CD300E

Summary

CD300E (CD300e molecule, HGNC:28874) is a protein-coding gene on chromosome 17q25.1, encoding CMRF35-like molecule 2 (Q496F6). Probably acts as an activating receptor.

This gene encodes a member of the CD300 glycoprotein family of cell surface proteins expressed on myeloid cells. The protein interacts with the TYRO protein tyrosine kinase-binding protein and is thought to act as an activating receptor.

Source: NCBI Gene 342510 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 27 total
• MANE Select transcript: NM_181449

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28874
Approved symbol	CD300E
Name	CD300e molecule
Location	17q25.1
Locus type	gene with protein product
Status	Approved
Aliases	IREM2, CLM2
Ensembl gene	ENSG00000186407
Ensembl biotype	protein_coding
OMIM	609801
Entrez	342510

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000392619, ENST00000412268, ENST00000961099

RefSeq mRNA: 1 — MANE Select: NM_181449 NM_181449

CCDS: CCDS11702

Canonical transcript exons

ENST00000392619 — 4 exons

Exon	Start	End
ENSE00001332588	74609885	74612773
ENSE00001512513	74623582	74623738
ENSE00001662130	74617118	74617465
ENSE00004034827	74613925	74614033

Expression profiles

Bgee: expression breadth ubiquitous, 124 present calls, max score 98.55.

FANTOM5 (CAGE): breadth broad, TPM avg 12.0858 / max 1652.2842, expressed in 186 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
167979	3.4404	128
167976	3.3552	121
167980	2.5581	82
167977	1.3949	95
167978	1.3052	101
167981	0.0320	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	98.55	gold quality
leukocyte	CL:0000738	98.39	gold quality
granulocyte	CL:0000094	97.66	gold quality
blood	UBERON:0000178	92.77	gold quality
vermiform appendix	UBERON:0001154	86.98	gold quality
right lung	UBERON:0002167	84.60	gold quality
bone marrow	UBERON:0002371	84.32	gold quality
upper lobe of left lung	UBERON:0008952	80.88	gold quality
bone marrow cell	CL:0002092	79.87	gold quality
sural nerve	UBERON:0015488	78.40	gold quality
spleen	UBERON:0002106	78.03	gold quality
lung	UBERON:0002048	75.45	gold quality
smooth muscle tissue	UBERON:0001135	71.77	gold quality
gall bladder	UBERON:0002110	69.66	gold quality
left uterine tube	UBERON:0001303	69.57	gold quality
placenta	UBERON:0001987	68.64	gold quality
right coronary artery	UBERON:0001625	67.27	gold quality
omental fat pad	UBERON:0010414	67.02	gold quality
descending thoracic aorta	UBERON:0002345	66.07	gold quality
left adrenal gland cortex	UBERON:0035825	65.45	gold quality
adipose tissue	UBERON:0001013	64.95	gold quality
right adrenal gland	UBERON:0001233	64.75	gold quality
left adrenal gland	UBERON:0001234	64.51	gold quality
subcutaneous adipose tissue	UBERON:0002190	63.04	gold quality
lymph node	UBERON:0000029	62.75	gold quality
right atrium auricular region	UBERON:0006631	62.75	gold quality
right adrenal gland cortex	UBERON:0035827	62.13	gold quality
adrenal gland	UBERON:0002369	62.00	gold quality
left coronary artery	UBERON:0001626	61.94	gold quality
thoracic aorta	UBERON:0001515	61.78	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8498	yes	1716.25
E-CURD-122	yes	35.97
E-MTAB-9221	yes	27.52
E-ANND-3	yes	19.65
E-MTAB-9067	yes	4.61

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

87 targeting CD300E, 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-6873-3P	100.00	71.42	2626
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-4441	99.49	66.56	3216

Literature-anchored findings (GeneRIF, showing 4)

• IREM-2 is a novel activating immunoglobulin-like receptor expressed on mature hemopoietic cells of the monocytic and myeloid dendritic cell lineages. (PMID:15557162)
• CD300 molecules are all expressed by DC; CD300b, d, e and f are restricted to different subpopulations of the myeloid DC lineage. They have been shown to regulate DC function both in vitro and in vivo. (PMID:23072861)
• CD300E expression is significantly upregulated in human masticatory mucosa during wound healing (PMID:28005267)
• The immune receptor CD300e negatively regulates T cell activation by impairing the STAT1-dependent antigen presentation. (PMID:33020563)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cd300e	ENSMUSG00000048498
rattus_norvegicus	Cd300e	ENSRNOG00000036726

Paralogs (13): TREM2 (ENSG00000095970), TMIGD3 (ENSG00000121933), CD300LG (ENSG00000161649), TREML1 (ENSG00000161911), FCMR (ENSG00000162894), PIGR (ENSG00000162896), FCAMR (ENSG00000162897), CD300C (ENSG00000167850), CD300A (ENSG00000167851), CD300LB (ENSG00000178789), CD300LF (ENSG00000186074), CD300LD (ENSG00000204345), CD300H (ENSG00000284690)

Protein

Protein identifiers

CMRF35-like molecule 2 — Q496F6 (reviewed: Q496F6)

Alternative names: CD300 antigen-like family member E, CMRF35-A5, Immune receptor expressed on myeloid cells 2, Polymeric immunoglobulin receptor 2

All UniProt accessions (2): C9JDD2, Q496F6

UniProt curated annotations — full annotation on UniProt →

Function. Probably acts as an activating receptor.

Subunit / interactions. Interacts with TYROBP.

Subcellular location. Cell membrane.

Tissue specificity. Present on the surface of mature hematopoietic cells of the monocyte and myeloid lineages (at protein level).

Post-translational modifications. N-glycosylated.

Similarity. Belongs to the CD300 family.

RefSeq proteins (1): NP_852114* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR050671	CD300_family_receptors	Family

Pfam: PF07686

UniProt features (11 total): sequence variant 3, topological domain 2, signal peptide 1, chain 1, transmembrane region 1, domain 1, glycosylation site 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q496F6-F1	78.04	0.48

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): 36–104

Glycosylation sites (1): 154

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-198933	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-2172127	DAP12 interactions

MSigDB gene sets: 62 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOCC_CELL_SURFACE, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_REGULATION_OF_DEFENSE_RESPONSE, NIKOLSKY_BREAST_CANCER_17Q21_Q25_AMPLICON, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, BOSCO_TH1_CYTOTOXIC_MODULE, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, REACTOME_DAP12_INTERACTIONS, MIR4668_5P

GO Biological Process (3): immune system process (GO:0002376), signal transduction (GO:0007165), regulation of innate immune response (GO:0045088)

GO Molecular Function (2): transmembrane signaling receptor activity (GO:0004888), protein binding (GO:0005515)

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

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Adaptive Immune System	1
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
biological_process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
regulation of response to biotic stimulus	1
regulation of defense response	1
regulation of response to external stimulus	1
innate immune response	1
regulation of immune response	1
signaling receptor activity	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

664 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD300E	FCER1G	P30273	811
CD300E	TYROBP	O43914	655
CD300E	HCST	Q9UBK5	494
CD300E	CD247	P20963	494
CD300E	FCGR1A	P12314	436
CD300E	RAB3B	P20337	429
CD300E	CD33	P20138	380
CD300E	FCGR3B	O75015	359
CD300E	FCGR3A	P08637	349
CD300E	CD7	P09564	329
CD300E	BTBD17	A6NE02	327
CD300E	ANPEP	P15144	324
CD300E	SCARB2	Q14108	308
CD300E	CD36	P16671	307
CD300E	CR1	P17927	303

IntAct

21 interactions, top by confidence:

A	B	Type	Score
CD300LB	CD300E	psi-mi:“MI:0915”(physical association)	0.590
CTXN3	CD300E	psi-mi:“MI:0915”(physical association)	0.560
TUSC5	CD300E	psi-mi:“MI:0915”(physical association)	0.560
CD300E	STX8	psi-mi:“MI:0915”(physical association)	0.560
CD300E	CTXN3	psi-mi:“MI:0915”(physical association)	0.560
CD300E	SPPL2B	psi-mi:“MI:0914”(association)	0.530
CD300E	CD300LF	psi-mi:“MI:0915”(physical association)	0.400
CD300A	CD300E	psi-mi:“MI:0915”(physical association)	0.400
CD300E	CD300E	psi-mi:“MI:0915”(physical association)	0.400
CD300E	CD300LD	psi-mi:“MI:0915”(physical association)	0.400
CD300C	CD300E	psi-mi:“MI:0915”(physical association)	0.400
CD300E	E6	psi-mi:“MI:0915”(physical association)	0.370
CD300E	HLA-A	psi-mi:“MI:0914”(association)	0.350
CD300E	RAP1B	psi-mi:“MI:0914”(association)	0.350
STX8	CD300E	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (15): TMEM67 (Affinity Capture-MS), SPPL2B (Affinity Capture-MS), PKD2 (Affinity Capture-MS), ATF6 (Affinity Capture-MS), CD300E (Two-hybrid), CD300E (Two-hybrid), CTXN3 (Two-hybrid), POMT2 (Affinity Capture-MS), SPPL2B (Affinity Capture-MS), SERPINA10 (Affinity Capture-MS), RMDN1 (Affinity Capture-MS), LYPLAL1 (Affinity Capture-MS), CLYBL (Affinity Capture-MS), RAP1B (Affinity Capture-MS), CD300E (Two-hybrid)

ESM2 similar proteins: A0A0K2S4Q6, A2A7V7, A6NI73, A8K4G0, O43699, O75019, O75022, O75023, O75871, O76036, P0C191, P20138, P24071, P40198, P59901, P80943, Q08708, Q13410, Q28110, Q3U497, Q496F6, Q64JA4, Q6GTX8, Q6ISS4, Q6PI73, Q6UXZ3, Q7TSN2, Q863H2, Q8C567, Q8K249, Q8MJZ2, Q8MJZ7, Q8N149, Q8N423, Q8N6C8, Q8NHJ6, Q8NHL6, Q8VBT3, Q8VCH2, Q95JB9

Diamond homologs: A0A0K2S4Q6, A2A7V7, A2TGX5, A5D7B2, A8K4G0, O70570, P01832, P01833, P0DUB1, P15083, P81265, Q08708, Q1ERP8, Q3LRV9, Q3U497, Q496F6, Q566E6, Q6SJQ0, Q6SJQ5, Q6SJQ7, Q6UXG3, Q6UXZ3, Q7TSN2, Q8K249, Q8TDQ1, Q8VCH2, Q99NH8, Q9UGN4, O95944, Q2TB54, G3X8R9, P0DMS9, Q2LA85, O60667, Q86YW5, Q8K558, A1KXC4, Q29244, Q5M871, Q5R770

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

472 predictions. Top by Δscore:

Variant	Effect	Δscore
17:74613919:GCTTA:G	donor_loss	1.0000
17:74613920:CTTAC:C	donor_loss	1.0000
17:74613921:TTACC:T	donor_loss	1.0000
17:74613922:TACC:T	donor_loss	1.0000
17:74613923:A:AT	donor_loss	1.0000
17:74613923:AC:A	donor_gain	1.0000
17:74613924:CC:C	donor_gain	1.0000
17:74614029:AATTG:A	acceptor_gain	1.0000
17:74614030:ATTG:A	acceptor_gain	1.0000
17:74614031:TTG:T	acceptor_gain	1.0000
17:74614032:TG:T	acceptor_gain	1.0000
17:74614033:GCT:G	acceptor_loss	1.0000
17:74614034:C:CC	acceptor_gain	1.0000
17:74614035:T:C	acceptor_loss	1.0000
17:74614037:T:TC	acceptor_gain	1.0000
17:74623579:CA:C	donor_loss	1.0000
17:74612774:C:CA	acceptor_loss	0.9900
17:74612775:T:G	acceptor_loss	0.9900
17:74613923:A:AC	donor_gain	0.9900
17:74613923:ACC:A	donor_gain	0.9900
17:74613924:C:CC	donor_gain	0.9900
17:74613924:CCC:C	donor_gain	0.9900
17:74613924:CCCTG:C	donor_gain	0.9900
17:74613947:C:A	donor_gain	0.9900
17:74614037:T:C	acceptor_gain	0.9900
17:74623580:A:AC	donor_gain	0.9900
17:74623581:C:CC	donor_gain	0.9900
17:74623581:CCT:C	donor_gain	0.9900
17:74623581:CCTGA:C	donor_gain	0.9900
17:74612774:C:CC	acceptor_gain	0.9800

AlphaMissense

1305 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:74617359:C:A	W49C	0.986
17:74617359:C:G	W49C	0.986
17:74617365:C:A	K47N	0.986
17:74617365:C:G	K47N	0.986
17:74617195:C:G	C104S	0.972
17:74617196:A:T	C104S	0.972
17:74617399:C:G	C36S	0.970
17:74617400:A:T	C36S	0.970
17:74617361:A:G	W49R	0.968
17:74617361:A:T	W49R	0.968
17:74617357:C:G	C50S	0.966
17:74617358:A:T	C50S	0.966
17:74617393:T:C	Y38C	0.965
17:74617367:T:C	K47E	0.964
17:74617202:A:C	Y102D	0.951
17:74617246:A:G	F87S	0.946
17:74617366:T:G	K47T	0.945
17:74617273:A:G	I78T	0.942
17:74617333:C:G	C58S	0.942
17:74617334:A:T	C58S	0.942
17:74617273:A:T	I78N	0.939
17:74617366:T:A	K47M	0.938
17:74617196:A:G	C104R	0.936
17:74617225:A:T	L94H	0.936
17:74617240:A:T	V89E	0.935
17:74617189:A:G	I106T	0.934
17:74617195:C:T	C104Y	0.934
17:74617333:C:T	C58Y	0.934
17:74617201:T:C	Y102C	0.933
17:74617367:T:G	K47Q	0.933

dbSNP variants (sampled 300 via entrez): RS1000060453 (17:74621853 C>A), RS1000594562 (17:74614857 T>C,G), RS1000705097 (17:74620462 T>A), RS1000844062 (17:74624646 T>C,G), RS1000946560 (17:74614124 C>T), RS1000986561 (17:74618792 C>G), RS1001089091 (17:74609721 T>A), RS1001424027 (17:74609998 C>T), RS1001527671 (17:74614593 C>A), RS1001643461 (17:74618442 A>T), RS1001828823 (17:74624553 C>G), RS1001983585 (17:74619826 G>A), RS1002062062 (17:74614780 C>T), RS1002334812 (17:74618280 T>G), RS1002449150 (17:74618428 CAAT>C)

Disease associations

OMIM: gene MIM:609801 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006585_957	Blood protein levels	4.000000e-27
GCST009266_15	Dental caries (decayed and filled deciduous tooth surfaces)	4.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
TL8-506	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
(+)-JQ1 compound	decreases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression, increases abundance	1
Triclosan	increases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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