2-PLCG1-VAV1 complex	3	VAV1, LCP2, PLCG1
PLC-gamma-2-SLP-76 complex	2	LCP2, PLCG2
★ ITK-LCP2 complex	2	ITK, LCP2

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 35 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Constitutive Signaling by EGFRvIII	6	138.2×	2e-10
InlB-mediated entry of Listeria monocytogenes into host cell	5	122.8×	9e-09
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	6	110.5×	6e-10
Signaling by ERBB2 ECD mutants	5	108.3×	2e-08
Regulation of KIT signaling	5	96.9×	3e-08
Regulation of signaling by CBL	6	96.1×	1e-09
DAP12 signaling	8	95.1×	4e-12
Signaling by ALK	5	92.1×	4e-08

GO biological processes:

GO term	Partners	Fold	FDR
T cell activation	6	44.4×	9e-07
epidermal growth factor receptor signaling pathway	6	42.5×	9e-07
T cell receptor signaling pathway	7	30.4×	9e-07
integrin-mediated signaling pathway	5	22.9×	1e-04
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	5	11.2×	2e-03
intracellular signal transduction	10	10.9×	2e-06
negative regulation of apoptotic process	7	7.0×	1e-03

Disease & clinical

Genetic variants

Variant evidence for LCP2: 101 ClinVar records (1 pathogenic / likely pathogenic); 6 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	62
Likely benign	15
Benign	15

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
1172796	NM_005565.5(LCP2):c.957+1G>A	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore LCP2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 34 predictions of 1,623):

Position(s)	Effect	Δscore	Sites
5:170250728–170250729	donor_loss	1.0000	3
5:170250773	donor_gain	1.0000
5:170250886–170250887	acceptor_loss	1.0000	5
5:170262655	donor_gain	1.0000
5:170275861–170275862	acceptor_loss	1.0000	6
5:170293373–170293374	acceptor_loss	1.0000	5
5:170250728	donor_loss	0.9900
5:170250886	acceptor_loss	0.9900
5:170253117–170253118	donor_loss	0.9900	5
5:170253214–170253215	acceptor_loss	0.9900	6

AlphaMissense

908 missense substitutions predicted likely pathogenic (of 3,510 scored), across 221 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M462	9	0.926	0.997
N471	8	0.991	1.000
F495	8	0.978	0.999
F57	8	0.968	0.999
D514	8	0.964	0.993
F46	8	0.961	0.999
D442	8	0.925	0.987
F24	8	0.903	0.995
D175	8	0.869	0.956
D53	8	0.861	0.968
D31	8	0.832	0.969
D112	8	0.786	0.946
F445	7	0.997	1.000
W15	7	0.983	0.998
W422	7	0.982	0.999
F505	7	0.981	0.998
E146	7	0.975	0.987
C524	7	0.968	0.997
D449	7	0.953	0.971
E433	7	0.947	0.978

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Disease associations

OMIM: gene MIM:601603 | disease phenotypes: MIM:619374

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
immunodeficiency 81	Strong	Autosomal recessive	3

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
immunodeficiency 81	Definitive	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (1 panels, 1 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

1 panels:

Panel	Rating
Primary immunodeficiency or monogenic inflammatory bowel disease	green

Mondo (1): immunodeficiency 81 (MONDO:0030302)

HPO phenotypes

16 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000967	Petechiae
HP:0000988	Skin rash
HP:0001890	Autoimmune hemolytic anemia
HP:0002719	Recurrent infections
HP:0002721	Immunodeficiency
HP:0003203	Decreased neutrophil oxidative burst
HP:0008320	Impaired collagen-induced platelet aggregation
HP:0012177	Abnormal natural killer cell physiology
HP:0025615	Abscess
HP:0030388	Decreased class-switched memory B cell proportion
HP:0031402	Decreased antigen-specific T cell proliferation
HP:0031545	Abnormally low T cell receptor excision circle level
HP:0032218	Decreased total CD4+ T cell proportion
HP:0040238	Impaired neutrophil chemotaxis
HP:0100838	Recurrent cutaneous abscess formation

GWAS associations

6 associations:

Study	Trait	p-value
GCST90002381_102	Eosinophil count	5e-14
GCST90002382_188	Eosinophil percentage of white cells	3e-13
GCST005859_3	Liver transplant-free survival in primary sclerosing cholangitis (time to event)	7e-8
GCST003830_11	Response to bronchodilator in chronic obstructive pulmonary disease (change in FEV1)	6e-7
GCST002481_3	Acne (severe)	3e-6
GCST012190_5	Body mass index and diastolic blood pressure (bivariate analysis)	5e-6

EFO canonical traits (from GWAS)

5 canonical traits:

EFO ID	Trait name
EFO:0005921	FEV change measurement
EFO:0004340	body mass index
EFO:0006336	diastolic blood pressure
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6196086 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

47 measured of 47 human assays (47 total across all organisms); most potent 47 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
5-Cyclopropyl-6-(3-methylimidazo[4,5-c]pyridin-7-yl)-3-(4-morpholinoanilino)pyrazine-2-carboxamide	IC50	9 nM
5-(Methylamino)-6-(3-methylimidazo[4,5-c]pyridin-7-yl)-3-(4-morpholinoanilino)pyrazine-2-carboxamide	IC50	13 nM
4-[(1R)-1-aminopropyl]-2-[6-[(5S)-5-methyl-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-3-yl]-2-pyridinyl]-6-[(2R)-2-methylpyrrolidin-1-yl]-3H-pyrrolo[3,4-c]pyridin-1-one	IC50	17 nM	US-11684616: Azalactam compounds as HPK1 inhibitors
5-Methoxy-6-(3-methylimidazo[4,5-c]pyridin-7-yl)-3-(4-morpholinoanilino)pyrazine-2-carboxamide	IC50	20 nM
[(3R,4S)-4-methyloxolan-3-yl] N-[8-amino-6-(8-ethyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-7-yl)-7-fluoroisoquinolin-3-yl]carbamate	IC50	24 nM	US-11612606: 8-aminoisoquinoline compounds and uses thereof
(3-cyanocyclobutyl) N-[8-amino-7-fluoro-6-(8-methyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-7-yl)isoquinolin-3-yl]carbamate	IC50	26 nM	US-11612606: 8-aminoisoquinoline compounds and uses thereof
[3-(2-hydroxypropan-2-yl)cyclobutyl] N-[8-amino-7-fluoro-6-(8-methyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-7-yl)isoquinolin-3-yl]carbamate	IC50	32 nM	US-11612606: 8-aminoisoquinoline compounds and uses thereof
5-(Difluoromethyl)-6-(3-methylimidazo[4,5-c]pyridin-7-yl)-3-(4-morpholinoanilino)pyrazine-2-carboxamide	IC50	32 nM
4-(methylaminomethyl)-6-[(2R)-2-methylpyrrolidin-1-yl]-2-[6-(4-propyl-1,2,4-triazol-3-yl)-2-pyridinyl]-3H-pyrrolo[3,4-c]pyridin-1-one	IC50	34 nM	US-11142525: Azalactam compounds as HPK1 inhibitors
[(4R)-4-methyloxolan-3-yl] N-[8-amino-7-fluoro-6-(8-methyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-7-yl)isoquinolin-3-yl]carbamate	IC50	36 nM	US-11612606: 8-aminoisoquinoline compounds and uses thereof
2-[6-[(5S)-5-ethyl-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-3-yl]-2-pyridinyl]-4-(methylaminomethyl)-6-[methyl(propan-2-yl)amino]-3H-pyrrolo[3,4-c]pyridin-1-one	IC50	37 nM	US-11684616: Azalactam compounds as HPK1 inhibitors
[(1S)-2-cyanocyclopentyl] N-[8-amino-7-fluoro-6-(8-methyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-7-yl)isoquinolin-3-yl]carbamate	IC50	38 nM	US-11612606: 8-aminoisoquinoline compounds and uses thereof
N-[8-amino-7-fluoro-6-(8-methyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-7-yl)isoquinolin-3-yl]-3-methylazetidine-1-carboxamide	IC50	41 nM	US-11612606: 8-aminoisoquinoline compounds and uses thereof
N-[8-amino-7-fluoro-6-(8-methyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-7-yl)isoquinolin-3-yl]-3-fluoro-3-methylazetidine-1-carboxamide	IC50	46 nM	US-11612606: 8-aminoisoquinoline compounds and uses thereof
4-(methylaminomethyl)-2-[6-[(5S)-5-methyl-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-3-yl]-2-pyridinyl]-6-[methyl(propan-2-yl)amino]-3H-pyrrolo[3,4-c]pyridin-1-one	IC50	47 nM	US-11684616: Azalactam compounds as HPK1 inhibitors
3-(2-Fluoro-4-morpholino-anilino)-5-(methylamino)-6-(3-methylimidazo[4,5-c]pyridin-7-yl)pyrazine-2-carboxamide	IC50	47 nM
[(3R)-oxolan-3-yl] N-[8-amino-7-fluoro-6-(8-methyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-7-yl)isoquinolin-3-yl]carbamate	IC50	48 nM	US-11612606: 8-aminoisoquinoline compounds and uses thereof
5-Cyclopropyl-3-[(1,3-dimethylpyrazol-4-yl)amino]-6-(3-methylimidazo[4,5-c]pyridin-7-yl)pyrazine-2-carboxamide	IC50	48 nM
2-[6-[(5R)-5-(fluoromethyl)-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-3-yl]-2-pyridinyl]-4-(methylaminomethyl)-6-[methyl(propan-2-yl)amino]-3H-pyrrolo[3,4-c]pyridin-1-one	IC50	52 nM	US-11684616: Azalactam compounds as HPK1 inhibitors
4-[(1R)-1-aminoethyl]-2-[6-[(5S)-5-methyl-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-3-yl]-2-pyridinyl]-6-[(2R)-2-methylpyrrolidin-1-yl]-3H-pyrrolo[3,4-c]pyridin-1-one	IC50	53 nM	US-11684616: Azalactam compounds as HPK1 inhibitors
4-[(1R)-1-aminopropyl]-2-[6-(4-ethyl-1,2,4-triazol-3-yl)-2-pyridinyl]-6-[(2R)-2-methylpyrrolidin-1-yl]-3H-pyrrolo[3,4-c]pyridin-1-one	IC50	53 nM	US-11684616: Azalactam compounds as HPK1 inhibitors
[(2S,3R)-2-methyloxolan-3-yl] N-[8-amino-7-fluoro-6-(8-methyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-7-yl)isoquinolin-3-yl]carbamate	IC50	62 nM	US-11612606: 8-aminoisoquinoline compounds and uses thereof
[(3S,4R)-4-methoxyoxolan-3-yl] N-[8-amino-7-fluoro-6-(8-methyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-7-yl)isoquinolin-3-yl]carbamate	IC50	62 nM	US-11612606: 8-aminoisoquinoline compounds and uses thereof
(3-hydroxy-3-methylcyclobutyl) N-[8-amino-7-fluoro-6-[4-methyl-5-(methylamino)-3-pyridinyl]isoquinolin-3-yl]carbamate	IC50	64 nM	US-11612606: 8-aminoisoquinoline compounds and uses thereof
[(3R,4S)-4-fluorooxolan-3-yl] N-[8-amino-7-fluoro-6-(8-methyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-7-yl)isoquinolin-3-yl]carbamate	IC50	66 nM	US-11612606: 8-aminoisoquinoline compounds and uses thereof
5-Methyl-6-(3-methylimidazo[4,5-c]pyridin-7-yl)-3-(4-morpholinoanilino)pyrazine-2-carboxamide	IC50	66 nM
6-(dimethylamino)-4-(methylaminomethyl)-2-[6-[4-[(2S)-4,4,4-trifluorobutan-2-yl]-1,2,4-triazol-3-yl]-2-pyridinyl]-3H-pyrrolo[3,4-c]pyridin-1-one	IC50	70 nM	US-11142525: Azalactam compounds as HPK1 inhibitors
3-[(1,3-Dimethylpyrazol-4-yl)amino]-5-(methylamino)-6-(3-methylimidazo[4,5-c]pyridin-7-yl)pyrazine-2-carboxamide	IC50	77 nM
4-(methylaminomethyl)-6-[methyl(propan-2-yl)amino]-2-[6-(5-methyl-4-propyl-1,2,4-triazol-3-yl)-2-pyridinyl]-3H-pyrrolo[3,4-c]pyridin-1-one	IC50	81 nM	US-11142525: Azalactam compounds as HPK1 inhibitors
CHEMBL6147087	IC50	82 nM
4-(methylaminomethyl)-6-[methyl(propan-2-yl)amino]-2-[6-(4-propyl-1,2,4-triazol-3-yl)-2-pyridinyl]-3H-pyrrolo[3,4-c]pyridin-1-one	IC50	87 nM	US-11142525: Azalactam compounds as HPK1 inhibitors
oxan-4-yl N-[8-amino-7-fluoro-6-(8-methyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-7-yl)isoquinolin-3-yl]carbamate	IC50	97 nM	US-11612606: 8-aminoisoquinoline compounds and uses thereof
5-Cyclopropyl-3-[[1-(2,2-difluoroethyl)-3-methyl-pyrazol-4-yl]amino]-6-(3-methylimidazo[4,5-c]pyridin-7-yl)pyrazine-2-carboxamide	IC50	98 nM
6-(dimethylamino)-4-(methylaminomethyl)-2-[6-(4-propan-2-yl-1,2,4-triazol-3-yl)-2-pyridinyl]-3H-pyrrolo[3,4-c]pyridin-1-one	IC50	112 nM	US-11142525: Azalactam compounds as HPK1 inhibitors
CHEMBL6102709	IC50	115 nM
6-(dimethylamino)-4-(methylaminomethyl)-2-[6-(4-propyl-1,2,4-triazol-3-yl)-2-pyridinyl]-3H-pyrrolo[3,4-c]pyridin-1-one	IC50	121 nM	US-11142525: Azalactam compounds as HPK1 inhibitors
CHEMBL6149797	IC50	139 nM
4-[5-amino-6-[1-(1-methylpiperidin-4-yl)pyrazol-4-yl]oxypyrazin-2-yl]-N-[2-[(3R)-3-fluoropyrrolidin-1-yl]ethyl]-2,6-dimethylbenzamide	IC50	155 nM	US-20240317714: 3-[(1H-PYRAZOL-R-YL)OXY]PYRAZIN-2-AMINE COMPOUNDS AS HPK1 INHIBITOR AND USE THEREOF
3-[[1-(1-Cyano-1-methyl-ethyl)-3-methyl-pyrazol-4-yl]amino]-5-cyclopropyl-6-(3-methylimidazo[4,5-c]pyridin-7-yl)pyrazine-2-carboxamide	IC50	170 nM
3-[[1-(1-Cyanocyclopropyl)-3-methyl-pyrazol-4-yl]amino]-5-cyclopropyl-6-(3-methylimidazo[4,5-c]pyridin-7-yl)pyrazine-2-carboxamide	IC50	198 nM
CHEMBL6147154	IC50	222 nM
CHEMBL6108993	IC50	383 nM
CHEMBL6144977	IC50	520 nM
CHEMBL5419358	IC50	1040 nM
CHEMBL6091907	IC50	1070 nM
CHEMBL6150317	IC50	1080 nM
5-Methyl-6-(1-methylbenzimidazol-4-yl)-3-(4-morpholinoanilino)pyrazine-2-carboxamide	IC50	1200 nM

ChEMBL bioactivities

35 potent at pChembl≥5 of 35 total, top 34 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.05	IC50	9	nM	CHEMBL6133969
7.89	IC50	13	nM	CHEMBL6152052
7.77	IC50	17	nM	CHEMBL5860476
7.70	IC50	20	nM	CHEMBL6150979
7.50	IC50	32	nM	CHEMBL6160518
7.47	IC50	34	nM	CHEMBL5877890
7.43	IC50	37	nM	CHEMBL5969973
7.33	IC50	47	nM	CHEMBL5755922
7.33	IC50	47	nM	CHEMBL6144164
7.32	IC50	48	nM	CHEMBL6132870
7.28	IC50	52	nM	CHEMBL5826036
7.28	IC50	53	nM	CHEMBL5856381
7.28	IC50	53	nM	CHEMBL5842777
7.18	IC50	66	nM	CHEMBL6146353
7.16	IC50	70	nM	CHEMBL5848065
7.11	IC50	77	nM	CHEMBL6132909
7.09	IC50	81	nM	CHEMBL5936007
7.09	IC50	82	nM	CHEMBL6147087
7.06	IC50	87	nM	CHEMBL5902160
7.01	IC50	98	nM	CHEMBL6144058
6.95	IC50	112	nM	CHEMBL5759430
6.94	IC50	115	nM	CHEMBL6102709
6.92	IC50	121	nM	CHEMBL5897911
6.86	IC50	139	nM	CHEMBL6149797
6.81	IC50	155	nM	CHEMBL6148235
6.77	IC50	170	nM	CHEMBL6171777
6.70	IC50	198	nM	CHEMBL6133655
6.65	IC50	222	nM	CHEMBL6147154
6.42	IC50	383	nM	CHEMBL6108993
6.28	IC50	520	nM	CHEMBL6144977
5.98	IC50	1040	nM	CHEMBL5419358
5.97	IC50	1077	nM	CHEMBL6150317
5.97	IC50	1074	nM	CHEMBL6091907
5.92	IC50	1200	nM	CHEMBL6167391

PubChem BioAssay actives

35 with measured affinity, of 52 total; 34 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
5-cyclopropyl-6-(3-methylimidazo[4,5-c]pyridin-7-yl)-3-(4-morpholin-4-ylanilino)pyrazine-2-carboxamide	2233107: Inhibition of SLP76 phosphorylation in human T cells by alphaLISA assay	ic50	0.0090	uM
5-(methylamino)-6-(3-methylimidazo[4,5-c]pyridin-7-yl)-3-(4-morpholin-4-ylanilino)pyrazine-2-carboxamide	2233107: Inhibition of SLP76 phosphorylation in human T cells by alphaLISA assay	ic50	0.0130	uM
4-[(1R)-1-aminopropyl]-2-[6-[(5S)-5-methyl-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-3-yl]-2-pyridinyl]-6-[(2R)-2-methylpyrrolidin-1-yl]-3H-pyrrolo[3,4-c]pyridin-1-one	2211979: Inhibition of SLP76 phosphorylation at Ser376 in human Jurkat cells incubated for 30 mins by HTRF assay	ic50	0.0170	uM
5-methoxy-6-(3-methylimidazo[4,5-c]pyridin-7-yl)-3-(4-morpholin-4-ylanilino)pyrazine-2-carboxamide	2233107: Inhibition of SLP76 phosphorylation in human T cells by alphaLISA assay	ic50	0.0200	uM
5-(difluoromethyl)-6-(3-methylimidazo[4,5-c]pyridin-7-yl)-3-(4-morpholin-4-ylanilino)pyrazine-2-carboxamide	2233107: Inhibition of SLP76 phosphorylation in human T cells by alphaLISA assay	ic50	0.0320	uM
4-(methylaminomethyl)-6-[(2R)-2-methylpyrrolidin-1-yl]-2-[6-(4-propyl-1,2,4-triazol-3-yl)-2-pyridinyl]-3H-pyrrolo[3,4-c]pyridin-1-one	2211979: Inhibition of SLP76 phosphorylation at Ser376 in human Jurkat cells incubated for 30 mins by HTRF assay	ic50	0.0340	uM
2-[6-[(5S)-5-ethyl-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-3-yl]-2-pyridinyl]-4-(methylaminomethyl)-6-[methyl(propan-2-yl)amino]-3H-pyrrolo[3,4-c]pyridin-1-one	2211979: Inhibition of SLP76 phosphorylation at Ser376 in human Jurkat cells incubated for 30 mins by HTRF assay	ic50	0.0370	uM
3-(2-fluoro-4-morpholin-4-ylanilino)-5-(methylamino)-6-(3-methylimidazo[4,5-c]pyridin-7-yl)pyrazine-2-carboxamide	2233107: Inhibition of SLP76 phosphorylation in human T cells by alphaLISA assay	ic50	0.0470	uM
4-(methylaminomethyl)-2-[6-[(5S)-5-methyl-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-3-yl]-2-pyridinyl]-6-[methyl(propan-2-yl)amino]-3H-pyrrolo[3,4-c]pyridin-1-one	2211979: Inhibition of SLP76 phosphorylation at Ser376 in human Jurkat cells incubated for 30 mins by HTRF assay	ic50	0.0470	uM
5-cyclopropyl-3-[(1,3-dimethylpyrazol-4-yl)amino]-6-(3-methylimidazo[4,5-c]pyridin-7-yl)pyrazine-2-carboxamide	2233107: Inhibition of SLP76 phosphorylation in human T cells by alphaLISA assay	ic50	0.0480	uM
2-[6-[(5R)-5-(fluoromethyl)-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-3-yl]-2-pyridinyl]-4-(methylaminomethyl)-6-[methyl(propan-2-yl)amino]-3H-pyrrolo[3,4-c]pyridin-1-one	2211979: Inhibition of SLP76 phosphorylation at Ser376 in human Jurkat cells incubated for 30 mins by HTRF assay	ic50	0.0520	uM
4-[(1R)-1-aminoethyl]-2-[6-[(5S)-5-methyl-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-3-yl]-2-pyridinyl]-6-[(2R)-2-methylpyrrolidin-1-yl]-3H-pyrrolo[3,4-c]pyridin-1-one	2211979: Inhibition of SLP76 phosphorylation at Ser376 in human Jurkat cells incubated for 30 mins by HTRF assay	ic50	0.0530	uM
4-[(1R)-1-aminopropyl]-2-[6-(4-ethyl-1,2,4-triazol-3-yl)-2-pyridinyl]-6-[(2R)-2-methylpyrrolidin-1-yl]-3H-pyrrolo[3,4-c]pyridin-1-one	2211979: Inhibition of SLP76 phosphorylation at Ser376 in human Jurkat cells incubated for 30 mins by HTRF assay	ic50	0.0530	uM
5-methyl-6-(3-methylimidazo[4,5-c]pyridin-7-yl)-3-(4-morpholin-4-ylanilino)pyrazine-2-carboxamide	2233107: Inhibition of SLP76 phosphorylation in human T cells by alphaLISA assay	ic50	0.0660	uM
6-(dimethylamino)-4-(methylaminomethyl)-2-[6-[4-[(2S)-4,4,4-trifluorobutan-2-yl]-1,2,4-triazol-3-yl]-2-pyridinyl]-3H-pyrrolo[3,4-c]pyridin-1-one	2211979: Inhibition of SLP76 phosphorylation at Ser376 in human Jurkat cells incubated for 30 mins by HTRF assay	ic50	0.0700	uM
3-[(1,3-dimethylpyrazol-4-yl)amino]-5-(methylamino)-6-(3-methylimidazo[4,5-c]pyridin-7-yl)pyrazine-2-carboxamide	2233107: Inhibition of SLP76 phosphorylation in human T cells by alphaLISA assay	ic50	0.0770	uM
4-(methylaminomethyl)-6-[methyl(propan-2-yl)amino]-2-[6-(5-methyl-4-propyl-1,2,4-triazol-3-yl)-2-pyridinyl]-3H-pyrrolo[3,4-c]pyridin-1-one	2211979: Inhibition of SLP76 phosphorylation at Ser376 in human Jurkat cells incubated for 30 mins by HTRF assay	ic50	0.0810	uM
5-cyclopropyl-6-(3-methylimidazo[4,5-c]pyridin-7-yl)-3-[[3-methyl-1-(2,2,2-trifluoroethyl)pyrazol-4-yl]amino]pyrazine-2-carboxamide	2233107: Inhibition of SLP76 phosphorylation in human T cells by alphaLISA assay	ic50	0.0820	uM
4-(methylaminomethyl)-6-[methyl(propan-2-yl)amino]-2-[6-(4-propyl-1,2,4-triazol-3-yl)-2-pyridinyl]-3H-pyrrolo[3,4-c]pyridin-1-one	2211979: Inhibition of SLP76 phosphorylation at Ser376 in human Jurkat cells incubated for 30 mins by HTRF assay	ic50	0.0870	uM
5-cyclopropyl-3-[[1-(2,2-difluoroethyl)-3-methylpyrazol-4-yl]amino]-6-(3-methylimidazo[4,5-c]pyridin-7-yl)pyrazine-2-carboxamide	2233107: Inhibition of SLP76 phosphorylation in human T cells by alphaLISA assay	ic50	0.0980	uM
6-(dimethylamino)-4-(methylaminomethyl)-2-[6-(4-propan-2-yl-1,2,4-triazol-3-yl)-2-pyridinyl]-3H-pyrrolo[3,4-c]pyridin-1-one	2211979: Inhibition of SLP76 phosphorylation at Ser376 in human Jurkat cells incubated for 30 mins by HTRF assay	ic50	0.1120	uM
6-methoxy-4-(methylaminomethyl)-2-[6-[4-[(2S)-4,4,4-trifluorobutan-2-yl]-1,2,4-triazol-3-yl]-2-pyridinyl]-3H-isoindol-1-one	2211979: Inhibition of SLP76 phosphorylation at Ser376 in human Jurkat cells incubated for 30 mins by HTRF assay	ic50	0.1150	uM
6-(dimethylamino)-4-(methylaminomethyl)-2-[6-(4-propyl-1,2,4-triazol-3-yl)-2-pyridinyl]-3H-pyrrolo[3,4-c]pyridin-1-one	2211979: Inhibition of SLP76 phosphorylation at Ser376 in human Jurkat cells incubated for 30 mins by HTRF assay	ic50	0.1210	uM
2-(aminomethyl)-N-[6-[4-[(2S)-butan-2-yl]-1,2,4-triazol-3-yl]-2-pyridinyl]-1-methylbenzimidazole-4-carboxamide	2211979: Inhibition of SLP76 phosphorylation at Ser376 in human Jurkat cells incubated for 30 mins by HTRF assay	ic50	0.1390	uM
4-[5-amino-6-[1-(1-methylpiperidin-4-yl)pyrazol-4-yl]oxypyrazin-2-yl]-N-[2-[(3R)-3-fluoropyrrolidin-1-yl]ethyl]-2,6-dimethylbenzamide	2232477: Inhibition of SLP76 phosphorylation (unknown origin)	ic50	0.1550	uM
3-[[1-(2-cyanopropan-2-yl)-3-methylpyrazol-4-yl]amino]-5-cyclopropyl-6-(3-methylimidazo[4,5-c]pyridin-7-yl)pyrazine-2-carboxamide	2233107: Inhibition of SLP76 phosphorylation in human T cells by alphaLISA assay	ic50	0.1700	uM
3-[[1-(1-cyanocyclopropyl)-3-methylpyrazol-4-yl]amino]-5-cyclopropyl-6-(3-methylimidazo[4,5-c]pyridin-7-yl)pyrazine-2-carboxamide	2233107: Inhibition of SLP76 phosphorylation in human T cells by alphaLISA assay	ic50	0.1980	uM
3-amino-N-[6-(4-butan-2-yl-1,2,4-triazol-3-yl)-2-pyridinyl]-3,4-dihydro-2H-chromene-8-carboxamide	2211979: Inhibition of SLP76 phosphorylation at Ser376 in human Jurkat cells incubated for 30 mins by HTRF assay	ic50	0.2220	uM
6-methoxy-4-(methylaminomethyl)-2-[6-(4-propan-2-yl-1,2,4-triazol-3-yl)-2-pyridinyl]-3H-isoindol-1-one	2211979: Inhibition of SLP76 phosphorylation at Ser376 in human Jurkat cells incubated for 30 mins by HTRF assay	ic50	0.3830	uM
4-(aminomethyl)-5-methoxy-2-[6-[4-[(2S)-4,4,4-trifluorobutan-2-yl]-1,2,4-triazol-3-yl]-2-pyridinyl]-3H-isoindol-1-one	2211979: Inhibition of SLP76 phosphorylation at Ser376 in human Jurkat cells incubated for 30 mins by HTRF assay	ic50	0.5200	uM
2-[[2-[(6-methoxy-2-methyl-3,4-dihydro-1H-isoquinolin-7-yl)amino]-5-pyridin-3-yl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-N,N-dimethylbenzenesulfonamide	2232477: Inhibition of SLP76 phosphorylation (unknown origin)	ic50	1.0400	uM
2-(aminomethyl)-1-methyl-N-[6-(4-propan-2-yl-1,2,4-triazol-3-yl)-2-pyridinyl]benzimidazole-4-carboxamide	2211979: Inhibition of SLP76 phosphorylation at Ser376 in human Jurkat cells incubated for 30 mins by HTRF assay	ic50	1.0740	uM
3-amino-N-[6-(4-propan-2-yl-1,2,4-triazol-3-yl)-2-pyridinyl]-3,4-dihydro-2H-chromene-8-carboxamide	2211979: Inhibition of SLP76 phosphorylation at Ser376 in human Jurkat cells incubated for 30 mins by HTRF assay	ic50	1.0770	uM
5-methyl-6-(1-methylbenzimidazol-4-yl)-3-(4-morpholin-4-ylanilino)pyrazine-2-carboxamide	2233107: Inhibition of SLP76 phosphorylation in human T cells by alphaLISA assay	ic50	1.2000	uM

CTD chemical–gene interactions

33 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases expression, increases methylation, affects methylation	4
Tretinoin	affects cotreatment, increases reaction, increases phosphorylation, decreases reaction, increases expression	3
Valproic Acid	affects cotreatment, increases expression	3
Nickel	increases expression	2
triphenyl phosphate	affects expression	1
sodium arsenite	decreases expression	1
zomepirac glucuronide	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
tolmetin glucuronide	increases expression	1
tamibarotene	increases expression	1
di-n-butylphosphoric acid	affects expression	1
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Curcumin	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression	1
Methotrexate	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Ozone	increases abundance, increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	increases expression	1
T-2 Toxin	decreases expression	1
Vincristine	increases expression	1
Isotretinoin	increases expression	1
Aflatoxin B1	increases methylation	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL6081514	Binding	Inhibition of SLP76 phosphorylation at Ser376 in human Jurkat cells incubated for 30 mins by HTRF assay	Discovery of PF-07265028, A Selective Small Molecule Inhibitor of Hematopoietic Progenitor Kinase 1 (HPK1) for the Treatment of Cancer. — *J Med Chem*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for LCP2 across ~30M SureChEMBL compounds — explore on Sugi Predict.