CD300LB

Summary

CD300LB (CD300 molecule like family member b, HGNC:30811) is a protein-coding gene on chromosome 17q25.1, encoding CMRF35-like molecule 7 (A8K4G0). Acts as an activating immune receptor through its interaction with ITAM-bearing adapter TYROBP, and also independently by recruitment of GRB2.

CD300LB is a nonclassical activating receptor of the immunoglobulin (Ig) superfamily expressed on myeloid cells (Martinez-Barriocanal and Sayos, 2006 [PubMed 16920917]).

Source: NCBI Gene 124599 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 35 total
• MANE Select transcript: NM_174892

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30811
Approved symbol	CD300LB
Name	CD300 molecule like family member b
Location	17q25.1
Locus type	gene with protein product
Status	Approved
Aliases	TREM5, CLM7
Ensembl gene	ENSG00000178789
Ensembl biotype	protein_coding
OMIM	610705
Entrez	124599

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000314401, ENST00000392621, ENST00000718280

RefSeq mRNA: 1 — MANE Select: NM_174892 NM_174892

CCDS: CCDS11700

Canonical transcript exons

ENST00000392621 — 4 exons

Exon	Start	End
ENSE00001272479	74523579	74523651
ENSE00001272487	74525748	74526077
ENSE00001272501	74531311	74531475
ENSE00004034617	74521174	74522900

Expression profiles

Bgee: expression breadth ubiquitous, 136 present calls, max score 94.42.

FANTOM5 (CAGE): breadth broad, TPM avg 1.6675 / max 108.8089, expressed in 211 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
167946	1.1430	177
167944	0.3174	113
167945	0.2070	90

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	94.42	gold quality
leukocyte	CL:0000738	94.17	gold quality
granulocyte	CL:0000094	92.43	gold quality
blood	UBERON:0000178	85.95	gold quality
vermiform appendix	UBERON:0001154	76.93	gold quality
bone marrow cell	CL:0002092	74.07	gold quality
caecum	UBERON:0001153	72.47	gold quality
bone marrow	UBERON:0002371	72.35	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	71.38	silver quality
gall bladder	UBERON:0002110	67.80	gold quality
tibia	UBERON:0000979	65.54	gold quality
spleen	UBERON:0002106	65.42	gold quality
myocardium	UBERON:0002349	65.12	gold quality
esophagus squamous epithelium	UBERON:0006920	64.98	gold quality
right lung	UBERON:0002167	64.00	gold quality
smooth muscle tissue	UBERON:0001135	63.24	gold quality
cerebellar vermis	UBERON:0004720	62.48	gold quality
amniotic fluid	UBERON:0000173	61.88	gold quality
upper lobe of left lung	UBERON:0008952	61.71	gold quality
rectum	UBERON:0001052	61.63	gold quality
decidua	UBERON:0002450	61.55	gold quality
parotid gland	UBERON:0001831	61.41	gold quality
trabecular bone tissue	UBERON:0002483	61.35	gold quality
nasal cavity epithelium	UBERON:0005384	61.15	gold quality
quadriceps femoris	UBERON:0001377	61.04	gold quality
right coronary artery	UBERON:0001625	60.67	gold quality
vastus lateralis	UBERON:0001379	60.66	gold quality
tendon of biceps brachii	UBERON:0008188	60.50	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	60.21	gold quality
epithelium of nasopharynx	UBERON:0001951	60.01	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.11

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

47 targeting CD300LB, 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-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-3913-3P	99.74	66.53	938
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-324-3P	99.26	66.31	1034
HSA-MIR-499A-3P	99.18	69.20	1392
HSA-MIR-499B-3P	99.18	69.27	1391
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-548AS-3P	99.12	69.12	2294
HSA-MIR-7160-5P	99.11	67.17	2207

Literature-anchored findings (GeneRIF, showing 5)

• CD300b defines a nonclassical Ig receptor able to trigger signals by coupling distinct mediators and thus initiating different signaling pathways (PMID:16920917)
• although both mouse and human LMIR5 play activatory roles in innate immunity cells, the functions of LMIR5 were differentially regulated in mouse versus human cells. (PMID:17928527)
• 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)
• this paper identified CD300b as an lipopolysaccharide-recognizing receptor that regulated TLR4 signaling (PMID:27261276)
• CD300LB expression is significantly upregulated in human masticatory mucosa during wound healing (PMID:28005267)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cd300lb	ENSMUSG00000063193
rattus_norvegicus	Cd300lb	ENSRNOG00000070190

Paralogs (13): TREM2 (ENSG00000095970), TMIGD3 (ENSG00000121933), CD300LG (ENSG00000161649), TREML1 (ENSG00000161911), FCMR (ENSG00000162894), PIGR (ENSG00000162896), FCAMR (ENSG00000162897), CD300C (ENSG00000167850), CD300A (ENSG00000167851), CD300LF (ENSG00000186074), CD300E (ENSG00000186407), CD300LD (ENSG00000204345), CD300H (ENSG00000284690)

Protein

Protein identifiers

CMRF35-like molecule 7 — A8K4G0 (reviewed: A8K4G0)

Alternative names: CD300 antigen-like family member B, CMRF35-A2, Immune receptor expressed on myeloid cells 3, Leukocyte mono-Ig-like receptor 5, Triggering receptor expressed on myeloid cells 5

All UniProt accessions (2): A8K4G0, J9JID3

UniProt curated annotations — full annotation on UniProt →

Function. Acts as an activating immune receptor through its interaction with ITAM-bearing adapter TYROBP, and also independently by recruitment of GRB2.

Subunit / interactions. Interacts with TYROBP, which enhances cell surface expression and activation properties. Interacts with GRB2 in the presence of FYN.

Subcellular location. Cell membrane.

Tissue specificity. Expressed exclusively in myeloid lineages.

Post-translational modifications. Phosphorylation on Tyr-188 by FYN is required for interaction with GRB2.

Similarity. Belongs to the CD300 family.

RefSeq proteins (1): NP_777552* (*=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 (12 total): mutagenesis site 2, topological domain 2, signal peptide 1, chain 1, sequence conflict 1, transmembrane region 1, domain 1, site 1, modified residue 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A8K4G0-F1	80.23	0.59

Functional residue map

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

Catalytic / active sites (1): 158 (interaction with tyrobp)

Post-translational modifications (1): 188

Disulfide bonds (1): 36–104

Mutagenesis-validated functional residues (2):

Position	Phenotype
188	no effect on interaction with tyrobp, but strongly reduces activation properties.
158	abolishes interaction with tyrobp, and strongly reduces activation properties.

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: 90 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, GSE45365_NK_CELL_VS_CD11B_DC_DN, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_IMMUNE_RESPONSE, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, NIKOLSKY_BREAST_CANCER_17Q21_Q25_AMPLICON, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, GSE13522_WT_VS_IFNG_KO_SKIN_DN, GOBP_ACTIVATION_OF_IMMUNE_RESPONSE, GOBP_IMMUNE_RESPONSE_REGULATING_SIGNALING_PATHWAY, ZHOU_INFLAMMATORY_RESPONSE_FIMA_DN, REACTOME_DAP12_INTERACTIONS, SUPT16H_TARGET_GENES, GSE11057_PBMC_VS_MEM_CD4_TCELL_UP

GO Biological Process (2): immune response-activating signaling pathway (GO:0002757), immune system process (GO:0002376)

GO Molecular Function (3): transmembrane signaling receptor activity (GO:0004888), identical protein binding (GO:0042802), 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
activation of immune response	1
immune response-regulating signaling pathway	1
biological_process	1
signaling receptor activity	1
protein binding	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1044 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD300LB	TYROBP	O43914	907
CD300LB	HCST	Q9UBK5	795
CD300LB	FCER1G	P30273	721
CD300LB	NAT9	Q9BTE0	636
CD300LB	TIMD4	Q96H15	622
CD300LB	CARD14	Q9BXL6	536
CD300LB	SLC22A4	Q9H015	511
CD300LB	ZNF614	Q8N883	491
CD300LB	RPTOR	Q8N122	469
CD300LB	CCNYL1	Q8N7R7	451
CD300LB	CLRN3	Q8NCR9	449
CD300LB	ESCO1	Q5FWF5	436
CD300LB	TUBG2	Q9NRH3	431
CD300LB	ESCO2	Q56NI9	430
CD300LB	RDX	P35241	429

IntAct

27 interactions, top by confidence:

A	B	Type	Score
CD300LB	CD300C	psi-mi:“MI:0915”(physical association)	0.590
CD300LB	CD300LF	psi-mi:“MI:0915”(physical association)	0.590
CD300LB	CD300E	psi-mi:“MI:0915”(physical association)	0.590
CD300A	CD300LB	psi-mi:“MI:0915”(physical association)	0.590
CD300LB	CD300LB	psi-mi:“MI:0915”(physical association)	0.590
CD300C	CD300LB	psi-mi:“MI:0915”(physical association)	0.590
CD300LF	CD300LB	psi-mi:“MI:0915”(physical association)	0.590
CD300LB	CD300LD	psi-mi:“MI:0915”(physical association)	0.590
CD300LB	CD300A	psi-mi:“MI:0915”(physical association)	0.590
LILRA1	CD300LB	psi-mi:“MI:0915”(physical association)	0.400
CD300LB	SIGLEC10	psi-mi:“MI:0915”(physical association)	0.400
CD300LB	SIGLEC14	psi-mi:“MI:0915”(physical association)	0.400
CD300LB	SIGLEC5	psi-mi:“MI:0915”(physical association)	0.400
CD300LB	SIGLEC6	psi-mi:“MI:0915”(physical association)	0.400
CD300LB	RAD51B	psi-mi:“MI:0914”(association)	0.350

BioGRID (6): CD300LB (Affinity Capture-MS), DDX19B (Affinity Capture-MS), RAD51B (Affinity Capture-MS), ATP13A1 (Affinity Capture-MS), ATP2B2 (Affinity Capture-MS), APP (Reconstituted Complex)

ESM2 similar proteins: A0A0E4BZH1, A4QPC6, A5D7V5, A7TZE6, A7TZF0, A7TZF3, A7XUX6, A7XV04, A7XV07, A8K4G0, A8MVZ5, O70355, P08508, P18892, P24071, P31994, P55803, P78410, P79391, Q13410, Q16653, Q29ZQ1, Q3KPI0, Q58DF9, Q5R7W8, Q5R960, Q5R996, Q61885, Q62556, Q63345, Q6Q8B3, Q6UXZ3, Q6XJV4, Q6XJV6, Q7KYR7, Q7TST0, Q7YR73, Q8BTP3, Q8K249, Q8TD46

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, G3X8R9, O95944, P0DMS9, Q2LA85, Q86YW5, Q8K558, A1KXC4, O60667, Q29244, Q2TB54, Q5M871, Q5R770

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
FYN	“up-regulates activity”	CD300LB	phosphorylation
CD300LB	“up-regulates activity”	GRB2	binding
CD300LB	“up-regulates activity”	TYROBP	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 11 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	8	69.7×	2e-13

GO biological processes:

GO term	Partners	Fold	FDR
cell adhesion	5	17.0×	5e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	26
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

520 predictions. Top by Δscore:

Variant	Effect	Δscore
17:74523574:CTCA:C	donor_loss	1.0000
17:74523575:TCA:T	donor_loss	1.0000
17:74523576:CAC:C	donor_loss	1.0000
17:74523578:C:CT	donor_loss	1.0000
17:74523648:CCCT:C	acceptor_gain	1.0000
17:74523649:CCTC:C	acceptor_gain	1.0000
17:74523650:CT:C	acceptor_gain	1.0000
17:74523652:C:CC	acceptor_gain	1.0000
17:74531307:TCA:T	donor_loss	1.0000
17:74531308:CACC:C	donor_loss	1.0000
17:74531309:ACCTG:A	donor_loss	1.0000
17:74523577:A:AC	donor_gain	0.9900
17:74523578:C:CC	donor_gain	0.9900
17:74523647:TCCCT:T	acceptor_gain	0.9900
17:74523648:CCCTC:C	acceptor_gain	0.9900
17:74523651:TC:T	acceptor_loss	0.9900
17:74523653:T:A	acceptor_loss	0.9900
17:74523657:C:CT	acceptor_gain	0.9900
17:74523659:C:CT	acceptor_gain	0.9900
17:74523660:A:T	acceptor_gain	0.9900
17:74525744:TTACC:T	donor_loss	0.9900
17:74525745:TA:T	donor_loss	0.9900
17:74525746:A:AT	donor_loss	0.9900
17:74525747:C:CA	donor_loss	0.9900
17:74531309:A:AC	donor_gain	0.9900
17:74531310:C:CC	donor_gain	0.9900
17:74522901:C:CC	acceptor_gain	0.9800
17:74522901:CTG:C	acceptor_loss	0.9800
17:74522902:T:A	acceptor_loss	0.9800
17:74523578:CCT:C	donor_gain	0.9800

AlphaMissense

1311 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:74525977:C:A	K47N	0.994
17:74525977:C:G	K47N	0.994
17:74525971:C:A	W49C	0.987
17:74525971:C:G	W49C	0.987
17:74525807:C:G	C104S	0.985
17:74525808:A:T	C104S	0.985
17:74525979:T:C	K47E	0.983
17:74526011:C:G	C36S	0.983
17:74526012:A:T	C36S	0.983
17:74525953:C:A	W55C	0.976
17:74525953:C:G	W55C	0.976
17:74525969:C:G	C50S	0.976
17:74525970:A:T	C50S	0.976
17:74525973:A:G	W49R	0.976
17:74525973:A:T	W49R	0.976
17:74525974:C:A	W48C	0.976
17:74525974:C:G	W48C	0.976
17:74525814:A:C	Y102D	0.974
17:74525978:T:G	K47T	0.970
17:74525809:C:A	W103C	0.967
17:74525809:C:G	W103C	0.967
17:74525978:T:A	K47M	0.964
17:74525880:C:G	D80H	0.963
17:74526012:A:G	C36R	0.963
17:74525808:A:G	C104R	0.961
17:74525968:G:C	C50W	0.956
17:74525992:C:A	W42C	0.956
17:74525992:C:G	W42C	0.956
17:74525979:T:G	K47Q	0.955
17:74525807:C:T	C104Y	0.954

dbSNP variants (sampled 300 via entrez): RS1000120558 (17:74528703 T>C), RS1000227885 (17:74532275 G>A,T), RS1000343500 (17:74532457 G>C,T), RS1000477831 (17:74521782 C>G,T), RS1000615145 (17:74530960 G>A), RS1000853987 (17:74527100 C>T), RS1001234446 (17:74532239 C>T), RS1001280724 (17:74526725 AG>A), RS1001385768 (17:74527807 C>A,T), RS1001656320 (17:74522663 G>A), RS1002228559 (17:74533269 C>G), RS1002951271 (17:74525501 C>T), RS1003249959 (17:74532296 G>C), RS1003287927 (17:74523859 T>C), RS1003313132 (17:74530887 T>C)

Disease associations

OMIM: gene MIM:610705 | 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
GCST008478_45	Neurological blood protein biomarker levels	5.000000e-31

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
sodium arsenite	increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, affects response to substance, increases expression, affects cotreatment	1
gallium arsenide	increases expression	1
di-n-butylphosphoric acid	affects expression	1
Am 580	increases expression	1
abrine	increases expression	1
Rosiglitazone	increases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment, decreases expression	1
Tretinoin	increases expression	1
Cadmium Chloride	increases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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