CD1E

Summary

CD1E (CD1e molecule, HGNC:1638) is a protein-coding gene on chromosome 1q23.1, encoding T-cell surface glycoprotein CD1e, membrane-associated (P15812). T-cell surface glycoprotein CD1e, soluble binds diacetylated lipids, including phosphatidyl inositides and diacylated sulfoglycolipids, and is required for the presentation of glycolipid antigens on the cell surface.

This gene encodes a 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 within Golgi compartments, endosomes, and lysosomes, and is cleaved into a stable soluble form. The soluble form is required for the intracellular processing of some glycolipids into a form that can be presented by other CD1 family members. Many alternatively spliced transcript variants encoding different isoforms have been described. Additional transcript variants have been found; however, their biological validity has not been determined.

Source: NCBI Gene 913 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 70 total — 1 likely-pathogenic
• GTEx eGene: eQTL in 15 tissues, sQTL in 0 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.52 (unconstrained)
• MANE Select transcript: NM_030893
• Notable: 70 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1638
Approved symbol	CD1E
Name	CD1e molecule
Location	1q23.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000158488
Ensembl biotype	protein_coding
OMIM	188411
Entrez	913

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 19 protein_coding, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000368167

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 14, TSL 3: 1

ENST00000368167, ENST00000368154, ENST00000368155, ENST00000368156, ENST00000368157, ENST00000368160, ENST00000368161, ENST00000368162, ENST00000368163, ENST00000368164, ENST00000368165, ENST00000368166, ENST00000444681, ENST00000452291, ENST00000464822, ENST00000882312, ENST00000882313, ENST00000882314, ENST00000951300, ENST00001143150

RefSeq mRNA: 13 — MANE Select: NM_030893 NM_001042583, NM_001042584, NM_001042585, NM_001042586, NM_001042587, NM_001185107, NM_001185108, NM_001185110, NM_001185112, NM_001185113, NM_001185114, NM_001185115, NM_030893

CCDS: CCDS41417, CCDS41418, CCDS41419, CCDS41420, CCDS41421, CCDS41422, CCDS53384, CCDS53385, CCDS53386, CCDS53387, CCDS53388, CCDS53389, CCDS53390

Canonical transcript exons

ENST00000368167 — 6 exons

Exon	Start	End
ENSE00001039224	158355300	158355569
ENSE00001168041	158354377	158354673
ENSE00001446453	158353894	158354046
ENSE00002228805	158356728	158357553
ENSE00002425255	158355827	158356105
ENSE00003642396	158356498	158356591

Expression profiles

Bgee: expression breadth ubiquitous, 148 present calls, max score 97.61.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 3.1614 / max 1607.9373, expressed in 77 samples.

Highest expression (Bgee): thymus, male germ line stem cell (sensu Vertebrata) in testis, buccal mucosa cell, upper leg skin, gall bladder.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CD1E is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 15 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

15 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Not Sun Exposed Suprapubic	eqtl	4.7e-11	+0.24	1:158336919:T:C
Skin Sun Exposed Lower leg	eqtl	3.3e-09	+0.19	1:158337766:T:G
Whole Blood	eqtl	3.6e-07	-0.23	1:158449882:C:A
Nerve Tibial	eqtl	1.0e-04	+0.47	1:158361160:C:T
Pancreas	eqtl	1.4e-04	+0.61	1:158387285:C:T
Colon Sigmoid	eqtl	2.7e-04	+0.67	1:158361229:C:A
Esophagus Mucosa	eqtl	4.7e-04	+0.26	1:158359487:C:T
Artery Tibial	eqtl	7.6e-04	+0.28	1:158359487:C:T
Thyroid	eqtl	1.4e-02	+0.19	1:158371483:G:A
Stomach	eqtl	1.4e-02	+0.32	1:158377450:G:A
Adipose Subcutaneous	eqtl	1.8e-02	-0.60	1:157960511:G:C
Colon Transverse	eqtl	2.4e-02	+0.50	1:158398239:C:G
Esophagus Muscularis	eqtl	3.7e-02	+0.74	1:158286226:G:A
Lung	eqtl	4.1e-02	+0.31	1:159242576:A:G
Artery Aorta	eqtl	4.6e-02	+1.19	1:159264539:A:G

FANTOM5 promoters

showing 10 of 36 alternative TSS:

Promoter ID	TPM avg	Samples expressed
5867	2.1042	66
5876	0.1626	10
5859	0.1434	7
5866	0.1114	10
5873	0.0991	12
5879	0.0682	5
5860	0.0663	6
5877	0.0560	5
5862	0.0470	5
5875	0.0466	7

Top tissues by expression

showing 100 of 273 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
thymus	UBERON:0002370	97.61	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.46	gold quality
buccal mucosa cell	CL:0002336	86.78	gold quality
upper leg skin	UBERON:0004262	84.74	gold quality
gall bladder	UBERON:0002110	74.19	gold quality
granulocyte	CL:0000094	73.01	gold quality
skin of hip	UBERON:0001554	72.89	gold quality
leukocyte	CL:0000738	71.56	gold quality
monocyte	CL:0000576	71.44	gold quality
mononuclear cell	CL:0000842	71.24	gold quality
lymph node	UBERON:0000029	70.35	gold quality
rectum	UBERON:0001052	69.91	gold quality
palpebral conjunctiva	UBERON:0001812	69.54	gold quality
epithelial cell of pancreas	CL:0000083	68.45	gold quality
type B pancreatic cell	CL:0000169	67.73	gold quality
skin of abdomen	UBERON:0001416	67.02	gold quality
vermiform appendix	UBERON:0001154	66.87	gold quality
zone of skin	UBERON:0000014	66.08	gold quality
oral cavity	UBERON:0000167	64.98	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	64.73	gold quality
cervix squamous epithelium	UBERON:0006922	64.22	gold quality
esophagus mucosa	UBERON:0002469	64.06	gold quality
esophagus squamous epithelium	UBERON:0006920	64.02	silver quality
skin of leg	UBERON:0001511	63.85	gold quality
caecum	UBERON:0001153	62.68	gold quality
lateral nuclear group of thalamus	UBERON:0002736	62.27	gold quality
epithelium of esophagus	UBERON:0001976	62.23	silver quality
squamous epithelium	UBERON:0006914	62.07	silver quality
tongue squamous epithelium	UBERON:0006919	61.64	gold quality
smooth muscle tissue	UBERON:0001135	60.89	gold quality
upper arm skin	UBERON:0004263	60.65	gold quality
duodenum	UBERON:0002114	60.52	gold quality
gluteal muscle	UBERON:0002000	60.42	gold quality
triceps brachii	UBERON:0001509	59.54	gold quality
lower esophagus mucosa	UBERON:0035834	59.22	gold quality
pancreatic ductal cell	CL:0002079	58.82	silver quality
periodontal ligament	UBERON:0008266	58.55	gold quality
endometrium epithelium	UBERON:0004811	58.20	gold quality
vena cava	UBERON:0004087	58.12	gold quality
mammalian vulva	UBERON:0000997	57.91	gold quality
diaphragm	UBERON:0001103	56.70	gold quality
myocardium	UBERON:0002349	56.66	gold quality
mucosa of transverse colon	UBERON:0004991	56.37	gold quality
colonic mucosa	UBERON:0000317	56.04	silver quality
endothelial cell	CL:0000115	55.83	gold quality
calcaneal tendon	UBERON:0003701	55.51	gold quality
urinary bladder	UBERON:0001255	54.90	gold quality
mucosa of sigmoid colon	UBERON:0004993	54.80	gold quality
tendon of biceps brachii	UBERON:0008188	54.51	gold quality
jejunal mucosa	UBERON:0000399	54.43	gold quality
vagina	UBERON:0000996	54.34	gold quality
ileal mucosa	UBERON:0000331	54.26	silver quality
fallopian tube	UBERON:0003889	54.14	gold quality
spleen	UBERON:0002106	53.96	gold quality
tonsil	UBERON:0002372	53.96	gold quality
esophagus	UBERON:0001043	53.78	gold quality
blood	UBERON:0000178	53.72	gold quality
quadriceps femoris	UBERON:0001377	53.70	gold quality
middle temporal gyrus	UBERON:0002771	53.67	gold quality
endometrium	UBERON:0001295	53.25	gold quality
parotid gland	UBERON:0001831	53.25	gold quality
metanephric glomerulus	UBERON:0004736	53.24	gold quality
upper lobe of left lung	UBERON:0008952	53.21	gold quality
vastus lateralis	UBERON:0001379	53.18	gold quality
right coronary artery	UBERON:0001625	53.15	gold quality
lung	UBERON:0002048	53.14	gold quality
small intestine	UBERON:0002108	53.11	gold quality
deltoid	UBERON:0001476	53.02	gold quality
saliva-secreting gland	UBERON:0001044	53.00	gold quality
upper lobe of lung	UBERON:0008948	52.93	gold quality
superficial temporal artery	UBERON:0001614	52.82	gold quality
Brodmann (1909) area 46	UBERON:0006483	52.75	gold quality
tendon	UBERON:0000043	52.74	gold quality
nasal cavity epithelium	UBERON:0005384	52.61	gold quality
uterine cervix	UBERON:0000002	52.57	gold quality
pericardium	UBERON:0002407	52.44	gold quality
small intestine Peyer’s patch	UBERON:0003454	52.43	gold quality
renal glomerulus	UBERON:0000074	52.30	gold quality
nephron tubule	UBERON:0001231	52.20	gold quality
mouth mucosa	UBERON:0003729	52.14	gold quality
body of tongue	UBERON:0011876	52.08	gold quality
minor salivary gland	UBERON:0001830	51.96	gold quality
pons	UBERON:0000988	51.74	gold quality
heart right ventricle	UBERON:0002080	51.71	gold quality
kidney epithelium	UBERON:0004819	51.65	gold quality
intestine	UBERON:0000160	51.54	gold quality
large intestine	UBERON:0000059	51.25	gold quality
Brodmann (1909) area 10	UBERON:0013541	51.08	gold quality
gingival epithelium	UBERON:0001949	51.06	gold quality
trabecular bone tissue	UBERON:0002483	50.91	gold quality
colon	UBERON:0001155	50.76	gold quality
hair follicle	UBERON:0002073	50.44	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
Brodmann (1909) area 23	UBERON:0013554	50.41	gold quality
biceps brachii	UBERON:0001507	50.39	gold quality
muscle tissue	UBERON:0002385	50.31	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
fundus of stomach	UBERON:0001160	49.94	gold quality
right uterine tube	UBERON:0001302	49.87	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-79	yes	3584.69
E-MTAB-6505	yes	1989.26
E-ANND-5	yes	662.79
E-MTAB-8410	yes	13.34
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enriched

50 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Thymus	tissue	895.4
Skin 1	tissue	13.1	not detected
Tonsil	tissue	9.2	medium
Esophagus	tissue	7.4	not detected
Lymph node	tissue	6.0	medium
Rectum	tissue	5.3	low
Spleen	tissue	4.8	low
Stomach 1	tissue	4.5	low
Gallbladder	tissue	4.5	low
Appendix	tissue	4.2	low
Lung	tissue	2.9	low
Urinary bladder	tissue	2.6	not detected
Small intestine	tissue	2.6	low
Duodenum	tissue	2.1	low
Cervix	tissue	2.0	not detected
Colon	tissue	1.9	low
Breast	tissue	1.7	not detected
Salivary gland	tissue	1.4	low
Liver	tissue	1.4	low
Endometrium 1	tissue	1.0	low
Prostate	tissue	1.0	not detected
Heart muscle	tissue	0.9	low
Fallopian tube	tissue	0.9	low
Vagina	tissue	0.8	not detected
Smooth muscle	tissue	0.8	not detected
Kidney	tissue	0.8	low
Adipose tissue	tissue	0.7	not detected
Thyroid gland	tissue	0.7	low
Seminal vesicle	tissue	0.6	low
Testis	tissue	0.5	medium
Parathyroid gland	tissue	0.5	not detected
Skeletal muscle	tissue	0.4	low
Epididymis	tissue	0.4	medium
Adrenal gland	tissue	0.4	low
Ovary	tissue	0.3	low
Pancreas	tissue	0.3	not detected
Tongue	tissue	0.2
Pituitary gland	tissue	0.1
Prefrontal cortex	tissue	0.1
Cerebral cortex	tissue	0.1	low
Motor cortex	tissue	0.1
Cingulate cortex	tissue	0.1
Somatosensory cortex	tissue	0.1
Retrosplenial cortex	tissue	0.1
Occipital cortex	tissue	0.1
Insular cortex	tissue	0.1
Basal ganglia	tissue	0.0	low
Placenta	tissue	0.0	low
Bone marrow	tissue	0.0	low
Nasopharynx	tissue	-1.0	low

Brain sub-regions (HPA Brain Atlas): detected in 7; highest nTPM — Blood vessel (0.3), Anterior funiculus (white matter) (0.1), Anterior thalamic nucleus, ventral (0.1), Lateral hypothalamic area (0.1), Nucleus ambiguus (0.1).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CD1E by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 56 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-548G-3P	99.48	68.67	2159
HSA-MIR-6165	99.44	67.12	1389
HSA-MIR-1276	99.36	68.18	1642

Functional genomics

gnomAD constraint: pLI 1.39e-21, LOEUF 1.52, missense Z 0.0242 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000368167 — one region, missense o/e 1.04.

Literature-anchored findings (GeneRIF, showing 20)

• substitutions lead to amino acid changes at position 73 and 77 of the alpha1 domain in the former and at position 30 of the alpha2 domain in the latter suggesting that the CD1E gene is much more polymorphic than previously assumed. (PMID:12144626)
• cellular and biochemical properties of the human and simian CD1e molecules are similar, suggesting that the particular intracellular distribution of CD1e is important for its physiological and/or immunological function (PMID:12671734)
• required for processing of the mycobcterial antigens hexamannosylated phosphatidyl-myo-inositols(PIM6); propose that, through this form of glycolipid editing, CD1e helps expand the repertoire of glycolipidic T cell antigens to optimize immune response (PMID:16311334)
• Data show that ubiquitination of CD1e appears to trigger its exit from Golgi compartments and its transport to endosomes. (PMID:18208508)
• A polymorphism related to the capacity of the CD1E molecule to participate in the immune response to complex glycolipids is discovered in individuals who might display a CD1e-altered immune response to complex glycolipid antigens. (PMID:18325888)
• SNPs in CD1A and CD1E were not associated with GBS susceptibility, specific clinical subgroups, anti-ganglioside antibodies, antecedent infections and prognosis. (PMID:18838176)
• CD1e propeptide is conserved during evolution, suggesting that it may also optimize the generation of CD1e molecules in other species. (PMID:19196239)
• CD1E and CD1A genes may be involved in networks which determine susceptibility to multiple sclerosis types RR-MS and PP-MS, respectively. (PMID:20954848)
• in the late endosomes/lysosomes of dendritic cells, the acid pH promotes the binding of lipid antigens to CD1e through increased hydrophobic and ionic interactions (PMID:21481186)
• CD1A and CD1E polymorphisms contribute to the polygenic susceptibility to multiple sclerosis (PMID:21496400)
• In Guillain-Barre syndrome, an initially positive association study with polymorphism of CD1A and CD1E genes was not confirmed (PMID:21696499)
• These data support that CD1e could have evolved to mediate lipid-exchange/editing processes. (PMID:21788486)
• CD1e may positively or negatively affect lipid presentation by CD1b, CD1c, and CD1d. (PMID:21844346)
• allelic variation in CD1E does not play a major role in determining multifocal motor neuropathy susceptibility. (PMID:22003931)
• Deciphering the role of CD1e protein in mycobacterial phosphatidyl-myo-inositol mannosides (PIM) processing for presentation by CD1b to T lymphocytes (PMID:22782895)
• The interaction of LAPTM5 with CD1e and their colocalization in antigen processing compartments both suggest that LAPTM5 might influence the role of CD1e in the presentation of lipid antigens. (PMID:22880058)
• for isoforms CD1b through CD1e, our simulations show the near-complete collapse of the hydrophobic cavities in the absence of the antigen. This event results from the spontaneous closure of the binding domain entrance, flanked by two alpha-helices. (PMID:23677998)
• There was no association between polymorphisms of CD1E genes and the susceptibilities to Guillain-Barre syndrome. (PMID:27653862)
• Single nucleotide polymorphisms in exon 2 of CD1A (*01/*02) and CD1E (*01/*02) cannot be recognized as a susceptibility or disease-causative factor for Guillain-Barre syndrome in the Bangladeshi population (PMID:29301656)
• CD1 gene polymorphism and susceptibility to celiac disease: Association of CD1E*02/02 in Moroccans. (PMID:32467040)

Cross-species orthologs

13 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
danio_rerio	mhc1lia	ENSDARG00000097766
danio_rerio		ENSDARG00000115781

Paralogs (22): HFE (ENSG00000010704), FCGRT (ENSG00000104870), ULBP1 (ENSG00000111981), ULBP2 (ENSG00000131015), ULBP3 (ENSG00000131019), MR1 (ENSG00000153029), RAET1L (ENSG00000155918), CD1D (ENSG00000158473), CD1A (ENSG00000158477), CD1C (ENSG00000158481), CD1B (ENSG00000158485), 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)

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
Pan troglodytes	Q4ACW4	98.2%	Diamond
Aotus nancymaae	Q5YB65	95.5%	Diamond
Mus musculus	P11609	94.3%	Diamond
Cavia porcellus	Q9QZY6	87.9%	Diamond
Rattus norvegicus	Q63493	83.6%	Diamond
Canis lupus familiaris	P18470	79.2%	Diamond
Ovis aries	P80943	79.2%	Diamond
Oryctolagus cuniculus	P20756	72.2%	Diamond
Sylvilagus floridanus	P23043	71.7%	Diamond
Sus scrofa	Q9XS72	63.0%	Diamond
Gallus gallus	P15979	47.2%	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
CD1A	protein-coding	909
CD1B	protein-coding	910
CD1C	protein-coding	911
OR10K2	protein-coding	391107
OR10T2	protein-coding	128360

Protein

Protein identifiers

T-cell surface glycoprotein CD1e, membrane-associated — P15812 (reviewed: P15812)

Alternative names: R2G1

All UniProt accessions (2): P15812, H0Y345

UniProt curated annotations — full annotation on UniProt →

Function. T-cell surface glycoprotein CD1e, soluble binds diacetylated lipids, including phosphatidyl inositides and diacylated sulfoglycolipids, and is required for the presentation of glycolipid antigens on the cell surface. The membrane-associated form is not active.

Subunit / interactions. Heterodimer with B2M (beta-2-microglobulin). The association with B2M appears to be facilitated by the presence of the propeptide.

Subcellular location. Golgi apparatus membrane. Early endosome. Late endosome Lysosome lumen.

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

Post-translational modifications. Mono-ubiquitinated. Proteolytically cleaved in late endosomes to yield a soluble form.

Polymorphism. Six alleles of CD1E are known. CD1E01 has His-102/Gln-106/Ser-149/Arg-164/Leu-194, CD1E02 has His-102/Arg-106/Ser-149/Arg-164/Leu-194, CD1E03 (9L) has His-102/Gln-106/Ser-149/Trp-164/Leu-194, CD1E04 (15L) has His-102/Gln-106/Ser-149/Arg-164/Pro-194, CD1E05 has Arg-102/Arg-106/Ser-149/Arg-164/Leu-194 and CD1E06 has His-102/Arg-106/Asn-149/Arg-164/Leu-194. The sequence shown is that of allele CD1E*01.

Isoforms (13)

UniProt ID	Names	Canonical?
P15812-1	1	yes
P15812-2	2
P15812-3	3
P15812-4	4
P15812-5	5
P15812-6	6
P15812-7	7
P15812-8	8
P15812-9	9
P15812-10	10
P15812-11	11
P15812-12	12
P15812-13	13

RefSeq proteins (13): NP_001036048, NP_001036049, NP_001036050, NP_001036051, NP_001036052, NP_001172036, NP_001172037, NP_001172039, NP_001172041, NP_001172042, NP_001172043, NP_001172044, NP_112155* (*=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 (56 total): strand 18, helix 8, splice variant 7, sequence variant 6, turn 6, chain 2, sequence conflict 2, glycosylation site 2, signal peptide 1, propeptide 1, transmembrane region 1, domain 1, disulfide bond 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
3S6C	Structure of human CD1e	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P15812-F1	81.66	0.66

Human Protein Atlas

Protein class: CD markers, Predicted membrane proteins, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): golgi apparatus; nucleoli

Antibody reliability (HPA): IH uncertain · 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.

Disulfide bonds (1)

Type	Positions
Disulfide bond	230–285

Glycosylation sites (2)

Type	Positions
N-linked (glcnac…) asparagine	47, 84

Function

Pathways and Gene Ontology

Reactome pathways

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

MSigDB gene sets: 175 (showing top): WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOCC_CELL_SURFACE, GOBP_LEUKOCYTE_MEDIATED_CYTOTOXICITY, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_VIA_MHC_CLASS_IB, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, PUJANA_CHEK2_PCC_NETWORK, BROWNE_HCMV_INFECTION_48HR_DN, GOBP_POSITIVE_REGULATION_OF_T_CELL_MEDIATED_CYTOTOXICITY, GOBP_REGULATION_OF_IMMUNE_RESPONSE, RUTELLA_RESPONSE_TO_CSF2RB_AND_IL4_UP, GOBP_LYMPHOCYTE_MEDIATED_IMMUNITY, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION, GOBP_REGULATION_OF_T_CELL_MEDIATED_CYTOTOXICITY

GO Biological Process (6): positive regulation of T cell mediated cytotoxicity (GO:0001916), adaptive immune response (GO:0002250), immune response (GO:0006955), 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 (4): endogenous lipid antigen binding (GO:0030883), exogenous lipid antigen binding (GO:0030884), lipopeptide binding (GO:0071723), lipid binding (GO:0008289)

GO Cellular Component (7): Golgi membrane (GO:0000139), early endosome (GO:0005769), late endosome (GO:0005770), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), lysosomal lumen (GO:0043202)

GO top-level categories

27 GO namespaces:

Category	Terms
antigen processing and presentation of lipid antigen via MHC class Ib	2
lipid antigen binding	2
endosome	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
immune response	1
immune system process	1
response to stimulus	1
antigen processing and presentation of endogenous antigen	1
antigen processing and presentation of exogenous antigen	1
biological_process	1
lipid binding	1
binding	1
Golgi apparatus	1
bounding membrane of organelle	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
lysosome	1
vacuolar lumen	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 18 annotations. The rest are phylogenetic / computational / electronic (IEA).

1 experimentally-supported GO terms:

GO term	NS	Evidence
Golgi apparatus	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 1,412 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD1E	CD207	Q9UJ71	934
CD1E	CD83	Q01151	856
CD1E	CD68	P34810	855
CD1E	CD5	P06127	789
CD1E	ITGAX	P20702	762
CD1E	CD86	P42081	749
CD1E	CD4	P01730	740
CD1E	MAN2B1	O00754	731
CD1E	CD80	P33681	719
CD1E	CD34	P28906	718
CD1E	CD7	P09564	718
CD1E	CD8A	P01732	718
CD1E	CD163	Q86VB7	710
CD1E	CSF2	P04141	701
CD1E	CD209	Q9NNX6	675

IntAct

Human interaction partners of CD1E in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

2 partners by confidence:

Partner	Interaction type	MIscore	Records
SUSD5	association	0.530	1
ADAM10	association	0.350	1

BioGRID (59 interactions; top human partners by supporting records): ABHD14A (Affinity Capture-MS; 2 records), B2M (Affinity Capture-MS; 2 records), BACE2 (Affinity Capture-MS; 2 records), C1QL1 (Affinity Capture-MS; 2 records), CANX (Affinity Capture-MS; 2 records), CTAGE5 (Affinity Capture-MS; 2 records), DPAGT1 (Affinity Capture-MS; 2 records), ENTPD7 (Affinity Capture-MS; 2 records), FAM69A (Affinity Capture-MS; 2 records), FCGRT (Affinity Capture-MS; 2 records), FNDC3A (Affinity Capture-MS; 2 records), ITGA7 (Affinity Capture-MS; 2 records), KCNJ8 (Affinity Capture-MS; 2 records), LMAN2L (Affinity Capture-MS; 2 records), MAN1A2 (Affinity Capture-MS; 2 records)

Disease & clinical

Genetic variants

Variant evidence for CD1E: 70 ClinVar records (1 pathogenic / likely pathogenic); 2 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	48
Likely benign	5
Benign	2

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
2685732	GRCh37/hg19 1q23.1-23.3(chr1:158001058-162858285)x1	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore CD1E’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; 23 predictions of 423):

Position(s)	Effect	Δscore	Sites
1:158354047–158354048	donor_loss	0.9900	5
1:158356757	acceptor_gain	0.9900
1:158354613	donor_gain	0.9500
1:158356117	donor_gain	0.9500
1:158355298–158355299	acceptor_loss	0.9400	6
1:158355293	acceptor_loss	0.9200
1:158356755	acceptor_gain	0.9200
1:158355570–158355571	donor_loss	0.9100	5
1:158356759	acceptor_gain	0.9100
1:158354048	donor_gain	0.8900

AlphaMissense

361 missense substitutions predicted likely pathogenic (of 2,519 scored), across 126 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
H289	8	0.881	0.968
F235	7	0.936	0.989
C230	7	0.935	0.963
C285	7	0.915	0.956
W244	7	0.907	0.983
F45	7	0.879	0.966
W80	7	0.856	0.949
W67	7	0.816	0.921
W267	7	0.811	0.921
W155	7	0.797	0.948
C129	7	0.780	0.862
S291	6	0.839	0.964
P211	6	0.802	0.918
F76	6	0.790	0.936
C190	6	0.790	0.887
P237	6	0.783	0.842
V287	6	0.710	0.851
D264	6	0.670	0.723
F37	5	0.839	0.871
F193	5	0.836	0.869

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	1.69e-05
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA)	favorable	9.58e-05

Disease associations

OMIM: gene MIM:188411 | disease phenotypes:

GWAS associations

2 associations:

Study	Trait	p-value
GCST003598_54	QRS duration	8e-9
GCST003598_53	QRS duration	1e-6

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression, affects response to substance, increases expression	1
abrine	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Endosulfan	decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment, decreases expression	1
Nickel	increases expression	1
Ozone	increases expression, increases abundance	1
Valproic Acid	decreases methylation	1

Clinical trials (associated diseases)

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

1 trials:

NCT	Phase	Status	Title
NCT07164248	Not specified	COMPLETED	Evaluation of Bone Mineral Density Indications and Outcomes in Female Adolescents: Implications for Early Detection of Osteopenia/Osteoporosis and Gynecologic Practice