LY96

Summary

LY96 (lymphocyte antigen 96, HGNC:17156) is a protein-coding gene on chromosome 8q21.11, encoding Lymphocyte antigen 96 (Q9Y6Y9). Binds bacterial lipopolysaccharide (LPS).

This gene encodes a protein which associates with toll-like receptor 4 on the cell surface and confers responsiveness to lipopolysaccyaride (LPS), thus providing a link between the receptor and LPS signaling. Studies of the mouse ortholog suggest that this gene may be involved in endotoxin neutralization. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 23643 — RefSeq curated summary.

At a glance

• Gene–disease (curated): inborn error of immunity (Limited, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 21 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_015364

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17156
Approved symbol	LY96
Name	lymphocyte antigen 96
Location	8q21.11
Locus type	gene with protein product
Status	Approved
Aliases	MD-2
Ensembl gene	ENSG00000154589
Ensembl biotype	protein_coding
OMIM	605243
Entrez	23643

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000284818, ENST00000518893, ENST00000962532

RefSeq mRNA: 2 — MANE Select: NM_015364 NM_001195797, NM_015364

CCDS: CCDS56540, CCDS6216

Canonical transcript exons

ENST00000284818 — 5 exons

Exon	Start	End
ENSE00001016734	74026789	74026841
ENSE00001016736	74010001	74010129
ENSE00001016737	74004796	74004885
ENSE00001244306	73991392	73991554
ENSE00002121776	74028956	74029079

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 97.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.7551 / max 844.9121, expressed in 1270 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
89394	22.8565	1260
89396	1.4543	473
89395	0.4443	186

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	97.94	gold quality
mononuclear cell	CL:0000842	97.89	gold quality
leukocyte	CL:0000738	97.83	gold quality
periodontal ligament	UBERON:0008266	96.64	gold quality
granulocyte	CL:0000094	95.54	gold quality
spleen	UBERON:0002106	95.53	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.40	gold quality
vermiform appendix	UBERON:0001154	92.69	gold quality
lymph node	UBERON:0000029	92.41	gold quality
gall bladder	UBERON:0002110	92.35	gold quality
decidua	UBERON:0002450	92.11	gold quality
trabecular bone tissue	UBERON:0002483	91.45	gold quality
pericardium	UBERON:0002407	91.36	gold quality
omental fat pad	UBERON:0010414	90.31	gold quality
superficial temporal artery	UBERON:0001614	90.28	gold quality
peritoneum	UBERON:0002358	90.28	gold quality
right coronary artery	UBERON:0001625	90.27	gold quality
adipose tissue of abdominal region	UBERON:0007808	89.96	gold quality
bone marrow	UBERON:0002371	88.81	gold quality
blood	UBERON:0000178	88.78	gold quality
descending thoracic aorta	UBERON:0002345	88.76	gold quality
lower lobe of lung	UBERON:0008949	87.81	gold quality
right lung	UBERON:0002167	87.67	gold quality
stromal cell of endometrium	CL:0002255	87.45	gold quality
layer of synovial tissue	UBERON:0007616	87.43	gold quality
thoracic aorta	UBERON:0001515	87.42	gold quality
ascending aorta	UBERON:0001496	87.37	gold quality
left coronary artery	UBERON:0001626	87.31	gold quality
calcaneal tendon	UBERON:0003701	87.24	gold quality
upper lobe of lung	UBERON:0008948	87.05	gold quality

Single-cell (SCXA)

Detected in 15 experiment(s), a significant marker in 15.

Experiment	Marker?	Max mean expression
E-GEOD-81383	yes	231.81
E-MTAB-6701	yes	86.40
E-CURD-88	yes	85.50
E-HCAD-1	yes	83.96
E-HCAD-10	yes	54.08
E-MTAB-8410	yes	50.14
E-HCAD-4	yes	39.23
E-CURD-46	yes	33.52
E-MTAB-10553	yes	29.64
E-MTAB-10287	yes	23.08
E-HCAD-9	yes	21.62
E-HCAD-11	yes	18.81
E-CURD-112	yes	18.06
E-ANND-3	yes	13.91
E-MTAB-6678	yes	11.21

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, CREB5, ELK1, HAND1, IRF6, NFKB, RELA, SPI1, STAT1, TXK

Literature-anchored findings (GeneRIF, showing 40)

• Expression of accessory molecule MD-2 is downregulated in intestinal epithelial cells by a mechanism which limits dysregulated immune signaling and activation of proinflammatory genes in response to bacterial lipopolysaccharide. (PMID:11466383)
• MD-2 can confer on mouse Toll-like receptor 4 (TLR4) responsiveness to lipid A but not to lipid IVa, thus influencing the fine specificity of TLR4. (PMID:11717200)
• expression regulated by immune-mediated signals in intestinal epithelial cells (PMID:11923281)
• Lipopolysaccharide rapidly traffics to and from the Golgi apparatus with the toll-like receptor 4-MD-2-CD14 complex (PMID:12324469)
• innate immune recognition of LTA via LBP, CD14, and TLR-2 represents an important mechanism in the pathogenesis of systemic complications in the course of infectious diseases brought about by Gram-positive pathogens. while TLR-4 and MD-2 are not involved. (PMID:12594207)
• Disulfide bonds are involved in the assembly and fuction of this protein. (PMID:12642668)
• TLR4 is able to undergo multiple glycosylations without MD-2 but that the specific glycosylation essential for cell surface expression requires the presence of MD-2. (PMID:12738639)
• data support the hypothesis that lipopolysaccharide binding protein can inhibit cell responses to lipopolysaccharide(LPS) by inhibiting LPS transfer from membrane CD14 to the Toll-like receptor 4-MD-2 signaling receptor (PMID:12754215)
• MD-2 binds to lipopolysaccharide, leading to Toll-like receptor-4 aggregation and signal transduction (PMID:12960171)
• Two functional domains exist in MD-2, one responsible for Toll-like receptor 4-binding and another that mediates the interaction with the agonist (lipopolysaccharide). (PMID:14607928)
• a rare A –> G substitution at position 103, Thr 35 to Ala, results in a reduced lipopolysaccharide-induced signaling. (PMID:15057266)
• MD-2 basic amino acid clusters are involved in cellular lipopolysaccharide recognition (PMID:15111623)
• The regulation of MD-2 expression in airway epithelia and pulmonary macrophages may serve as a means to modify endotoxin responsiveness in the airway. (PMID:15121639)
• MD-2 is an important mediator of organ inflammation during sepsis. (PMID:15328161)
• Results show that the N-terminal region of toll-like receptor 4 is essential for association with MD-2, which is required for the cell surface expression and hence the responsiveness to lipopolysaccharide. (PMID:15337750)
• The extracellular toll-like receptor 4 (TLR4)domain-MD-2 complex is capable of binding lipopolysaccharide (LPS) and attenuating LPS-induced NF-kappa B activation and IL-8 secretion in wild-type TLR4-expressing cells. (PMID:15557191)
• These results clearly demonstrate that the amino-terminal TLR4 region of Glu(24)-Pro(34) is critical for MD-2 binding and LPS signaling. (PMID:15694388)
• MD-2 is the primary molecular site of lipopolysaccharide(LPS)-dependent antagonism of Escherichia coli LPS at the Toll-like receptor 4 signaling complex (PMID:16177092)
• The lipopolysaccharide-binding function characteristic of MD-2 enables effective host responses to pathogens. (PMID:16275943)
• A PRotein Associated with Tlr4 (PRAT4B), regulates cell surface expression of TLR4. PRAT4B has a signal peptide followed by a mature peptide. PRAT4B is associated with the hypoglycosylated, immature form of TLR4 but not with MD-2 or TLR2. (PMID:16338228)
• endoplasmic reticulum-associated MD-2 expression in inflammatory bowel disease may be altered by ileal protease in inflammation, leading to impaired lipopolysaccharide recognition and hyporesponsiveness through MD-2 proteolysis in epithelial cell (PMID:16547263)
• SP-A bound to sTLR4 and MD-2 in a Ca2+-dependent manner, and involved the carbohydrate recognition domain (CRD) in the binding. SP-A avidly bound to the deglycosylated forms of sTLR4 and MD-2, suggesting a protein/protein interaction. (PMID:16754682)
• New insights are provided into the importance of stoichiometry among the components of the TLR4/MD-2/CD14 complex; transfected MD-2 at high input levels often used in the literature suppresses lipopolysaccharide-induced signaling. (PMID:16785528)
• The structural pattern recognized by MD-2 is defined by the hydrophobic patch and a pair of separated negative charges. (PMID:16940155)
• Human conjunctival epithelial cells lack LPS responsiveness due to deficient expression of MD2. (PMID:17093906)
• Butyrate dowregulates TLR4 mRNA without affecting MD-2 mRNA level in HT-29 cells. (PMID:17404865)
• MD-2 interacts with lipid A of endotoxins [lipopolysaccharide (LPS) or lipooligosaccharide (LOS)] to activate human toll-like receptor (TLR) 4 (PMID:17545685)
• crystal structures of MD-2 and its complex with tetra-acylated lipid A core of LPS were determined at 2.0 and 2.2 angstrom resolutions, respectively; these structures suggest that MD-2 plays a principal role in endotoxin recognition (PMID:17569869)
• The MD-2/-1625 polymorphism is an important functional variant. (PMID:17592304)
• Based on structural analysis and mutagenesis experiments on MD-2 and TLR4, we propose a model of TLR4-MD-2 dimerization induced by LPS. (PMID:17803912)
• Transfer of endotoxin from MD-2 to extracellular soluble CD14 reduces activation of cells expressing TLR4 without MD-2. (PMID:17934216)
• TLR4/MD-2 complex is responsible for recognition of Rhodococcus spheroides lipopolysaccharide as an agonist in human cells. (PMID:17956942)
• These findings strongly suggest that the structural properties of (endotoxin) E.MD-2, not E alone, determine agonist or antagonist effects on TLR4. (PMID:17977838)
• ERK and JNK pathways are involved in PMA-mediated MD-2 gene expression during HL-60 cell differentiation. (PMID:18181766)
• Results show that LPS responsiveness increased more than 100-fold when intestinal epithelial cells were transfected with MD-2 alone. (PMID:18215718)
• MD-2 expression in human antral and corpus gastric mucosa is significantly increased during H. pylori infection (PMID:18251133)
• This study demonstrates the increase of both circulating polymeric and functional monomeric sMD-2 during endotoxemia and sepsis, and evidence is provided that the endothelium is involved in this process. (PMID:18384879)
• cells that express TLR4 without MD-2 and whose response to LPS depends on ectopically produced MD-2 were most affected by expression of the G56R variant of MD-2. (PMID:18424732)
• the monomeric form of sMD-2 is the active species both for reaction with endotoxin.CD14 and Toll-like receptor 4 (TLR4), as needed for potent endotoxin-induced TLR4 activation (PMID:18519568)
• Oxidized phospholipid inhibition of toll-like receptor (TLR) signaling is restricted to TLR2 and TLR4: roles for CD14, LPS-binding protein, and MD2 as targets for specificity of inhibition. (PMID:18559343)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ly96	ENSMUSG00000025779
rattus_norvegicus	Ly96	ENSRNOG00000067966

Protein

Protein identifiers

Lymphocyte antigen 96 — Q9Y6Y9 (reviewed: Q9Y6Y9)

Alternative names: ESOP-1, Protein MD-2

All UniProt accessions (1): Q9Y6Y9

UniProt curated annotations — full annotation on UniProt →

Function. Binds bacterial lipopolysaccharide (LPS). Cooperates with TLR4 in the innate immune response to bacterial lipopolysaccharide (LPS), and with TLR2 in the response to cell wall components from Gram-positive and Gram-negative bacteria. Enhances TLR4-dependent activation of NF-kappa-B. Cells expressing both LY96 and TLR4, but not TLR4 alone, respond to LPS.

Subunit / interactions. Heterogeneous homomer formed from homodimers; disulfide-linked. Belongs to the lipopolysaccharide (LPS) receptor, a multi-protein complex containing at least CD14, LY96 and TLR4. Binds to the extracellular domains of TLR2 and TLR4. Ligand binding induces interaction with TLR4 and oligomerization of the complex.

Subcellular location. Secreted. Extracellular space.

Post-translational modifications. N-glycosylated; high-mannose.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y6Y9-1	1	yes
Q9Y6Y9-2	2

RefSeq proteins (2): NP_001182726, NP_056179* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003172	ML_dom	Domain
IPR014756	Ig_E-set	Homologous_superfamily
IPR039217	LY96	Family

Pfam: PF02221

UniProt features (25 total): strand 11, disulfide bond 3, sequence variant 2, glycosylation site 2, signal peptide 1, chain 1, mutagenesis site 1, region of interest 1, helix 1, turn 1, splice variant 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
2E56	X-RAY DIFFRACTION	2
2E59	X-RAY DIFFRACTION	2.21
8WO1	ELECTRON MICROSCOPY	2.24
4G8A	X-RAY DIFFRACTION	2.4
2Z65	X-RAY DIFFRACTION	2.7
9J03	ELECTRON MICROSCOPY	2.7
8WTA	ELECTRON MICROSCOPY	2.9
3FXI	X-RAY DIFFRACTION	3.1
3ULA	X-RAY DIFFRACTION	3.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y6Y9-F1	87.74	0.67

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): 25–51, 37–148, 95–105

Glycosylation sites (2): 26, 114

Mutagenesis-validated functional residues (1):

Position	Phenotype
95	abolishes lps-response.

Function

Pathways and Gene Ontology

Reactome pathways

43 pathways

ID	Pathway
R-HSA-1236974	ER-Phagosome pathway
R-HSA-140534	Caspase activation via Death Receptors in the presence of ligand
R-HSA-166016	Toll Like Receptor 4 (TLR4) Cascade
R-HSA-166058	MyD88:MAL(TIRAP) cascade initiated on plasma membrane
R-HSA-166166	MyD88-independent TLR4 cascade
R-HSA-2562578	TRIF-mediated programmed cell death
R-HSA-5602498	MyD88 deficiency (TLR2/4)
R-HSA-5603041	IRAK4 deficiency (TLR2/4)
R-HSA-5686938	Regulation of TLR by endogenous ligand
R-HSA-936964	Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE)
R-HSA-937041	IKK complex recruitment mediated by RIP1
R-HSA-937072	TRAF6-mediated induction of TAK1 complex within TLR4 complex
R-HSA-9707616	Heme signaling
R-HSA-975163	IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation
R-HSA-9820960	Respiratory syncytial virus (RSV) attachment and entry
R-HSA-9824878	Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7
R-HSA-9833110	RSV-host interactions
R-HSA-9918481	Dengue Virus-Host Interactions
R-HSA-109581	Apoptosis
R-HSA-1236975	Antigen processing-Cross presentation
R-HSA-1280218	Adaptive Immune System
R-HSA-1643685	Disease
R-HSA-168138	Toll Like Receptor 9 (TLR9) Cascade
R-HSA-168179	Toll Like Receptor TLR1:TLR2 Cascade
R-HSA-168181	Toll Like Receptor 7/8 (TLR7/8) Cascade
R-HSA-168188	Toll Like Receptor TLR6:TLR2 Cascade
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-168898	Toll-like Receptor Cascades
R-HSA-181438	Toll Like Receptor 2 (TLR2) Cascade

MSigDB gene sets: 282 (showing top): REACTOME_TRAF6_MEDIATED_INDUCTION_OF_TAK1_COMPLEX_WITHIN_TLR4_COMPLEX, REACTOME_IKK_COMPLEX_RECRUITMENT_MEDIATED_BY_RIP1, DAVIES_MULTIPLE_MYELOMA_VS_MGUS_DN, WALLACE_PROSTATE_CANCER_RACE_UP, REACTOME_INNATE_IMMUNE_SYSTEM, MCLACHLAN_DENTAL_CARIES_UP, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_CELLULAR_RESPONSE_TO_LIPID, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, MODULE_45, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, RIZKI_TUMOR_INVASIVENESS_3D_DN, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND

GO Biological Process (14): toll-like receptor signaling pathway (GO:0002224), inflammatory response (GO:0006954), cellular defense response (GO:0006968), cell surface receptor signaling pathway (GO:0007166), positive regulation of lipopolysaccharide-mediated signaling pathway (GO:0031666), response to lipopolysaccharide (GO:0032496), detection of lipopolysaccharide (GO:0032497), positive regulation of tumor necrosis factor production (GO:0032760), toll-like receptor 4 signaling pathway (GO:0034142), innate immune response (GO:0045087), cellular response to lipopolysaccharide (GO:0071222), pattern recognition receptor signaling pathway (GO:0002221), immune system process (GO:0002376), lipopolysaccharide-mediated signaling pathway (GO:0031663)

GO Molecular Function (5): lipopolysaccharide binding (GO:0001530), lipopolysaccharide immune receptor activity (GO:0001875), coreceptor activity (GO:0015026), Toll-like receptor 4 binding (GO:0035662), protein binding (GO:0005515)

GO Cellular Component (5): extracellular region (GO:0005576), plasma membrane (GO:0005886), endosome membrane (GO:0010008), signaling receptor complex (GO:0043235), lipopolysaccharide receptor complex (GO:0046696)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
TRIF (TICAM1)-mediated TLR4 signaling	4
Toll-like Receptor Cascades	2
Toll Like Receptor 4 (TLR4) Cascade	2
Diseases associated with the TLR signaling cascade	2
Respiratory Syncytial Virus Infection Pathway	2
Antigen processing-Cross presentation	1
Caspase activation via extrinsic apoptotic signalling pathway	1
Toll Like Receptor TLR1:TLR2 Cascade	1
Toll Like Receptor TLR6:TLR2 Cascade	1
Cellular responses to stress	1
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation	1
Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE)	1
Dengue Virus Infection	1
Programmed Cell Death	1
Class I MHC mediated antigen processing & presentation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
defense response	2
lipopolysaccharide-mediated signaling pathway	2
response to lipopolysaccharide	2
pattern recognition receptor signaling pathway	1
signal transduction	1
positive regulation of response to biotic stimulus	1
positive regulation of signal transduction	1
regulation of lipopolysaccharide-mediated signaling pathway	1
positive regulation of response to external stimulus	1
response to molecule of bacterial origin	1
response to lipid	1
response to oxygen-containing compound	1
detection of molecule of bacterial origin	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
positive regulation of tumor necrosis factor superfamily cytokine production	1
cell surface toll-like receptor signaling pathway	1
immune response	1
defense response to symbiont	1
cellular response to molecule of bacterial origin	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
innate immune response-activating signaling pathway	1
biological_process	1
cell surface receptor signaling pathway	1
cellular response to lipopolysaccharide	1
lipid binding	1
carbohydrate derivative binding	1
lipopolysaccharide binding	1
pattern recognition receptor activity	1
signaling receptor activity	1
Toll-like receptor binding	1
binding	1
cellular anatomical structure	1
membrane	1
cell periphery	1
endosome	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

1972 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LY96	TLR4	O00206	999
LY96	TLR2	O60603	992
LY96	MYD88	P78397	992
LY96	LY86	O95711	989
LY96	LBP	P18428	960
LY96	CD44	P16070	960
LY96	HMGB1	P09429	917
LY96	GHITM	Q9H3K2	910
LY96	TLR1	Q15399	883
LY96	CNPY3	Q9BT09	878
LY96	TLR5	O60602	863
LY96	CD180	Q99467	861
LY96	IRAK1	P51617	855
LY96	CNPY4	Q8N129	828
LY96	TIRAP	P58753	815
LY96	TRAF6	Q9Y4K3	815

IntAct

26 interactions, top by confidence:

A	B	Type	Score
TLR4	LY96	psi-mi:“MI:0915”(physical association)	0.820
LY96	TLR4	psi-mi:“MI:0407”(direct interaction)	0.820
TLR4	LY96	psi-mi:“MI:0407”(direct interaction)	0.820
LY96	TLR4	psi-mi:“MI:0915”(physical association)	0.740
TLR4	LY96	psi-mi:“MI:0915”(physical association)	0.740
TLR4	HMGB1	psi-mi:“MI:0915”(physical association)	0.600
LCN2	LY96	psi-mi:“MI:0915”(physical association)	0.560
MESD	LY96	psi-mi:“MI:0915”(physical association)	0.560
	LY96	psi-mi:“MI:0407”(direct interaction)	0.440
TLR4	Hmgb1	psi-mi:“MI:0915”(physical association)	0.400
	LY96	psi-mi:“MI:0915”(physical association)	0.400
DERP2	LY96	psi-mi:“MI:0915”(physical association)	0.400
LY96	LY86	psi-mi:“MI:0915”(physical association)	0.400
LY96	MLH1	psi-mi:“MI:0915”(physical association)	0.370
LY96	SMARCB1	psi-mi:“MI:0915”(physical association)	0.370
CDKN2C	LY96	psi-mi:“MI:0915”(physical association)	0.370
LY96	LCN2	psi-mi:“MI:0915”(physical association)	0.000
LY96	MESD	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (9): LY96 (Two-hybrid), LY96 (Two-hybrid), LY96 (Two-hybrid), LY96 (Two-hybrid), TLR4 (Affinity Capture-Western), LY96 (Affinity Capture-Western), LY96 (Affinity Capture-Western), LY96 (Reconstituted Complex), LY96 (Two-hybrid)

ESM2 similar proteins: A0A1S4GYH9, A0A1S4HDQ2, A0NAZ8, A0NBD9, A1EA99, B0FHH8, B0WS18, B4GJ61, B4KG03, G3CJS0, O17271, O18016, O55159, O88188, O95711, P16422, P20797, P34174, P49273, P49278, P58754, P58755, Q00855, Q09276, Q17077, Q17078, Q17FF6, Q1WER1, Q26456, Q27042, Q29JT7, Q3T0L5, Q45KX2, Q5F381, Q6FNB1, Q6PQK2, Q7PZ66, Q8WPC2, Q90890, Q93796

Diamond homologs: P58754, P58755, Q9JHF9, Q9Y6Y9

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
CREB5	“down-regulates quantity by repression”	LY96	“transcriptional regulation”
LY96	“up-regulates activity”	HMGB1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	11
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1456580	NC_000008.10:g.(?74890971)(74903809_?)del	Pathogenic

SpliceAI

740 predictions. Top by Δscore:

Variant	Effect	Δscore
8:74009995:TTAAA:T	acceptor_loss	1.0000
8:74009997:AAAG:A	acceptor_gain	1.0000
8:74009999:A:AG	acceptor_gain	1.0000
8:74010000:G:GG	acceptor_gain	1.0000
8:74010000:GGGA:G	acceptor_gain	1.0000
8:74010125:GGGAG:G	donor_gain	1.0000
8:74010126:GGAG:G	donor_gain	1.0000
8:74010126:GGAGG:G	donor_gain	1.0000
8:74010127:GAG:G	donor_gain	1.0000
8:74010127:GAGG:G	donor_gain	1.0000
8:74010128:AG:A	donor_gain	1.0000
8:74010128:AGG:A	donor_loss	1.0000
8:74010129:GG:G	donor_gain	1.0000
8:74010129:GGTA:G	donor_loss	1.0000
8:74010130:G:C	donor_loss	1.0000
8:74010130:G:GG	donor_gain	1.0000
8:74010131:T:G	donor_loss	1.0000
8:74009997:A:AG	acceptor_gain	0.9900
8:74009998:A:G	acceptor_gain	0.9900
8:74009998:AAG:A	acceptor_gain	0.9900
8:74009999:AG:A	acceptor_gain	0.9900
8:74010000:GG:G	acceptor_gain	0.9900
8:74010035:T:G	acceptor_gain	0.9900
8:74010037:T:G	acceptor_gain	0.9900
8:74010127:G:T	donor_gain	0.9900
8:74026787:A:AG	acceptor_gain	0.9900
8:74026788:G:GG	acceptor_gain	0.9900
8:74008520:A:T	donor_gain	0.9800
8:74009997:AAAGG:A	acceptor_gain	0.9800
8:74009999:AGG:A	acceptor_gain	0.9800

AlphaMissense

1050 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:74010081:T:A	C95S	0.987
8:74010082:G:C	C95S	0.987
8:74010081:T:C	C95R	0.984
8:74010111:T:A	C105S	0.982
8:74010112:G:C	C105S	0.982
8:74028980:G:C	A137P	0.980
8:74010111:T:C	C105R	0.977
8:73991515:T:A	C25S	0.975
8:73991516:G:C	C25S	0.975
8:74010112:G:A	C105Y	0.975
8:74029015:C:G	C148W	0.974
8:74010082:G:A	C95Y	0.973
8:73991515:T:C	C25R	0.971
8:74010083:C:G	C95W	0.971
8:74010067:G:C	R90P	0.964
8:74028968:T:C	C133R	0.964
8:74028981:C:A	A137D	0.963
8:74010113:C:G	C105W	0.962
8:74029014:G:A	C148Y	0.962
8:74029013:T:C	C148R	0.960
8:74028962:T:G	Y131D	0.959
8:73991516:G:A	C25Y	0.958
8:74010125:G:C	K109N	0.955
8:74010125:G:T	K109N	0.955
8:73991551:T:A	C37S	0.949
8:73991552:G:C	C37S	0.949
8:73991517:C:G	C25W	0.948
8:74004834:T:C	C51R	0.947
8:74010112:G:T	C105F	0.947
8:73991552:G:A	C37Y	0.946

dbSNP variants (sampled 300 via entrez): RS1000003109 (8:74030296 T>C), RS1000035964 (8:74024718 T>A,C), RS1000057015 (8:74024286 G>A), RS1000060019 (8:74063638 A>C,G), RS1000082970 (8:74036049 G>A), RS1000095633 (8:74018011 A>G,T), RS1000109375 (8:73994668 G>A), RS1000197099 (8:73999093 C>T), RS1000215450 (8:74027193 G>A), RS1000218194 (8:74066746 G>A), RS1000240057 (8:74058629 C>T), RS1000253710 (8:74040709 T>G), RS1000284791 (8:74040439 T>C), RS1000351738 (8:74052850 T>C), RS1000365249 (8:74078452 A>C,G)

Disease associations

OMIM: gene MIM:605243 | disease phenotypes: MIM:614052, MIM:214400

GenCC curated gene-disease

Disease	Classification	Inheritance
inborn error of immunity	Limited	Autosomal recessive

Mondo (3): mitochondrial complex V (ATP synthase) deficiency, nuclear type 2 (MONDO:0013546), Charcot-Marie-Tooth disease type 4A (MONDO:0008961), inborn error of immunity (MONDO:0003778)

Orphanet (2): TMEM70-related mitochondrial encephalo-cardio-myopathy (Orphanet:1194), Charcot-Marie-Tooth disease type 4A (Orphanet:99948)

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002482_3	Carotid plaque burden (smoking interaction)	5.000000e-06
GCST002975_2	Postoperative atrial fibrillation in coronary artery bypass grafting surgery	4.000000e-06
GCST008477_29	Emphysema annual change measurement in smokers (adjusted lung density)	3.000000e-06
GCST90013406_36	Liver enzyme levels (alkaline phosphatase)	8.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006501	carotid plaque build
EFO:0007626	emphysema imaging measurement
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D007153	Immunologic Deficiency Syndromes	C20.673
C535419	Charcot-Marie-Tooth disease, Type 4A (supp.)
C567528	Encephalocardiomyopathy, Mitochondrial, Neonatal, Due To Atp Synthase Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2375202 (SINGLE PROTEIN), CHEMBL3038512 (PROTEIN COMPLEX), CHEMBL3038513 (PROTEIN COMPLEX), CHEMBL4106126 (PROTEIN-PROTEIN INTERACTION)

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs11465996	Efficacy	3	Tumor necrosis factor alpha (TNF-alpha) inhibitors	Psoriasis

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs11465996	LY96	3	3.25	1	Tumor necrosis factor alpha (TNF-alpha) inhibitors
rs11466004	LY96		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — Lymphocyte antigens

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
L6H21	Inhibition	4.48	pKd

ChEMBL bioactivities

14 potent at pChembl≥5 of 25 total, top 14 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.75	Kd	180	nM	CHEMBL5084731
6.70	IC50	200	nM	CHEMBL4072822
6.24	Kd	570	nM	CHEMBL5076109
6.19	Kd	650	nM	CHEMBL4125910
6.16	IC50	700	nM	CHEMBL4081306
5.52	Kd	3000	nM	CHEMBL4100044
5.50	Kd	3200	nM	CHEMBL5075055
5.44	Kd	3600	nM	CHEMBL3601750
5.38	IC50	4220	nM	CHEMBL4176576
5.24	IC50	5700	nM	CHEMBL4105554
5.22	Kd	5950	nM	CHEMBL4125967
5.17	IC50	6830	nM	CHEMBL4164940
5.04	IC50	9080	nM	CHEMBL4162528
5.00	IC50	1e+04	nM	CHEMBL4093531

PubChem BioAssay actives

14 with measured affinity, of 209 total; 14 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
disodium;[(2R,3R,4R,5S,6R)-6-(hydroxymethyl)-3-(tetradecanoylamino)-4,5-di(tetradecanoyloxy)oxan-2-yl] phosphate	1809155: Binding affinity to NTA sensor chip immobilized recombinant human TLR4/MD2 assessed as dissociation constant by surface plasmon resonance analysis	kd	0.1800	uM
2-[4-[[5,11,17,23-tetratert-butyl-26,27,28-tris[4-(diaminomethylideneamino)butoxy]-25-pentacyclo[19.3.1.13,7.19,13.115,19]octacosa-1(24),3,5,7(28),9,11,13(27),15(26),16,18,21(25),22-dodecaenyl]oxy]butyl]guanidine;tetrahydrochloride	1447912: Binding affinity to CD14/MD2 (unknown origin) expressed in HEK-Blue cells co-expressing TLR4 assessed as inhibition of LPS-induced TLR4 signaling preincubated for 30 mins followed by LPS stimulation measured after overnight incubation by secreted embryonic alkaline phosphatase reporter gene assay	ic50	0.2000	uM
disodium;[(2R,3R,4R,5S,6R)-3-(dodecanoylamino)-4,5-di(dodecanoyloxy)-6-(hydroxymethyl)oxan-2-yl] phosphate	1809155: Binding affinity to NTA sensor chip immobilized recombinant human TLR4/MD2 assessed as dissociation constant by surface plasmon resonance analysis	kd	0.5700	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-phenylpropanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]pentanedioic acid	1494170: Binding affinity to human MD-2 (17 to 160 residues) assessed as reduction in MD-2 binding to human HMGB1 after 7 mins by SPR assay	kd	0.6500	uM
2-[11,17,23-tris(diaminomethylideneamino)-25,26,27-tripropoxy-5-pentacyclo[19.3.1.13,7.19,13.115,19]octacosa-1(25),3(28),4,6,9(27),10,12,15,17,19(26),21,23-dodecaenyl]guanidine;tetrahydrochloride	1447912: Binding affinity to CD14/MD2 (unknown origin) expressed in HEK-Blue cells co-expressing TLR4 assessed as inhibition of LPS-induced TLR4 signaling preincubated for 30 mins followed by LPS stimulation measured after overnight incubation by secreted embryonic alkaline phosphatase reporter gene assay	ic50	0.7000	uM
[(2R,3S,4R,5R,6R)-2-(hydroxymethyl)-3,6-diphosphonooxy-5-(tetradecanoylamino)oxan-4-yl] tetradecanoate	1455594: Binding to C-terminal His6-tagged human MD2 expressed in Pichia pastoris GS115 by surface plasmon resonance assay	kd	3.0000	uM
[(3E)-2-hydroxy-3-[[4-(trifluoromethyl)phenyl]methylidene]cyclohexen-1-yl]-phenylmethanone	1832927: Binding affinity to MD2 (unknown origin) assessed as dissociation constant by spectrofluorimetric analysis	kd	3.2000	uM
[(3E)-2-hydroxy-3-[(2,3,4-trimethoxyphenyl)methylidene]cyclohexen-1-yl]-phenylmethanone	1832927: Binding affinity to MD2 (unknown origin) assessed as dissociation constant by spectrofluorimetric analysis	kd	3.6000	uM
(1E,4E)-1-(3-bromo-4-hydroxyphenyl)-5-(2-methoxyphenyl)penta-1,4-dien-3-one	1501517: Displacement of bis-ANS to recombinant human MD2 after 5 mins by fluorescence assay	ic50	4.2200	uM
2-[11,17,23-tris(diaminomethylideneamino)-25,26,27-trihexoxy-5-pentacyclo[19.3.1.13,7.19,13.115,19]octacosa-1(25),3(28),4,6,9(27),10,12,15,17,19(26),21,23-dodecaenyl]guanidine;tetrahydrochloride	1447912: Binding affinity to CD14/MD2 (unknown origin) expressed in HEK-Blue cells co-expressing TLR4 assessed as inhibition of LPS-induced TLR4 signaling preincubated for 30 mins followed by LPS stimulation measured after overnight incubation by secreted embryonic alkaline phosphatase reporter gene assay	ic50	5.7000	uM
(3S)-3-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-aminopropanoyl]amino]-4-methylsulfanylbutanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]-4-[[(2R)-1-[[(2S)-1-[[(2S)-5-carbamimidamido-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-5-carbamimidamido-1-[[(2S)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-(carboxymethylamino)-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxo-3-sulfanylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxo-3-sulfanylpropan-2-yl]amino]-4-oxobutanoic acid	1494169: Binding affinity to recombinant human 10His-tagged TLR4 (24 to 631 residues)/recombinant human 10His-tagged MD2 (17 to 160 residues) after 5 mins by SPR assay	kd	5.9500	uM
(1E,4E)-1-(3-bromo-4-hydroxyphenyl)-5-(2,3-dimethoxyphenyl)penta-1,4-dien-3-one	1501517: Displacement of bis-ANS to recombinant human MD2 after 5 mins by fluorescence assay	ic50	6.8300	uM
(1E,4E)-1-(2-bromophenyl)-5-(2-methoxyphenyl)penta-1,4-dien-3-one	1501517: Displacement of bis-ANS to recombinant human MD2 after 5 mins by fluorescence assay	ic50	9.0800	uM
2-[3-[[5,11,17,23-tetratert-butyl-26,27,28-tris[3-(diaminomethylideneamino)propoxy]-25-pentacyclo[19.3.1.13,7.19,13.115,19]octacosa-1(24),3,5,7(28),9,11,13(27),15(26),16,18,21(25),22-dodecaenyl]oxy]propyl]guanidine;tetrahydrochloride	1447912: Binding affinity to CD14/MD2 (unknown origin) expressed in HEK-Blue cells co-expressing TLR4 assessed as inhibition of LPS-induced TLR4 signaling preincubated for 30 mins followed by LPS stimulation measured after overnight incubation by secreted embryonic alkaline phosphatase reporter gene assay	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation, affects methylation	6
Cyclosporine	increases expression, affects cotreatment	6
bisphenol A	decreases methylation, increases expression, affects binding, affects cotreatment	4
Lipopolysaccharides	affects binding, decreases reaction, increases expression, decreases response to substance, increases reaction (+1 more)	4
sodium arsenite	increases expression	3
Arsenic Trioxide	affects cotreatment, increases expression	3
Acetaminophen	decreases expression, affects cotreatment	3
Silicon Dioxide	increases expression	3
Aflatoxin B1	affects expression, increases expression	3
1-(3,4-dihydroxyphenyl)-3-(2-methoxyphenyl)prop-2-en-1-one	affects binding, decreases reaction, increases reaction	2
Vehicle Emissions	affects cotreatment, increases expression, affects expression, increases reaction	2
Formaldehyde	increases expression	2
Paraquat	increases expression	2
tert-Butylhydroperoxide	increases phosphorylation, increases reaction, increases expression, increases secretion, affects binding (+4 more)	2
Particulate Matter	decreases expression, increases abundance, affects expression, increases reaction	2
Asian ginseng	decreases expression, decreases reaction	1
methyleugenol	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
sodium arsenate	increases abundance, increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	increases expression	1
arsenite	increases reaction, affects binding	1
sodium bichromate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	affects binding, increases activity	1
butyraldehyde	increases expression	1
nickel chloride	affects binding, increases activity	1
zinc chromate	increases abundance, increases expression	1
tobacco tar	decreases expression	1

ChEMBL screening assays

87 unique, capped per target: 86 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3789071	Binding	Binding affinity to recombinant human MD2 (17 to 160 residues) expressed in Escherichia coli BL21(DE3) cells assessed as chi-square value by surface plasmon resonance analysis	Discovery of a New Inhibitor of Myeloid Differentiation 2 from Cinnamamide Derivatives with Anti-Inflammatory Activity in Sepsis and Acute Lung Injury. — J Med Chem
CHEMBL3373551	ADMET	Activation of TLR4/MD2 (unknown origin) expressed in HEK293 cells co-expressing CD14 assessed as induction of MyD88-dependent NF-kappaB activity after 24 hrs by NF-kappaB SEAP reporter gene assay	Characterization of TRIF selectivity in the AGP class of lipid A mimetics: role of secondary lipid chains. — Bioorg Med Chem Lett

Cellosaurus cell lines

11 cell lines: 6 transformed cell line, 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7AD	Leeporter HeLa TLR4/IL-8 luciferase	Cancer cell line	Female
CVCL_E2QR	THP-1 TLR4-CD14 NFkappaB-eGFP	Cancer cell line	Male
CVCL_E6V0	Genomeditech HEK-293 H_TLR4 Reporter	Transformed cell line	Female
CVCL_E8FE	THP1-Dual MD2-CD14-TLR4	Cancer cell line	Male
CVCL_E8FF	THP1-Dual MD2-CD14 KO-TLR4	Cancer cell line	Male
CVCL_IM82	HEK-Blue hTLR4	Transformed cell line	Female
CVCL_IM95	HEK-Blue hMD2-CD14	Transformed cell line	Female
CVCL_VI45	HEK-TLR4-YFP/MD-2	Transformed cell line	Female
CVCL_X584	THP1-XBlue-MD2-CD14	Cancer cell line	Male
CVCL_Y384	293/hMD2-CD14	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03677557	PHASE4	UNKNOWN	Safety, Tolerability, Patient Satisfaction and Cost of 16.5% Subcutaneous Immunoglobulin (Cutaquig®) Treatment
NCT00001646	PHASE3	COMPLETED	Voriconazole vs. Amphotericin B in the Treatment of Invasive Aspergillosis
NCT00220766	PHASE3	COMPLETED	Rapid Infusion of Immune Globulin Intravenous (Human) In Primary Immunodeficiency Patients
NCT00468273	PHASE3	COMPLETED	A Clinical Study of Intravenous Immunoglobulin
NCT00811174	PHASE3	TERMINATED	Efficacy, Safety and Kinetics Study of Octagam 10% in Primary Immunodeficiency Diseases
NCT01012323	PHASE3	COMPLETED	A Study of NewGam, Human Immunoglobulin 10%, in Patients With Primary Immunodeficiency Diseases
NCT01313507	PHASE3	COMPLETED	High Infusion Rate Study of Immunoglobulin Intravenous (Human) 10% (NewGam)
NCT01406470	PHASE3	COMPLETED	Phase 3 Study of Immune Globulin Intravenous (Human)IVIG-SN™ in Subjects With Primary Immunodeficiency
NCT02783482	PHASE3	COMPLETED	Study of Immune Globulin Intravenous (Human) GC5107 in Subjects With Primary Humoral Immunodeficiency
NCT02810444	PHASE3	COMPLETED	Study to Investigate Efficacy, Safety and Pharmacokinetics of BT595 in Subjects With PID
NCT03961009	PHASE3	COMPLETED	Clinical Assessment of Pharmacokinetics, Efficacy, and Safety of 10% IVIg in PID Patients
NCT04842643	PHASE3	COMPLETED	An Extension Study of TAK-664 for Japanese People With Primary Immunodeficiency Disease
NCT04944979	PHASE3	ACTIVE_NOT_RECRUITING	Clinical Assessment of Pharmacokinetics, Efficacy, and Safety of 10% IVIg in Pediatric PID Patients (KIDCARES10)
NCT06089122	PHASE3	UNKNOWN	Efficacy, Safety, and Pharmacokinetics of Shu Yang IVIG
NCT06150833	PHASE3	UNKNOWN	Efficacy and Safety and Pharmacokinetics of Boya IVIG
NCT07346859	PHASE3	RECRUITING	Study of BP-SCIG 20% in Patients With Primary Immunodeficiency (PID)
NCT00001438	PHASE2	COMPLETED	A Pilot Study of the Combination of Retinoic Acid and Interferon-Alpha2a for the Treatment of Lymphoproliferative Disorders in Children With Immunodeficiency Syndromes
NCT00176865	PHASE2	COMPLETED	Stem Cell Transplant for Immunologic or Histiocytic Disorders
NCT00389324	PHASE2	COMPLETED	A Trial of the Pharmacokinetics, Safety, and Tolerability of Subcutaneous Gamunex® in Primary Immunodeficiency
NCT00598481	PHASE2	COMPLETED	ADA Gene Transfer Into Hematopoietic Stem/Progenitor Cells for the Treatment of ADA-SCID
NCT01856582	PHASE2	TERMINATED	CD34+ Stem Cell Infusion to Augment Graft Function
NCT06199427	PHASE2	RECRUITING	PTCy and and Ruxolitinib for GVHD Prophylaxis After HSCT With Thymoglobulin in Conditioning Regimen in Patients With Inborn Errors of Immunity
NCT00001158	Not specified	COMPLETED	Studies of the Immune Response in Normal Subjects and Patients With Disorders of the Immune System
NCT00001336	Not specified	COMPLETED	In Vitro Studies of Immunological and Stem Cell Function in Peripheral Blood Mononuclear Cells in Patients
NCT00001788	Not specified	TERMINATED	Genetic Basis of Primary Immunodeficiencies
NCT00006054	Not specified	TERMINATED	Allogeneic Bone Marrow Transplantation in Patients With Primary Immunodeficiencies
NCT00006131	Not specified	COMPLETED	Randomized Study of Two Doses of Oral Valacyclovir in Immunocompromised Patients With Uncomplicated Herpes Zoster
NCT01150240	Not specified	UNKNOWN	Clinical and Laboratory Online Patient- and Research Database for Primary Immunodeficiencies in Switzerland
NCT01727895	Not specified	COMPLETED	Effects of Orally Administered Beta-glucan on Leukocyte Function in Humans
NCT02176239	Not specified	COMPLETED	Monitoring of 5% Treatment Naïve Intravenous Immunoglobulin (IVIg) Primary Immunodeficiency Disease (PIDD) Patients Using the CareExchange® System: A Pilot Study Using 5% Gammaplex® IVIg in the Home Setting
NCT02417740	Not specified	RECRUITING	Natural History of Noncirrhotic Portal Hypertension
NCT02554630	Not specified	COMPLETED	Novel Mechanisms and Approaches to Treat Neonatal Sepsis
NCT02630082	Not specified	COMPLETED	Feasibility of Measuring Immune Resp, Activation in Foreskin/Mucosa in HIV-, Uncircumcised High-HIV-risk MSM, Lima Peru
NCT02735824	Not specified	RECRUITING	Genetic Study of Immunodeficiency: Search for New Genetic Causes for Primary Immunodeficiencies
NCT03252548	Not specified	UNKNOWN	Pediatric Primary Immunodeficiency Disease (PID) in China
NCT03478670	Not specified	ENROLLING_BY_INVITATION	Strimvelis Registry Study to Follow-up Patients With Adenosine Deaminase Severe Combined Immunodeficiency (ADA-SCID)
NCT03835312	Not specified	RECRUITING	Sequential Transplantation of UCBSCs and Islet Cells in Children and Adolescents With Monogenic Immunodeficiency T1DM
NCT03920735	Not specified	UNKNOWN	Retrospective Non-interventional Analysis of Opportunistic Infections in Immunocompromised and Frail Patients
NCT04798677	Not specified	COMPLETED	Efficacy and Tolerability of ABBC1 in Volunteers Receiving the Influenza or Covid-19 Vaccine
NCT05236764	Not specified	ACTIVE_NOT_RECRUITING	Haploidentical Hematopoietic Cell Transplantation Using TCR Alpha/Beta and CD19 Depletion