DCSTAMP

Summary

DCSTAMP (dendrocyte expressed seven transmembrane protein, HGNC:18549) is a protein-coding gene on chromosome 8q22.3, encoding Dendritic cell-specific transmembrane protein (Q9H295). Probable cell surface receptor that plays several roles in cellular fusion, cell differentiation, bone and immune homeostasis.

This gene encodes a seven-pass transmembrane protein that is primarily expressed in dendritic cells. The encoded protein is involved in a range of immunological functions carried out by dendritic cells. This protein plays a role in osteoclastogenesis and myeloid differentiation. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 81501 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 68 total
• MANE Select transcript: NM_030788

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18549
Approved symbol	DCSTAMP
Name	dendrocyte expressed seven transmembrane protein
Location	8q22.3
Locus type	gene with protein product
Status	Approved
Aliases	DC-STAMP, FIND
Ensembl gene	ENSG00000164935
Ensembl biotype	protein_coding
OMIM	605933
Entrez	81501

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding_CDS_not_defined, 3 protein_coding

ENST00000297581, ENST00000517364, ENST00000517991, ENST00000518023, ENST00000518051, ENST00000519562, ENST00000520080, ENST00000622554

RefSeq mRNA: 2 — MANE Select: NM_030788 NM_001257317, NM_030788

CCDS: CCDS59111, CCDS6301

Canonical transcript exons

ENST00000297581 — 4 exons

Exon	Start	End
ENSE00001088777	104354877	104355185
ENSE00001088778	104339826	104339862
ENSE00001088779	104348541	104349581
ENSE00003490366	104356124	104356689

Expression profiles

Bgee: expression breadth ubiquitous, 141 present calls, max score 75.86.

FANTOM5 (CAGE): breadth broad, TPM avg 7.1210 / max 495.0581, expressed in 236 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
90177	6.8898	181
90176	0.2311	98

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	75.86	gold quality
buccal mucosa cell	CL:0002336	74.86	silver quality
amygdala	UBERON:0001876	72.93	gold quality
right lung	UBERON:0002167	71.89	gold quality
upper lobe of left lung	UBERON:0008952	68.51	gold quality
upper lobe of lung	UBERON:0008948	68.09	gold quality
islet of Langerhans	UBERON:0000006	65.46	gold quality
tibia	UBERON:0000979	62.25	gold quality
diaphragm	UBERON:0001103	62.13	gold quality
lung	UBERON:0002048	61.13	gold quality
epithelial cell of pancreas	CL:0000083	60.36	gold quality
right uterine tube	UBERON:0001302	60.14	gold quality
temporal lobe	UBERON:0001871	59.38	gold quality
Brodmann (1909) area 9	UBERON:0013540	57.74	gold quality
amniotic fluid	UBERON:0000173	57.37	silver quality
right lobe of liver	UBERON:0001114	57.26	gold quality
visceral pleura	UBERON:0002401	57.13	gold quality
decidua	UBERON:0002450	56.55	gold quality
pancreatic ductal cell	CL:0002079	56.54	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	55.87	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	55.85	gold quality
tibialis anterior	UBERON:0001385	55.74	silver quality
leukocyte	CL:0000738	55.64	gold quality
mononuclear cell	CL:0000842	55.63	gold quality
monocyte	CL:0000576	55.39	gold quality
hair follicle	UBERON:0002073	55.39	gold quality
right frontal lobe	UBERON:0002810	55.25	gold quality
granulocyte	CL:0000094	53.79	gold quality
lymph node	UBERON:0000029	53.55	gold quality
subcutaneous adipose tissue	UBERON:0002190	52.75	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.08

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, FOS, MITF, NFATC1, NFKB, SPI1, TAL1, TBX6

miRNA regulators (miRDB)

29 targeting DCSTAMP, 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-6077	99.99	68.04	2299
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-548G-3P	99.48	68.67	2159
HSA-MIR-4666A-5P	99.41	69.72	1887
HSA-MIR-5580-5P	99.38	66.96	1139
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-6088	99.29	68.45	1284
HSA-MIR-5584-3P	99.23	68.79	1351
HSA-MIR-6510-5P	99.14	66.59	1081
HSA-MIR-4695-5P	99.06	64.87	1151
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-4451	98.82	68.17	1455
HSA-MIR-760	98.81	66.65	1392
HSA-MIR-6754-5P	98.60	65.54	1627
HSA-MIR-6878-5P	98.49	67.91	2142
HSA-MIR-4536-5P	98.47	64.39	657
HSA-MIR-5087	98.01	69.09	965
HSA-MIR-6502-3P	97.86	65.43	569
HSA-MIR-4786-5P	97.45	67.89	924
HSA-MIR-6892-5P	97.27	68.60	847
HSA-MIR-4662A-3P	97.02	67.77	941
HSA-MIR-5002-3P	95.75	67.04	542
HSA-MIR-184	94.24	64.40	152
HSA-MIR-4304	90.01	61.07	99

Literature-anchored findings (GeneRIF, showing 17)

• The dendritic cell-specific transmembrane protein is a multimembrane-spanning protein preferentially expressed by human DC (hDC). (PMID:15601667)
• An interaction between OS9 and DC-STAMP was confirmed by yeast-2-hybrid analysis and cellular colocalization.ER-to-Golgi translocation of DC-STAMP following TLR stimulation in CHO cells was demonstrated, involving the DC-STAMP/OS9 interaction. The data indicate that OS9 is critically involved in ER-to-Golgi transport of DC-STAMP, and may be important in both myeloid differentiation and cell fusion. (PMID:18952287)
• 2 differentially expressed genes over-expressed in papillary thyroid cancers were identified as DC-STAMP and type I collagen A1 (PMID:19259350)
• DC-STAMP interacts with ER-resident transcription factor LUMAN which becomes activated during DC maturation. (PMID:20546900)
• genetic risk for Paget’s disease of bone is associated with variants close to CSF1, OPTN, TM7SF4, and TNFRSF11A genes (PMID:20839008)
• DC-STAMP is a potential osteoclast precursors biomarker in inflammatory arthritis. (PMID:21987375)
• DC-STAMP is an ITIM-bearing molecule. Based on the 4 distinct patterns of DCSTAMP on human PBMC, it has potential to serve as a susceptible biomarker of psoriasis (Ps) as well as severity marker of Psoriatic Arthritis (PsA). (PMID:21987375)
• Results show that T cells played a pivotal role in a new in vitro Langhans giant cells (LGCs) formation system, in which DC-STAMP was involved, and occurred via a molecular mechanism that involved CD40-CD40L interaction and IFN-gamma secretion. (PMID:22058328)
• DC-STAMP inhibition by RNA interference consequently suppressed fusion and bone resorption of human osteoclasts. (PMID:23525827)
• Rs62620995 in the TM7SF4 gene was found to have a marginal association with Paget’s disease of bone in the French-Canadian population. (PMID:24370779)
• The EP in TKA differed from EP in aseptically failed THA by lower CCL3 and DC-STAMP mRNA and protein expression. EP of all studied inflammatory and osteoclastogenic molecules were similar in knee and hip OA. (PMID:25151085)
• Our findings also suggest that next generation sequencing may help explore the pathogenesis and aid the diagnosis of Juvenile Paget’s disease. (PMID:25891874)
• TM7SF4 plays an essential role in regulating cell cycle progression in breast cancer. (PMID:26636523)
• TM7SF4 may be involved in the progression of lung cancer. (PMID:28849122)
• Our results suggest that the rare genetic variant of TM7SF4 gene, found in our French-Canadian cohort of patients with Paget’s disease of bone and which encodes the DC-STAMP protein, increase the number of nuclei per multinucleated cells and affect DC-STAMP expression during osteoclastogenesis in Paget’s disease of bone. (PMID:29145829)
• Genetic regulatory mechanisms in human osteoclasts suggest a role for the STMP1 and DCSTAMP genes in Paget’s disease of bone. (PMID:30705363)
• Upregulation of dendrocyte-expressed seven transmembrane protein is associated with unfavorable outcomes in differentiated thyroid cancer. (PMID:37058220)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Dcstamp	ENSMUSG00000022303
rattus_norvegicus	Dcstamp	ENSRNOG00000004704

Paralogs (3): OCSTAMP (ENSG00000149635), DCST2 (ENSG00000163354), DCST1 (ENSG00000163357)

Protein

Protein identifiers

Dendritic cell-specific transmembrane protein — Q9H295 (reviewed: Q9H295)

Alternative names: Dendrocyte-expressed seven transmembrane protein, IL-four-induced protein, Transmembrane 7 superfamily member 4

All UniProt accessions (1): Q9H295

UniProt curated annotations — full annotation on UniProt →

Function. Probable cell surface receptor that plays several roles in cellular fusion, cell differentiation, bone and immune homeostasis. Plays a role in TNFSF11-mediated osteoclastogenesis. Cooperates with OCSTAMP in modulating cell-cell fusion in both osteoclasts and foreign body giant cells (FBGCs). Participates in osteoclast bone resorption. Involved in inducing the expression of tartrate-resistant acid phosphatase in osteoclast precursors. Plays a role in haematopoietic stem cell differentiation of bone marrow cells toward the myeloid lineage. Inhibits the development of neutrophilic granulocytes. Plays also a role in the regulation of dendritic cell (DC) antigen presentation activity by controlling phagocytic activity. Involved in the maintenance of immune self-tolerance and avoidance of autoimmune reactions.

Subunit / interactions. Monomer. Homodimer. Isoform 1 interacts (via the C-terminus cytoplasmic tail) with OS9 isoform 1 (via the C-terminus tail); the interaction induces DCSTAMP redistribution to the endoplasmic reticulum-Golgi intermediate compartment. Isoform 1 interacts (via the C-terminus cytoplasmic tail) with OS9 isoform 2 (via the C-terminus tail). Interacts with CREB3.

Subcellular location. Cell membrane. Endoplasmic reticulum membrane. Endoplasmic reticulum-Golgi intermediate compartment membrane. Endosome.

Tissue specificity. Preferentially expressed by dendritic cells (DCs). Detected in both immature and mature DCs. Highly expressed in lymph nodes, lung, kidney and liver. Expressed at lower levels in pancreas, bone marrow, spleen, leukocytes, in freshly isolated peripheral blood mononuclear cells (PBMC) and B-cells. Not expressed in freshly isolated monocytes.

Post-translational modifications. Glycosylated.

Domain organisation. Several domains are necessary for interacting with OS9. The region in the cytoplasmic tail that is necessary for interaction with OS9, is also required for its transport.

Induction. Expression is down-regulated by dexamethasone and up-regulated by IL4/interleukin-4 in macrophages. Down-regulated in CD40L-activated dendritic cells.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H295-1	1	yes
Q9H295-2	2

RefSeq proteins (2): NP_001244246, NP_110415* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012858	DC_STAMP-like	Domain
IPR051856	CSR-E3_Ligase_Protein	Family

Pfam: PF07782

UniProt features (18 total): topological domain 7, transmembrane region 6, splice variant 2, chain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H295-F1	82.44	0.38

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8874211	CREB3 factors activate genes

MSigDB gene sets: 168 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR, GOBP_DENDRITIC_CELL_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_RESPONSE_TO_INTERLEUKIN_4, GOBP_RESPONSE_TO_PEPTIDE, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GOBP_MEMBRANE_FUSION, GOBP_GROWTH, GOCC_CELL_SURFACE, GOBP_MYELOID_LEUKOCYTE_DIFFERENTIATION, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_REGULATION_OF_LEUKOCYTE_DIFFERENTIATION, GOBP_REGULATION_OF_HEMOPOIESIS, RUTELLA_RESPONSE_TO_CSF2RB_AND_IL4_UP

GO Biological Process (13): negative regulation of cell growth (GO:0030308), osteoclast differentiation (GO:0030316), positive regulation of macrophage fusion (GO:0034241), cellular response to macrophage colony-stimulating factor stimulus (GO:0036006), myeloid dendritic cell differentiation (GO:0043011), positive regulation of monocyte differentiation (GO:0045657), positive regulation of bone resorption (GO:0045780), membrane fusion (GO:0061025), cellular response to interleukin-4 (GO:0071353), cellular response to tumor necrosis factor (GO:0071356), osteoclast fusion (GO:0072675), immune system process (GO:0002376), cell differentiation (GO:0030154)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (8): endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), cell surface (GO:0009986), endosome membrane (GO:0010008), membrane (GO:0016020), endoplasmic reticulum-Golgi intermediate compartment membrane (GO:0033116), endosome (GO:0005768), endoplasmic reticulum (GO:0005783)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Unfolded Protein Response (UPR)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular response to cytokine stimulus	3
myeloid leukocyte differentiation	2
cellular anatomical structure	2
bounding membrane of organelle	2
endomembrane system	2
regulation of cell growth	1
cell growth	1
negative regulation of growth	1
negative regulation of cellular process	1
macrophage fusion	1
regulation of macrophage fusion	1
positive regulation of syncytium formation by plasma membrane fusion	1
response to macrophage colony-stimulating factor	1
myeloid dendritic cell activation	1
dendritic cell differentiation	1
positive regulation of myeloid leukocyte differentiation	1
monocyte differentiation	1
regulation of monocyte differentiation	1
regulation of bone resorption	1
bone resorption	1
positive regulation of multicellular organismal process	1
membrane organization	1
response to interleukin-4	1
response to tumor necrosis factor	1
syncytium formation by cell-cell fusion	1
multinuclear osteoclast differentiation	1
biological_process	1
cellular developmental process	1
binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
endosome	1
cytoplasmic vesicle membrane	1
endoplasmic reticulum-Golgi intermediate compartment	1
cytoplasmic vesicle	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

574 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DCSTAMP	OCSTAMP	Q9BR26	930
DCSTAMP	NFATC1	O95644	885
DCSTAMP	CTSK	P43235	881
DCSTAMP	ATP6V0D2	Q8N8Y2	830
DCSTAMP	TNFSF11	O14788	830
DCSTAMP	ACP5	P13686	822
DCSTAMP	OSCAR	Q8IYS5	815
DCSTAMP	MMP9	P14780	734
DCSTAMP	CALCR	P30988	711
DCSTAMP	FOS	P01100	691
DCSTAMP	OS9	Q13438	686
DCSTAMP	CSF1R	P07333	640
DCSTAMP	TRAF6	Q9Y4K3	610
DCSTAMP	CSF1	P09603	604
DCSTAMP	CD40LG	P29965	579

IntAct

7 interactions, top by confidence:

A	B	Type	Score
CREB3	DCSTAMP	psi-mi:“MI:0915”(physical association)	0.540
DCSTAMP	CREB3	psi-mi:“MI:0403”(colocalization)	0.540
DCSTAMP	CREB3	psi-mi:“MI:0915”(physical association)	0.540
CREB3	DCSTAMP	psi-mi:“MI:0403”(colocalization)	0.540

BioGRID (2): DCSTAMP (Affinity Capture-Western), OS9 (Two-hybrid)

ESM2 similar proteins: A0A140LIJ0, A1L3G9, A4IFL1, B9X187, O18968, O70491, P08033, P08034, P28230, P35212, P36380, P51915, P60572, Q02738, Q059Y8, Q0V8E7, Q1LXZ7, Q28FG4, Q29559, Q4QR83, Q5E9Z5, Q5FVF4, Q5FWS4, Q5JW98, Q5R7B4, Q5T197, Q5T1A1, Q60HF7, Q640M6, Q6GMB1, Q6WGK6, Q7SY10, Q7TNJ0, Q8BXV2, Q8C2L6, Q8C9E8, Q8CE93, Q8CEG0, Q8N5C1, Q8NDZ6

Diamond homologs: Q7TNJ0, Q9H295

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	57
Likely benign	7
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

722 predictions. Top by Δscore:

Variant	Effect	Δscore
8:104339858:AACCT:A	donor_gain	0.9900
8:104339859:ACCT:A	donor_gain	0.9900
8:104339860:CCT:C	donor_gain	0.9900
8:104339861:CT:C	donor_gain	0.9900
8:104339863:G:GG	donor_gain	0.9900
8:104348652:G:GT	donor_gain	0.9900
8:104356123:GATTC:G	acceptor_gain	0.9900
8:104339860:CCTG:C	donor_loss	0.9800
8:104339862:TG:T	donor_loss	0.9800
8:104339863:G:C	donor_loss	0.9800
8:104339864:T:G	donor_loss	0.9800
8:104339866:A:AG	donor_gain	0.9800
8:104339867:G:GG	donor_gain	0.9800
8:104355040:T:G	acceptor_gain	0.9800
8:104355040:T:TA	acceptor_gain	0.9800
8:104355043:A:AG	acceptor_gain	0.9800
8:104355185:GGTA:G	donor_loss	0.9800
8:104355186:G:A	donor_loss	0.9800
8:104355187:T:A	donor_loss	0.9800
8:104356119:TTCA:T	acceptor_loss	0.9800
8:104356120:TCA:T	acceptor_loss	0.9800
8:104356121:CA:C	acceptor_loss	0.9800
8:104356122:A:C	acceptor_loss	0.9800
8:104356123:G:GA	acceptor_loss	0.9800
8:104349377:G:GT	donor_gain	0.9700
8:104349422:G:GT	donor_gain	0.9700
8:104355008:A:AG	acceptor_gain	0.9700
8:104355009:G:GG	acceptor_gain	0.9700
8:104356122:A:AG	acceptor_gain	0.9700
8:104356123:G:GG	acceptor_gain	0.9700

AlphaMissense

3074 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:104349471:T:A	W307R	0.967
8:104349471:T:C	W307R	0.967
8:104355069:T:C	F408L	0.962
8:104355071:C:A	F408L	0.962
8:104355071:C:G	F408L	0.962
8:104349284:C:A	N244K	0.956
8:104349284:C:G	N244K	0.956
8:104355093:C:A	R416S	0.953
8:104348903:C:A	N117K	0.951
8:104348903:C:G	N117K	0.951
8:104349303:T:C	F251L	0.947
8:104349305:T:A	F251L	0.947
8:104349305:T:G	F251L	0.947
8:104355094:G:C	R416P	0.947
8:104349252:T:C	F234L	0.943
8:104349254:T:A	F234L	0.943
8:104349254:T:G	F234L	0.943
8:104349240:T:C	F230L	0.939
8:104349242:C:A	F230L	0.939
8:104349242:C:G	F230L	0.939
8:104349492:G:C	D314H	0.938
8:104355108:C:G	H421D	0.932
8:104349493:A:T	D314V	0.931
8:104349283:A:T	N244I	0.924
8:104349493:A:C	D314A	0.922
8:104349292:T:G	I247S	0.921
8:104348856:G:C	G102R	0.918
8:104349292:T:C	I247T	0.917
8:104356130:T:C	F449L	0.917
8:104356132:C:A	F449L	0.917

dbSNP variants (sampled 300 via entrez): RS1000220101 (8:104352319 A>G), RS1000255059 (8:104342702 C>A,G,T), RS1000522155 (8:104353696 G>C,T), RS1000593572 (8:104352580 C>A,T), RS1000995391 (8:104347577 T>C), RS1001095952 (8:104349107 G>A), RS1001107042 (8:104341610 C>T), RS1001178998 (8:104351141 A>G), RS1001383718 (8:104356376 G>A), RS1001559536 (8:104341392 G>A), RS1001637594 (8:104345042 C>T), RS1001970026 (8:104346474 T>G), RS1002001132 (8:104346245 A>C), RS1002107371 (8:104355466 G>A), RS1002405865 (8:104343388 C>T)

Disease associations

OMIM: gene MIM:605933 | 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
GCST001086_9	Paget’s disease	7.000000e-17

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	2
2,4,5,2’,4’,5’-hexachlorobiphenyl	increases expression	1
sodium arsenite	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
Am 580	increases expression	1
CGP 52608	affects binding, increases reaction	1
(+)-JQ1 compound	decreases expression	1
Rosiglitazone	increases expression	1
Amphotericin B	increases expression	1
Cadmium	decreases expression, increases abundance	1
Cholesterol	increases expression, increases reaction	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression	1
Methamphetamine	affects response to substance	1
Tretinoin	increases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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