CD1D

Summary

CD1D (CD1d molecule, HGNC:1637) is a protein-coding gene on chromosome 1q23.1, encoding Antigen-presenting glycoprotein CD1d (P15813). Antigen-presenting protein that binds self and non-self glycolipids and presents them to T-cell receptors on natural killer T-cells.

This gene encodes a divergent member of the CD1 family of transmembrane glycoproteins, which are structurally related to the major histocompatibility complex (MHC) proteins and form heterodimers with beta-2-microglobulin. The CD1 proteins mediate the presentation of primarily lipid and glycolipid antigens of self or microbial origin to T cells. The human genome contains five CD1 family genes organized in a cluster on chromosome 1. The CD1 family members are thought to differ in their cellular localization and specificity for particular lipid ligands. The protein encoded by this gene localizes to late endosomes and lysosomes via a tyrosine-based motif in the cytoplasmic tail. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 912 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 62 total
• Druggable target: yes
• MANE Select transcript: NM_001371762

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1637
Approved symbol	CD1D
Name	CD1d molecule
Location	1q23.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000158473
Ensembl biotype	protein_coding
OMIM	188410
Entrez	912

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 11 protein_coding, 2 retained_intron

ENST00000368171, ENST00000673623, ENST00000673701, ENST00000673723, ENST00000674023, ENST00000674047, ENST00000674085, ENST00000866546, ENST00000866547, ENST00000866548, ENST00000925508, ENST00000953811, ENST00000953812

RefSeq mRNA: 5 — MANE Select: NM_001371762 NM_001319145, NM_001371761, NM_001371762, NM_001371763, NM_001766

CCDS: CCDS1173, CCDS91074, CCDS91075

Canonical transcript exons

ENST00000674085 — 6 exons

Exon	Start	End
ENSE00001039117	158182032	158182310
ENSE00001039119	158181455	158181721
ENSE00001308386	158183936	158184035
ENSE00002360170	158182878	158183156
ENSE00003897946	158180895	158181162
ENSE00003899570	158184129	158186427

Expression profiles

Bgee: expression breadth ubiquitous, 172 present calls, max score 96.23.

FANTOM5 (CAGE): breadth broad, TPM avg 1.9601 / max 114.6114, expressed in 334 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5818	1.6570	299
5819	0.3031	138

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	96.23	gold quality
mononuclear cell	CL:0000842	96.05	gold quality
leukocyte	CL:0000738	95.77	gold quality
granulocyte	CL:0000094	94.70	gold quality
thymus	UBERON:0002370	88.21	gold quality
spleen	UBERON:0002106	87.65	gold quality
blood	UBERON:0000178	86.73	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.62	gold quality
small intestine Peyer’s patch	UBERON:0003454	84.61	gold quality
right lobe of liver	UBERON:0001114	84.39	gold quality
small intestine	UBERON:0002108	82.19	gold quality
vermiform appendix	UBERON:0001154	81.70	gold quality
jejunal mucosa	UBERON:0000399	80.70	gold quality
duodenum	UBERON:0002114	79.40	gold quality
ileal mucosa	UBERON:0000331	78.70	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.73	gold quality
rectum	UBERON:0001052	77.25	gold quality
liver	UBERON:0002107	76.95	gold quality
bone marrow	UBERON:0002371	76.59	gold quality
bone marrow cell	CL:0002092	76.41	gold quality
lymph node	UBERON:0000029	75.41	gold quality
caecum	UBERON:0001153	75.37	gold quality
right lung	UBERON:0002167	75.32	gold quality
mucosa of transverse colon	UBERON:0004991	74.81	gold quality
trabecular bone tissue	UBERON:0002483	74.44	gold quality
transverse colon	UBERON:0001157	74.41	gold quality
apex of heart	UBERON:0002098	73.64	gold quality
intestine	UBERON:0000160	73.12	gold quality
frontal pole	UBERON:0002795	72.33	gold quality
gall bladder	UBERON:0002110	71.96	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	21.91
E-CURD-112	yes	13.82
E-MTAB-6678	yes	8.16
E-MTAB-9801	yes	6.38
E-ANND-3	yes	5.52

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, ELF1, HDAC1, HDAC2, LEF1, MYB, PPARG, RARA, SP1, SPI1, TCF7

miRNA regulators (miRDB)

75 targeting CD1D, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-142-3P	99.62	71.30	974

Literature-anchored findings (GeneRIF, showing 40)

• Data show that CD1d associates in the ER with both calnexin and calreticulin and with the thiol oxidoreductase ERp57 in a manner dependent on glucose trimming of its N-linked glycans. (PMID:12239218)
• CD1d ligand at the human maternal-fetal interface (PMID:12368486)
• B cell chronic lymphocytic leukemia cells significantly down-regulated transcripts from CD1c and CD1d genes, permitting cells to evade the immune response (PMID:12454749)
• the CD1d alpha1-alpha2 domains of both rhesus monkeys and humans are highly homologous (95.6%) (PMID:12618910)
• CD1d is expressed functionally on IECs with a polarity of presentation (basal > apical) predicting a role in presentation of mucosal glycolipid antigens to local CD1d-restricted T cells. (PMID:12730881)
• a novel autocrine pathway of CD1d regulation by Hsp110. (PMID:12952923)
• CD1d proteins sre strong binders of small hydrophobic probes such as 1-anilinonaphthalene-8-sulfonic acid and 4,4’-dianilino-1,1’-naphthyl-5,5’-disulfonic acid. (PMID:14551186)
• saposins mobilize monomeric lipids from lysosomal membranes and facilitate their association with CD1d (PMID:14716312)
• Investigation of the 5’ upstream region of human CD1D reveals multiple transcription initiation sites and TATA boxless dual promoters located within 700 base pairs 5’ upstream of the coding region. (PMID:15100293)
• Transgenic overexpression of CD1d within pancreatic islets of nonobese diabetic (NOD) mice protects them from autoimmune diabetes through activation of NKT cells and improvement of IL-4 secretion at the site of autoimmunity (i.e., peripheral lymph nodes). (PMID:15128771)
• CD1d can inhibit NK cell-mediated cytolysis; the putative inhibitory receptor does not recognize CD1d molecules loaded with alpha-GalCer (PMID:15187105)
• Data show that phosphatidylinositol mannoside represents a mycobacterial antigen recognized by T cells in the context of CD1d. (PMID:15243159)
• Hepatic inflammatory cells & biliary cells near portal tract fibrotic areas of HCV-infected donors specifically up-regulate CD1d. CD1d presentation of liver Ag may be beneficial in acute viral clearance, but in chronic infection could add to liver injury. (PMID:15265953)
• The ability of CD1d-unrestricted natural killer T cells to recruit innate immune system cells might play a role in cancer cell eradication and contribute to inflammatory diseases. (PMID:15345586)
• TGFbeta produced by keratinocytes contribute to selectively downregulate CD1d expression on intraepidermal-resident Langerhans cells (PMID:15654963)
• CD1d-dimer staining revealed human natural killer T cells reactivity toward Sphingomonas glycosphingolipids. (PMID:15665086)
• ability of Nef to alter the cell surface expression of human CD1d. In cells co-expressing CD1d and Nef, a reduction in the cell surface level of CD1d was observed. (PMID:15916790)
• analysis of the crystal structure of human CD1d in complex with synthetic alpha-galactosylceramide at a resolution of 3.0 A (PMID:16007090)
• CD1d ligation alone, in the absence of iNKT, could rapidly (within 24 h) stimulate production of bioactive IL-12p70 by CD1d+ human peripheral blood monocytes as well as immature dendritic cells (PMID:16091469)
• CD1d continues to play a role in late-stage NKT cell development and, in particular, during the functionally significant acquisition of NK1.1 that is indicative of NKT cell maturity (PMID:16148122)
• CD1d has a role in intrahepatic T-cell recognition in hepatocytes (PMID:16178273)
• Time-course studies of CD1d gene expression indicated that keratinocytes slowly increased gene expression with CaCl(2)-induced terminal differentiation (PMID:16456021)
• These results highlight the variation in Ag recognition among CD1d-restricted Receptors, Antigen, T-Cell (TCRs) and suggest that TCR alpha-chain elements contribute to alpha-linked glycosphingolipid specificity [CD1d] (PMID:16517731)
• CD1d-restricted gamma delta T cells specific for phospholipids can represent a key mucosal regulatory subset for the control of early host reactivity against tree pollens. (PMID:16675349)
• This review highlights the role of the CD1d antigen processing pathway and the immunopotentiating effects of the ligands that can be presented by CD1d to natural killer (NK)T cells or other CD1d-restricted T cells during cancer and infections. (PMID:16818729)
• Schwann cells activated iNKT cells in a CD1d-dependent manner in the presence of alpha-galactosylceramide (PMID:17015708)
• CD1d has a role in cytolysis of lymphoblastic lymphoma cells (PMID:17071498)
• One of the N-linked glycans (at position asparagine-42) exists mainly in a form that is sensitive to endoglycosidase H. Deletion of Asn-42 affects stability of the CD1d heavy chain beta 2-microglobulin heterodimer. (PMID:17071611)
• CD4 potentiates human iNKT cell activation by engaging CD1d molecules. These results indicate that the CD4 coreceptors may contribute to the fine tuning of iNKT cells reactivity. (PMID:17363727)
• saposin B may facilitate lipid binding to CD1d molecules throughout the endocytic pathway (PMID:17372201)
• Cotrafficking with major histocompatibility class II molecules and the invariant chain (Ii) selectively enhances CD1d-mediated presentation of exogenous antigens. (PMID:17475845)
• CD1d-restricted NKT cells have roles in the intestine and in inflammatory bowel diseases [review] (PMID:17476670)
• The structure provides a basis for the interaction between the highly conserved NKT TCR alpha-chain and the CD1d-antigen complex (PMID:17581592)
• These results indicate that CD4 can contribute to natural killer cell activation independently of the presence of a CD4-ligand on antigen presenting cells and suggest that it preferentially modulates cytokine and proliferative responses. (PMID:17726154)
• Used a lentiviral system to generate stable cell lines producing beta2m-CD1d single chain protein which was used to form CD1d tetramer. (PMID:18068183)
• Data indicate that viral danger signals trigger NKT cell activation by enhancing CD1d de novo synthesis through increasing the abundance of CD1D mRNA in human myeloid dendritic cells. (PMID:18253929)
• monocyte-derived DCs cultured in an immunoglobulin-rich milieu expressed CD1d but not CD1a, CD1b, and CD1c, whereas DCs cultured in the presence of low levels of immunoglobulins had an opposite CD1 profile (PMID:18337560)
• An alanine scanning mutagenesis approach was undertook to define the energetic basis of this interaction between the natural killer cell T cell receptors and CD1d. (PMID:18378792)
• PKCzeta is an important transduction molecule downstream of TNF-alpha signaling and is associated with increased expression of CD1d that may enhance CD1d-natural killer T cell interactions in psoriasis lesions. (PMID:18385757)
• Trophoblast differentiation is characterized by TGF-beta1-mediated decreases in trophoblast cell CD1d expression. (PMID:18433720)

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
danio_rerio	mhc1laa	ENSDARG00000016056
danio_rerio	mhc1lba	ENSDARG00000016227
danio_rerio	mhc1lda	ENSDARG00000023203
danio_rerio		ENSDARG00000051710
danio_rerio		ENSDARG00000051711
danio_rerio	mhc1lfa	ENSDARG00000051712
danio_rerio	mhc1lga	ENSDARG00000051713
danio_rerio	mhc1lca	ENSDARG00000055813
danio_rerio	mhc1lja	ENSDARG00000096830
danio_rerio	si:dkey-52p2.5	ENSDARG00000096940
danio_rerio	mhc1lla	ENSDARG00000096977
mus_musculus	Cd1d1	ENSMUSG00000028076
mus_musculus	Cd1d2	ENSMUSG00000041750
rattus_norvegicus	Cd1d1	ENSRNOG00000016451

Paralogs (22): HFE (ENSG00000010704), FCGRT (ENSG00000104870), ULBP1 (ENSG00000111981), ULBP2 (ENSG00000131015), ULBP3 (ENSG00000131019), MR1 (ENSG00000153029), RAET1L (ENSG00000155918), CD1A (ENSG00000158477), CD1C (ENSG00000158481), CD1B (ENSG00000158485), CD1E (ENSG00000158488), AZGP1 (ENSG00000160862), RAET1E (ENSG00000164520), RAET1G (ENSG00000203722), MICB (ENSG00000204516), MICA (ENSG00000204520), HLA-C (ENSG00000204525), HLA-E (ENSG00000204592), HLA-G (ENSG00000204632), HLA-F (ENSG00000204642), HLA-A (ENSG00000206503), HLA-B (ENSG00000234745)

Protein

Protein identifiers

Antigen-presenting glycoprotein CD1d — P15813 (reviewed: P15813)

Alternative names: R3G1

All UniProt accessions (3): P15813, A0A669KAZ2, A0A669KB34

UniProt curated annotations — full annotation on UniProt →

Function. Antigen-presenting protein that binds self and non-self glycolipids and presents them to T-cell receptors on natural killer T-cells.

Subunit / interactions. Heterodimer with B2M (beta-2-microglobulin). Interacts with MHC II.

Subcellular location. Cell membrane. Basolateral cell membrane. Endosome membrane. Lysosome membrane. Endoplasmic reticulum membrane.

Tissue specificity. Expressed on cortical thymocytes, on certain T-cell leukemias, and in various other tissues.

Miscellaneous. During protein synthesis and maturation, CD1 family members bind endogenous lipids that are replaced by lipid or glycolipid antigens when the proteins are internalized and pass through endosomes, before trafficking back to the cell surface.

RefSeq proteins (5): NP_001306074, NP_001358690, NP_001358691, NP_001358692, NP_001757 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003597	Ig_C1-set	Domain
IPR007110	Ig-like_dom	Domain
IPR011161	MHC_I-like_Ag-recog	Domain
IPR011162	MHC_I/II-like_Ag-recog	Homologous_superfamily
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR037055	MHC_I-like_Ag-recog_sf	Homologous_superfamily
IPR050208	MHC_class-I_related	Family

Pfam: PF07654, PF16497

UniProt features (47 total): strand 18, helix 7, glycosylation site 4, turn 4, disulfide bond 2, mutagenesis site 2, topological domain 2, binding site 2, signal peptide 1, chain 1, sequence variant 1, transmembrane region 1, domain 1, short sequence motif 1

Structure

Experimental structures (PDB)

22 structures.

PDB	Method	Resolution (Å)
8SOS	X-RAY DIFFRACTION	2.33
6V7Y	X-RAY DIFFRACTION	2.4
4WW2	X-RAY DIFFRACTION	2.48
3HUJ	X-RAY DIFFRACTION	2.5
4WO4	X-RAY DIFFRACTION	2.5
8SGM	X-RAY DIFFRACTION	2.5
4EN3	X-RAY DIFFRACTION	2.57
4MQ7	X-RAY DIFFRACTION	2.6
6V7Z	X-RAY DIFFRACTION	2.75
3U0P	X-RAY DIFFRACTION	2.8
8SGB	X-RAY DIFFRACTION	2.8
9O4X	X-RAY DIFFRACTION	2.86
4LHU	X-RAY DIFFRACTION	2.87
3VWK	X-RAY DIFFRACTION	2.94
1ZT4	X-RAY DIFFRACTION	3
4MNG	X-RAY DIFFRACTION	3.01
3TZV	X-RAY DIFFRACTION	3.06
3VWJ	X-RAY DIFFRACTION	3.09
4WWK	X-RAY DIFFRACTION	3.1
3SDX	X-RAY DIFFRACTION	3.12
2PO6	X-RAY DIFFRACTION	3.2
6V80	X-RAY DIFFRACTION	3.53

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P15813-F1	90.20	0.83

Antibody-complex structures (SAbDab): 4 — 6V7Y, 6V7Z, 6V80, 8SOS

Functional residue map

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

Ligand- & substrate-binding residues (2): 98; 169–172

Disulfide bonds (2): 120–184, 224–279

Glycosylation sites (4): 60, 126, 181, 38

Mutagenesis-validated functional residues (2):

Position	Phenotype
331	strongly reduced internalization.
334	strongly reduced internalization.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-198933	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-1280218	Adaptive Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 349 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, MCLACHLAN_DENTAL_CARIES_UP, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, MODULE_255, GOCC_VACUOLAR_MEMBRANE, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, MODULE_317, GOCC_CELL_SURFACE, GOBP_LEUKOCYTE_MEDIATED_CYTOTOXICITY, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_VIA_MHC_CLASS_IB, GOBP_DETECTION_OF_OTHER_ORGANISM, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION

GO Biological Process (11): positive regulation of T cell mediated cytotoxicity (GO:0001916), immune response (GO:0006955), detection of bacterium (GO:0016045), heterotypic cell-cell adhesion (GO:0034113), positive regulation of T cell proliferation (GO:0042102), T cell selection (GO:0045058), innate immune response (GO:0045087), positive regulation of innate immune response (GO:0045089), antigen processing and presentation, endogenous lipid antigen via MHC class Ib (GO:0048006), antigen processing and presentation, exogenous lipid antigen via MHC class Ib (GO:0048007), immune system process (GO:0002376)

GO Molecular Function (7): beta-2-microglobulin binding (GO:0030881), lipid antigen binding (GO:0030882), endogenous lipid antigen binding (GO:0030883), exogenous lipid antigen binding (GO:0030884), cell adhesion molecule binding (GO:0050839), lipopeptide binding (GO:0071723), protein binding (GO:0005515)

GO Cellular Component (13): obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), lysosome (GO:0005764), lysosomal membrane (GO:0005765), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), endosome membrane (GO:0010008), basolateral plasma membrane (GO:0016323), endosome (GO:0005768), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Adaptive Immune System	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
immune system process	2
antigen processing and presentation of lipid antigen via MHC class Ib	2
protein binding	2
lipid binding	2
lipid antigen binding	2
endomembrane system	2
positive regulation of leukocyte mediated cytotoxicity	1
T cell mediated cytotoxicity	1
regulation of T cell mediated cytotoxicity	1
positive regulation of T cell mediated immunity	1
response to stimulus	1
response to bacterium	1
detection of other organism	1
cell-cell adhesion	1
T cell proliferation	1
regulation of T cell proliferation	1
positive regulation of lymphocyte proliferation	1
positive regulation of T cell activation	1
T cell differentiation	1
immune response	1
defense response to symbiont	1
positive regulation of response to biotic stimulus	1
positive regulation of defense response	1
positive regulation of response to external stimulus	1
innate immune response	1
regulation of innate immune response	1
positive regulation of immune response	1
antigen processing and presentation of endogenous antigen	1
antigen processing and presentation of exogenous antigen	1
biological_process	1
antigen binding	1
binding	1
intracellular anatomical structure	1
lytic vacuole	1
lysosome	1
lytic vacuole membrane	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle membrane	1

Protein interactions and networks

STRING

2174 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD1D	B2M	P01884	973
CD1D	CD83	Q01151	914
CD1D	CD207	Q9UJ71	907
CD1D	CD4	P01730	906
CD1D	CD8A	P01732	887
CD1D	IFNG	P01579	875
CD1D	CD40LG	P29965	872
CD1D	CD68	P34810	871
CD1D	IL4	P05112	868
CD1D	KLRB1	Q12918	846
CD1D	IL10	P22301	840
CD1D	CD40	P25942	837
CD1D	CD5	P06127	826
CD1D	CD86	P42081	804
CD1D	CD80	P33681	791

IntAct

10 interactions, top by confidence:

A	B	Type	Score
CD1D	B2M	psi-mi:“MI:0407”(direct interaction)	0.440
DLG1	CD1D	psi-mi:“MI:0407”(direct interaction)	0.440
CD1D	CEACAM5	psi-mi:“MI:0407”(direct interaction)	0.440
LILRB2	CD1D	psi-mi:“MI:0407”(direct interaction)	0.440
CD1D	MINDY1	psi-mi:“MI:0915”(physical association)	0.400
CD1D	PTEN	psi-mi:“MI:2364”(proximity)	0.270
PTPN11	CD1D	psi-mi:“MI:2364”(proximity)	0.270
BRAF	CD1D	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (6): CANX (Affinity Capture-Western), CALR (Affinity Capture-Western), B2M (Affinity Capture-Western), P4HTM (Affinity Capture-Western), FAM63A (Affinity Capture-MS), PTPRC (Affinity Capture-Western)

ESM2 similar proteins: O35799, O62848, P01898, P01899, P06126, P06339, P10321, P11609, P11610, P13747, P13752, P13753, P14429, P14430, P15812, P15813, P15978, P16212, P16215, P17693, P23043, P29016, P29017, P30511, P30515, P30516, P30517, P60018, P70387, Q28565, Q29422, Q30201, Q3ZCH5, Q4ACW4, Q5YB65, Q63493, Q95IT1, Q95IT3, Q9GKZ0, Q9GL41

Diamond homologs: O62848, P04440, P06126, P11609, P11610, P13762, P15812, P15813, P18470, P20756, P23042, P23043, P23068, P29016, P29017, P79483, P80943, Q07717, Q28565, Q29422, Q30154, Q4ACW4, Q5YB65, Q63493, Q8AYH8, Q9QZY5, Q9QZY6, Q9QZY7, Q9QZY8, Q9QZY9, Q9QZZ0, Q9QZZ1, Q9QZZ2, Q9XS72, C1ITJ8, O19477, O35799, O73895, P01870, P01889

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	53
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1200 predictions. Top by Δscore:

Variant	Effect	Δscore
1:158180964:G:GT	donor_gain	1.0000
1:158181685:G:GT	donor_gain	1.0000
1:158181685:G:T	donor_gain	1.0000
1:158181694:G:GT	donor_gain	1.0000
1:158181709:C:G	donor_gain	1.0000
1:158181727:C:G	donor_gain	1.0000
1:158180908:C:G	donor_gain	0.9900
1:158181399:T:G	acceptor_gain	0.9900
1:158181399:T:TA	acceptor_gain	0.9900
1:158181683:GGGAC:G	donor_gain	0.9900
1:158181684:GGACG:G	donor_gain	0.9900
1:158181695:A:T	donor_gain	0.9900
1:158181722:G:GG	donor_gain	0.9900
1:158181732:GGA:G	donor_gain	0.9900
1:158181760:G:T	donor_gain	0.9900
1:158182140:G:GT	donor_gain	0.9900
1:158182288:G:T	donor_gain	0.9900
1:158184127:A:AG	acceptor_gain	0.9900
1:158184128:G:GA	acceptor_gain	0.9900
1:158180965:A:T	donor_gain	0.9800
1:158181015:G:T	donor_gain	0.9800
1:158181398:AT:A	acceptor_gain	0.9800
1:158181398:ATGCT:A	acceptor_gain	0.9800
1:158181402:T:A	acceptor_gain	0.9800
1:158181453:A:AG	acceptor_gain	0.9800
1:158181454:G:GG	acceptor_gain	0.9800
1:158184036:G:GG	donor_gain	0.9800
1:158184124:CACA:C	acceptor_loss	0.9800
1:158184127:AG:A	acceptor_loss	0.9800
1:158181708:GC:G	donor_gain	0.9700

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000391164 (1:158180483 G>C), RS1000407328 (1:158180298 G>T), RS1000581465 (1:158184298 C>A), RS1000655043 (1:158184651 C>G), RS1001587959 (1:158185845 A>G), RS1001661391 (1:158186067 C>G,T), RS1001672659 (1:158183874 G>A,T), RS1001696334 (1:158179618 G>A,T), RS1002076379 (1:158178623 C>T), RS1002420191 (1:158185796 T>C), RS1002753053 (1:158181079 G>C), RS1003096060 (1:158182663 A>T), RS1003525102 (1:158177784 C>A,G), RS1003725661 (1:158182201 C>T), RS1004151400 (1:158177658 A>C,T)

Disease associations

OMIM: gene MIM:188410 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009269_21	Dental caries (decayed and filled deciduous teeth)	3.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1649053 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: other protein — CD molecules

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tretinoin	affects cotreatment, increases expression, decreases reaction, affects binding, increases reaction	4
sodium arsenite	decreases expression, increases expression	3
Benzo(a)pyrene	decreases expression, decreases methylation, increases methylation	3
Am 580	increases expression, decreases reaction	2
Arsenic Trioxide	affects cotreatment, increases expression, decreases expression	2
Nickel	increases expression	2
Valproic Acid	increases expression	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
bisphenol A	increases methylation	1
trichostatin A	increases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	decreases expression	1
tobacco tar	decreases expression, decreases reaction	1
diallyl disulfide	decreases expression, decreases reaction	1
allyl sulfide	decreases expression, decreases reaction	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
Ro 41-5253	decreases reaction, increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
bisphenol S	decreases methylation	1
(+)-JQ1 compound	decreases expression	1
Adapalene	increases expression	1
Rosiglitazone	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, decreases expression	1
Amphotericin B	decreases expression	1
Carbamazepine	affects expression	1
Dactinomycin	decreases reaction, increases expression	1
Estradiol	decreases expression	1

ChEMBL screening assays

16 unique, capped per target: 16 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1073800	Binding	Induction of CD1D-mediated IL-13 production in human iNKT cells expressing CD4 at 400 nM after 18 hrs by ELISA	Syntheses and biological activities of KRN7000 analogues having aromatic residues in the acyl and backbone chains with varying stereochemistry. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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