CD300C

Summary

CD300C (CD300c molecule, HGNC:19320) is a protein-coding gene on chromosome 17q25.1, encoding CMRF35-like molecule 6 (Q08708).

The CMRF35 antigen, which was identified by reactivity with a monoclonal antibody, is present on monocytes, neutrophils, and some T and B lymphocytes (Jackson et al., 1992 [PubMed 1349532]).

Source: NCBI Gene 10871 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 54 total
• MANE Select transcript: NM_006678

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19320
Approved symbol	CD300C
Name	CD300c molecule
Location	17q25.1
Locus type	gene with protein product
Status	Approved
Aliases	CMRF35, LIR, CMRF-35A, CMRF35A, IGSF16
Ensembl gene	ENSG00000167850
Ensembl biotype	protein_coding
OMIM	606786
Entrez	10871

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 nonsense_mediated_decay

ENST00000330793, ENST00000718286

RefSeq mRNA: 1 — MANE Select: NM_006678 NM_006678

CCDS: CCDS11701

Canonical transcript exons

ENST00000330793 — 4 exons

Exon	Start	End
ENSE00001270942	74541073	74541736
ENSE00001270950	74545722	74546115
ENSE00004034624	74544609	74544947
ENSE00004034625	74542861	74542987

Expression profiles

Bgee: expression breadth ubiquitous, 150 present calls, max score 93.82.

FANTOM5 (CAGE): breadth broad, TPM avg 4.2590 / max 182.7254, expressed in 375 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
167949	3.1979	314
167948	0.3675	133
167951	0.2726	136
167950	0.2445	143
167947	0.1111	57
167952	0.0654	28

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	93.82	gold quality
mononuclear cell	CL:0000842	93.30	gold quality
leukocyte	CL:0000738	93.17	gold quality
granulocyte	CL:0000094	92.36	gold quality
blood	UBERON:0000178	81.75	gold quality
endometrium epithelium	UBERON:0004811	79.44	gold quality
spleen	UBERON:0002106	74.21	gold quality
upper lobe of left lung	UBERON:0008952	72.92	gold quality
cerebellar vermis	UBERON:0004720	71.83	gold quality
Brodmann (1909) area 10	UBERON:0013541	71.43	gold quality
frontal pole	UBERON:0002795	71.21	gold quality
vermiform appendix	UBERON:0001154	71.00	gold quality
paraflocculus	UBERON:0005351	70.77	gold quality
upper lobe of lung	UBERON:0008948	70.53	gold quality
middle frontal gyrus	UBERON:0002702	70.49	gold quality
right lung	UBERON:0002167	70.22	gold quality
caecum	UBERON:0001153	69.49	gold quality
bone marrow	UBERON:0002371	69.43	gold quality
right coronary artery	UBERON:0001625	67.98	gold quality
descending thoracic aorta	UBERON:0002345	65.96	gold quality
gall bladder	UBERON:0002110	65.95	gold quality
smooth muscle tissue	UBERON:0001135	65.72	gold quality
left coronary artery	UBERON:0001626	64.86	gold quality
coronary artery	UBERON:0001621	64.65	gold quality
omental fat pad	UBERON:0010414	64.65	gold quality
peritoneum	UBERON:0002358	64.63	gold quality
lymph node	UBERON:0000029	64.62	gold quality
bone marrow cell	CL:0002092	64.35	silver quality
adipose tissue of abdominal region	UBERON:0007808	64.15	gold quality
left adrenal gland	UBERON:0001234	64.07	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.93

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

27 targeting CD300C, 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-4481	100.00	66.42	1669
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-4284	99.36	65.25	1293
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-5589-3P	99.29	68.30	1443
HSA-MIR-642A-3P	99.23	67.67	1258
HSA-MIR-642B-3P	99.23	67.67	1258
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-4254	99.11	65.15	1315
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-4257	97.86	68.05	1190
HSA-MIR-146B-3P	97.83	65.29	782
HSA-MIR-665	97.60	65.64	1781
HSA-MIR-512-5P	97.47	66.48	591
HSA-MIR-616-3P	96.82	66.99	784
HSA-MIR-6508-3P	96.73	65.48	576
HSA-MIR-6857-3P	96.70	65.43	915
HSA-MIR-3690	96.44	65.18	737
HSA-MIR-3918	96.13	64.65	1300
HSA-MIR-2861	95.24	65.47	1056

Literature-anchored findings (GeneRIF, showing 9)

• CMRF35A and CMRF35H have roles in immunoglobulin signaling; CMRF35A induces cellular activation and effector function [review] (PMID:12456026)
• CD300a and CD300c play an important role in the cross-regulation of TNF-alpha and IFN-alpha secretion from pDCs; CD300a/c RNA and surface expression were downregulated after stimulation of pDCs with TLR7 and TLR9 ligands (PMID:18535206)
• CD300a and CD300c receptors are indistinguishable on the surface of natural killer (NK) cells. The tyrosine residue in the third ITIM motif, Tyr-267-Ala, is the most important residue for execution of the inhibitory signal. (PMID:20656921)
• differential expression on human TH1 and TH17 cell memory subsets (PMID:22046970)
• engagement of CD300C led to Fc receptor gamma-dependent activation of mast cells and monocytes (PMID:23372157)
• potential role in inflammatory responses (PMID:23571507)
• Results show that CD300c is exclusively expressed on CD56bright natural killer cells and differentially binds to phosphatidylethanolamine and phosphatidylserine. This expression is under the regulation of STAT5 and Il-4. (PMID:27040328)
• CD300c could be considered a biomarker and therapeutic target in patients with IgE-mediated allergic diseases (PMID:29906528)
• Administration of CD300c-Fc protein attenuates graft-vs.-host disease (GVHD) in mice. (PMID:30498497)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cd300c2	ENSMUSG00000044811
mus_musculus	Cd300c	ENSMUSG00000058728
rattus_norvegicus	Cd300cl1	ENSRNOG00000045888
rattus_norvegicus	Cd300cl1	ENSRNOG00000046121
rattus_norvegicus	Igsf7l1	ENSRNOG00000046216
rattus_norvegicus	Cd300c2l1	ENSRNOG00000048771
rattus_norvegicus	AABR07030773.1	ENSRNOG00000050974
rattus_norvegicus	Cd300a	ENSRNOG00000057058
rattus_norvegicus	AABR07030796.1	ENSRNOG00000059563

Paralogs (13): TREM2 (ENSG00000095970), TMIGD3 (ENSG00000121933), CD300LG (ENSG00000161649), TREML1 (ENSG00000161911), FCMR (ENSG00000162894), PIGR (ENSG00000162896), FCAMR (ENSG00000162897), CD300A (ENSG00000167851), CD300LB (ENSG00000178789), CD300LF (ENSG00000186074), CD300E (ENSG00000186407), CD300LD (ENSG00000204345), CD300H (ENSG00000284690)

Protein

Protein identifiers

CMRF35-like molecule 6 — Q08708 (reviewed: Q08708)

Alternative names: CD300 antigen-like family member C, CMRF35-A1, Immunoglobulin superfamily member 16

All UniProt accessions (1): Q08708

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cell membrane.

Tissue specificity. Present on the surface of monocytes, neutrophils, a proportion of peripheral blood T- and B-lymphocytes and lymphocytic cell lines.

Similarity. Belongs to the CD300 family.

RefSeq proteins (1): NP_006669* (*=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 (13 total): disulfide bond 2, topological domain 2, glycosylation site 2, signal peptide 1, chain 1, sequence variant 1, transmembrane region 1, domain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
9Z0M	X-RAY DIFFRACTION	1.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q08708-F1	74.06	0.42

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 (2): 43–110, 57–65

Glycosylation sites (2): 90, 99

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: 152 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GSE45365_NK_CELL_VS_CD8A_DC_UP, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, MODULE_45, MODULE_64, GOBP_REGULATION_OF_IMMUNE_RESPONSE, MODULE_75, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_UP, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, COATES_MACROPHAGE_M1_VS_M2_DN, GOBP_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_RESPONSE_TO_BIOTIC_STIMULUS, JOSEPH_RESPONSE_TO_SODIUM_BUTYRATE_DN

GO Biological Process (4): immune system process (GO:0002376), cellular defense response (GO:0006968), 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-1 pathways:

Category	Pathways
Adaptive Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
biological_process	1
defense response	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

1948 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD300C	GABARAP	O95166	989
CD300C	SQSTM1	Q13501	981
CD300C	GABARAPL2	P60520	979
CD300C	F5GZY7	F5GZY7	978
CD300C	MAP1LC3B	Q9GZQ8	972
CD300C	LILRB1	Q8NHL6	922
CD300C	NBR1	Q14596	921
CD300C	LILRA2	Q8N149	915
CD300C	MAP1A	P78559	912
CD300C	CALCOCO2	Q13137	910
CD300C	MAP1LC3A	Q9H492	906
CD300C	BNIP3	Q12983	905
CD300C	OPTN	Q96CV9	871
CD300C	FUNDC1	Q8IVP5	870
CD300C	BNIP3L	O60238	849

IntAct

37 interactions, top by confidence:

A	B	Type	Score
FCER1G	CD300C	psi-mi:“MI:0915”(physical association)	0.590
CD300LB	CD300C	psi-mi:“MI:0915”(physical association)	0.590
CD300C	CD300LB	psi-mi:“MI:0915”(physical association)	0.590
CD300C	FAM210B	psi-mi:“MI:0915”(physical association)	0.560
CD300C	TMEM167B	psi-mi:“MI:0915”(physical association)	0.560
LEPROTL1	CD300C	psi-mi:“MI:0915”(physical association)	0.560
CD300C	GPR151	psi-mi:“MI:0915”(physical association)	0.560
CD300C	UNC93A	psi-mi:“MI:0915”(physical association)	0.560
GPR42	CD300C	psi-mi:“MI:0915”(physical association)	0.560
CD300C	Cd300lb	psi-mi:“MI:0915”(physical association)	0.400
CD300C	CD300C	psi-mi:“MI:0915”(physical association)	0.400
TYROBP	CD300C	psi-mi:“MI:0915”(physical association)	0.400
CD300C	CD300LF	psi-mi:“MI:0915”(physical association)	0.400
CD300C	CD300E	psi-mi:“MI:0915”(physical association)	0.400
CD300A	CD300C	psi-mi:“MI:0915”(physical association)	0.400
CD300C	MEST	psi-mi:“MI:0915”(physical association)	0.370
MED20	CD300C	psi-mi:“MI:0915”(physical association)	0.370
CD300C	GOPC	psi-mi:“MI:0915”(physical association)	0.370
CD300C	ATP12A	psi-mi:“MI:0914”(association)	0.350
CD300C	SMPD2	psi-mi:“MI:0914”(association)	0.350
CD300C	FAM210B	psi-mi:“MI:0915”(physical association)	0.000
CD300C	TMEM167B	psi-mi:“MI:0915”(physical association)	0.000
CD300C	LEPROTL1	psi-mi:“MI:0915”(physical association)	0.000
CD300C	GPR151	psi-mi:“MI:0915”(physical association)	0.000
CD300C	GPR42	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (18): ATP12A (Affinity Capture-MS), FAM210A (Affinity Capture-MS), FAM210A (Affinity Capture-MS), ATP12A (Affinity Capture-MS), CD300C (Two-hybrid), CD300C (Two-hybrid), CD300C (Two-hybrid), CD300C (Two-hybrid), GPR151 (Two-hybrid), TMEM167B (Two-hybrid), ATP12A (Affinity Capture-MS), FAM210A (Affinity Capture-MS), SMPD2 (Affinity Capture-MS), MGST1 (Affinity Capture-MS), TNNC2 (Affinity Capture-MS)

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, Q5RDA5, Q5T2D2, Q6UXN2, Q9JKE2

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 18 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	5	43.6×	2e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	42
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

819 predictions. Top by Δscore:

Variant	Effect	Δscore
17:74541732:GGGAG:G	acceptor_gain	1.0000
17:74541737:C:CC	acceptor_gain	1.0000
17:74542983:CCCGG:C	acceptor_gain	1.0000
17:74542984:CCGG:C	acceptor_gain	1.0000
17:74542984:CCGGC:C	acceptor_gain	1.0000
17:74542985:CGG:C	acceptor_gain	1.0000
17:74542985:CGGC:C	acceptor_gain	1.0000
17:74542988:C:CC	acceptor_gain	1.0000
17:74541733:GGAG:G	acceptor_gain	0.9900
17:74541734:GAG:G	acceptor_gain	0.9900
17:74541735:AGC:A	acceptor_loss	0.9900
17:74541736:GCT:G	acceptor_loss	0.9900
17:74541737:C:T	acceptor_loss	0.9900
17:74542854:ACCTT:A	donor_loss	0.9900
17:74542855:CCTTA:C	donor_loss	0.9900
17:74542856:CTTAC:C	donor_loss	0.9900
17:74542857:TTA:T	donor_loss	0.9900
17:74542860:C:A	donor_loss	0.9900
17:74542986:GG:G	acceptor_gain	0.9900
17:74542987:GC:G	acceptor_loss	0.9900
17:74542988:C:A	acceptor_loss	0.9900
17:74542989:T:A	acceptor_loss	0.9900
17:74544626:TCA:T	donor_gain	0.9900
17:74544698:T:TA	donor_gain	0.9900
17:74541492:A:C	acceptor_gain	0.9800
17:74541735:AG:A	acceptor_gain	0.9800
17:74542859:A:AC	donor_gain	0.9800
17:74542859:AC:A	donor_gain	0.9800
17:74542860:C:CC	donor_gain	0.9800
17:74542860:CC:C	donor_gain	0.9800

AlphaMissense

1445 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:74544847:T:A	K54N	0.972
17:74544847:T:G	K54N	0.972
17:74544841:C:A	W56C	0.966
17:74544841:C:G	W56C	0.966
17:74544730:G:C	F93L	0.959
17:74544730:G:T	F93L	0.959
17:74544732:A:G	F93L	0.959
17:74544844:G:C	F55L	0.954
17:74544844:G:T	F55L	0.954
17:74544846:A:G	F55L	0.954
17:74544731:A:G	F93S	0.947
17:74544849:T:C	K54E	0.945
17:74544680:C:G	C110S	0.938
17:74544681:A:T	C110S	0.938
17:74544758:A:G	I84T	0.937
17:74544848:T:A	K54I	0.931
17:74544875:T:C	Y45C	0.931
17:74544731:A:C	F93C	0.930
17:74544687:A:C	Y108D	0.928
17:74544843:A:G	W56R	0.926
17:74544843:A:T	W56R	0.926
17:74541673:G:C	S197R	0.924
17:74541673:G:T	S197R	0.924
17:74541675:T:G	S197R	0.924
17:74544698:T:G	D104A	0.919
17:74544699:C:G	D104H	0.919
17:74544881:C:G	C43S	0.917
17:74544882:A:T	C43S	0.917
17:74544698:T:C	D104G	0.911
17:74544698:T:A	D104V	0.910

dbSNP variants (sampled 300 via entrez): RS1000239225 (17:74543889 G>A), RS1000343895 (17:74543553 G>A), RS1000539399 (17:74544938 G>A), RS1000569240 (17:74538588 G>T), RS1000573806 (17:74538468 C>T), RS1000820735 (17:74547046 G>C), RS1001002460 (17:74542088 A>G), RS1001544974 (17:74539780 G>A), RS1001557870 (17:74542361 C>T), RS1001560713 (17:74537894 C>G,T), RS1001895566 (17:74544407 C>G), RS1002307670 (17:74539550 A>G), RS1002337363 (17:74539361 A>G), RS1002371474 (17:74546676 C>G,T), RS1002545768 (17:74547172 A>C)

Disease associations

OMIM: gene MIM:606786 | 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
GCST006585_2455	Blood protein levels	8.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tretinoin	increases expression	2
bisphenol A	decreases methylation, affects cotreatment	1
sodium arsenite	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
tamibarotene	increases expression	1
CGP 52608	affects binding, increases reaction	1
Fulvestrant	affects cotreatment, decreases methylation	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	increases expression	1
Methapyrilene	increases methylation	1
Polychlorinated Biphenyls	affects expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	decreases 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.