CD300LD

Summary

CD300LD (CD300 molecule like family member d, HGNC:16848) is a protein-coding gene on chromosome 17q25.1, encoding CMRF35-like molecule 5 (Q6UXZ3).

Predicted to enable transmembrane signaling receptor activity and virus receptor activity. Predicted to be involved in immune response-activating signaling pathway. Predicted to act upstream of or within regulation of interleukin-6 production and regulation of tumor necrosis factor production. Predicted to be active in plasma membrane.

Source: NCBI Gene 100131439 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 33 total
• MANE Select transcript: NM_001115152

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16848
Approved symbol	CD300LD
Name	CD300 molecule like family member d
Location	17q25.1
Locus type	gene with protein product
Status	Approved
Aliases	CMRF35A4, CD300D
Ensembl gene	ENSG00000204345
Ensembl biotype	protein_coding
OMIM	616301
Entrez	100131439

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000375352

RefSeq mRNA: 1 — MANE Select: NM_001115152 NM_001115152

CCDS: CCDS42379

Canonical transcript exons

ENST00000375352 — 4 exons

Exon	Start	End
ENSE00001466790	74579365	74580113
ENSE00001466793	74582218	74582311
ENSE00001466800	74592163	74592283
ENSE00002457515	74588511	74588849

Expression profiles

Bgee: expression breadth tissue_specific, 10 present calls, max score 61.82.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	61.82	gold quality
leukocyte	CL:0000738	54.84	gold quality
monocyte	CL:0000576	54.80	gold quality
granulocyte	CL:0000094	53.53	gold quality
bone marrow cell	CL:0002092	49.71	gold quality
bone marrow	UBERON:0002371	48.50	gold quality
vermiform appendix	UBERON:0001154	45.75	gold quality
sural nerve	UBERON:0015488	43.89	gold quality
colonic epithelium	UBERON:0000397	42.31	gold quality
ganglionic eminence	UBERON:0004023	37.43	gold quality
apex of heart	UBERON:0002098	36.84	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
spleen	UBERON:0002106	35.90	gold quality
rectum	UBERON:0001052	35.23	gold quality
mucosa of stomach	UBERON:0001199	35.05	gold quality
right coronary artery	UBERON:0001625	34.92	gold quality
right lung	UBERON:0002167	33.63	gold quality
muscle tissue	UBERON:0002385	33.40	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
liver	UBERON:0002107	32.75	gold quality
gall bladder	UBERON:0002110	31.38	gold quality
right adrenal gland cortex	UBERON:0035827	30.86	gold quality
left uterine tube	UBERON:0001303	30.75	silver quality
lymph node	UBERON:0000029	30.57	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
right adrenal gland	UBERON:0001233	29.60	gold quality
prefrontal cortex	UBERON:0000451	29.54	gold quality
placenta	UBERON:0001987	29.36	gold quality
small intestine	UBERON:0002108	28.73	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.96

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• the function of CD300d would be related to the regulation of the expression of other CD300 molecules and the composition of CD300 complexes on the cell surface. (PMID:22291008)
• 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)
• CD300ld on neutrophils is required for tumour-driven immune suppression. (PMID:37674079)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cd300a	ENSMUSG00000034652

Paralogs (13): TREM2 (ENSG00000095970), TMIGD3 (ENSG00000121933), CD300LG (ENSG00000161649), TREML1 (ENSG00000161911), FCMR (ENSG00000162894), PIGR (ENSG00000162896), FCAMR (ENSG00000162897), CD300C (ENSG00000167850), CD300A (ENSG00000167851), CD300LB (ENSG00000178789), CD300LF (ENSG00000186074), CD300E (ENSG00000186407), CD300H (ENSG00000284690)

Protein

Protein identifiers

CMRF35-like molecule 5 — Q6UXZ3 (reviewed: Q6UXZ3)

Alternative names: CD300 antigen-like family member D, CMRF35-A4

All UniProt accessions (1): Q6UXZ3

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Forms complexes with the CD300 family members with exception of CD300c.

Subcellular location. Cell membrane.

Tissue specificity. Expression seems restricted to cells of myeloid lineage.

Post-translational modifications. N-glycosylated.

Similarity. Belongs to the CD300 family.

RefSeq proteins (1): NP_001108624* (*=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): topological domain 2, sequence variant 2, signal peptide 1, chain 1, mutagenesis site 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-Q6UXZ3-F1	80.81	0.56

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): 39–107

Glycosylation sites (1): 28

Mutagenesis-validated functional residues (1):

Position	Phenotype
158	unable to reach the cell surface upon transfection.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 54 (showing top): REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_IMMUNE_RESPONSE, COATES_MACROPHAGE_M1_VS_M2_DN, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, GOBP_ACTIVATION_OF_IMMUNE_RESPONSE, GOBP_IMMUNE_RESPONSE_REGULATING_SIGNALING_PATHWAY, MTOR_UP.V1_UP, TERF1_TARGET_GENES, GSE11924_TH1_VS_TH2_CD4_TCELL_DN, GSE11924_TH2_VS_TH17_CD4_TCELL_UP, GSE17721_CTRL_VS_LPS_12H_BMDC_UP, GSE17721_CTRL_VS_GARDIQUIMOD_24H_BMDC_UP, GSE17721_PAM3CSK4_VS_CPG_8H_BMDC_UP, GSE17721_CPG_VS_GARDIQUIMOD_24H_BMDC_DN, GOBP_POSITIVE_REGULATION_OF_IMMUNE_SYSTEM_PROCESS

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

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-1 pathways:

Category	Pathways
Adaptive 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
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

282 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD300LD	F11R	Q9Y624	690
CD300LD	FCER1G	P30273	580
CD300LD	CD300LF	Q8TDQ1	462
CD300LD	NPIPA7	E9PJI5	447
CD300LD	BTBD17	A6NE02	419
CD300LD	CXADR	P78310	406
CD300LD	GPR142	Q7Z601	396
CD300LD	A0A0J9YYA3	A0A0J9YYA3	391
CD300LD	TNS3	Q68CZ2	377
CD300LD	NECTIN1	Q15223	372
CD300LD	CD55	P08174	370
CD300LD	GLDN	Q6ZMI3	353
CD300LD	NCAM1	P13591	353
CD300LD	DHODH	Q02127	352
CD300LD	ICAM1	P05362	350

IntAct

13 interactions, top by confidence:

A	B	Type	Score
CD300LB	CD300LD	psi-mi:“MI:0915”(physical association)	0.590
CD300LD	TFF1	psi-mi:“MI:0915”(physical association)	0.540
TFF1	CD300LD	psi-mi:“MI:0407”(direct interaction)	0.540
CD300LD	VIM	psi-mi:“MI:0915”(physical association)	0.400
FCER1G	CD300LD	psi-mi:“MI:0915”(physical association)	0.400
TYROBP	CD300LD	psi-mi:“MI:0915”(physical association)	0.400
CD300A	CD300LD	psi-mi:“MI:0915”(physical association)	0.400
CD300E	CD300LD	psi-mi:“MI:0915”(physical association)	0.400
CD300LF	CD300LD	psi-mi:“MI:0915”(physical association)	0.400
CD300LD	CD300LD	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (2): CD300LD (Proximity Label-MS), TFF1 (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, O95944, Q2TB54, G3X8R9, P0DMS9, Q2LA85, Q86YW5, Q8K558, Q5RDA5, Q5T2D2, Q6UXN2, Q9JKE2, A1KXC4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

468 predictions. Top by Δscore:

Variant	Effect	Δscore
17:74592158:CTCA:C	donor_loss	1.0000
17:74592159:TCA:T	donor_loss	1.0000
17:74592160:CAC:C	donor_loss	1.0000
17:74592161:ACC:A	donor_loss	1.0000
17:74592162:C:CT	donor_loss	1.0000
17:74580111:GACCT:G	acceptor_loss	0.9900
17:74580113:CCTG:C	acceptor_loss	0.9900
17:74580114:C:CG	acceptor_loss	0.9900
17:74580115:T:G	acceptor_loss	0.9900
17:74582309:TGCC:T	acceptor_loss	0.9800
17:74582310:GCCTA:G	acceptor_loss	0.9800
17:74582312:C:G	acceptor_loss	0.9800
17:74592161:A:AC	donor_gain	0.9800
17:74592162:C:CC	donor_gain	0.9800
17:74580114:C:CC	acceptor_gain	0.9700
17:74582213:CCTA:C	donor_loss	0.9700
17:74582214:CTA:C	donor_loss	0.9700
17:74582215:TACCT:T	donor_loss	0.9700
17:74582216:A:C	donor_loss	0.9700
17:74582217:C:T	donor_loss	0.9700
17:74580002:TCAAG:T	donor_gain	0.9600
17:74582312:C:CC	acceptor_gain	0.9600
17:74582321:C:CT	acceptor_loss	0.9600
17:74582211:CACCT:C	donor_loss	0.9400
17:74582212:ACCTA:A	donor_loss	0.9400
17:74582322:A:T	acceptor_loss	0.9400
17:74588505:TCTTA:T	donor_loss	0.9400
17:74588506:CTTAC:C	donor_loss	0.9400
17:74588507:TTAC:T	donor_loss	0.9400
17:74588508:TACC:T	donor_loss	0.9400

AlphaMissense

1244 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:74588620:G:C	F90L	0.750
17:74588620:G:T	F90L	0.750
17:74588622:A:G	F90L	0.750
17:74588740:C:A	K50N	0.663
17:74588740:C:G	K50N	0.663
17:74580050:G:C	S179R	0.621
17:74580050:G:T	S179R	0.621
17:74580052:T:G	S179R	0.621
17:74588737:C:A	W51C	0.621
17:74588737:C:G	W51C	0.621
17:74588755:C:A	W45C	0.596
17:74588755:C:G	W45C	0.596
17:74588716:C:A	W58C	0.583
17:74588716:C:G	W58C	0.583

dbSNP variants (sampled 300 via entrez): RS1000238531 (17:74589102 C>G), RS1000647705 (17:74578575 T>G), RS1000650393 (17:74585147 G>A,T), RS1000765123 (17:74584916 T>A), RS1001157815 (17:74578705 G>A), RS1001324339 (17:74594035 A>G), RS1001461045 (17:74579358 G>A), RS1001522897 (17:74583591 T>C), RS1001570989 (17:74594211 A>G,T), RS1001614679 (17:74579566 G>A), RS1001880833 (17:74579285 A>G), RS1001990592 (17:74584705 C>T), RS1001994810 (17:74583396 G>A,C), RS1002117141 (17:74589912 G>A,T), RS1002248816 (17:74589331 G>C)

Disease associations

OMIM: gene MIM:616301 | 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
GCST90000015_29	Parkinson’s disease motor subtype (tremor to postural instability/gait difficulty score ratio)	9.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0600011	Parkinson’s disease symptom measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation	1
Rotenone	decreases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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