FDCSP

Summary

FDCSP (follicular dendritic cell secreted protein, HGNC:19215) is a protein-coding gene on chromosome 4q13.3, encoding Follicular dendritic cell secreted peptide (Q8NFU4). Can bind to the surface of B-lymphoma cells, but not T-lymphoma cells, consistent with a function as a secreted mediator acting upon B-cells.

This gene encodes a small secreted protein that is expressed in follicular dendritic cells. This protein specifically binds to activated B cells, and functions as a regulator of antibody responses. It is also thought to contribute to tumor metastases by promoting cancer cell migration and invasion.

Source: NCBI Gene 260436 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 19 total
• MANE Select transcript: NM_152997

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19215
Approved symbol	FDCSP
Name	follicular dendritic cell secreted protein
Location	4q13.3
Locus type	gene with protein product
Status	Approved
Aliases	FDC-SP
Ensembl gene	ENSG00000181617
Ensembl biotype	protein_coding
OMIM	607241
Entrez	260436

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000317987

RefSeq mRNA: 1 — MANE Select: NM_152997 NM_152997

CCDS: CCDS3537

Canonical transcript exons

ENST00000317987 — 5 exons

Exon	Start	End
ENSE00001277427	70232994	70233026
ENSE00001277448	70234020	70234215
ENSE00001277456	70231195	70231251
ENSE00001347105	70235085	70235252
ENSE00001347123	70226124	70226182

Expression profiles

Bgee: expression breadth ubiquitous, 157 present calls, max score 99.48.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 11.6793 / max 7482.8513, expressed in 144 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
47909	11.2849	140
47908	0.3944	51

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
olfactory segment of nasal mucosa	UBERON:0005386	99.48	gold quality
vermiform appendix	UBERON:0001154	98.48	gold quality
tonsil	UBERON:0002372	98.41	gold quality
lymph node	UBERON:0000029	97.22	gold quality
ileal mucosa	UBERON:0000331	97.08	gold quality
saliva-secreting gland	UBERON:0001044	96.68	gold quality
minor salivary gland	UBERON:0001830	96.40	gold quality
parotid gland	UBERON:0001831	95.17	gold quality
trachea	UBERON:0003126	92.87	gold quality
mouth mucosa	UBERON:0003729	92.56	gold quality
caecum	UBERON:0001153	91.59	gold quality
nasal cavity mucosa	UBERON:0001826	89.74	gold quality
superficial temporal artery	UBERON:0001614	86.20	gold quality
rectum	UBERON:0001052	86.17	gold quality
gingiva	UBERON:0001828	86.10	gold quality
superior surface of tongue	UBERON:0007371	84.55	gold quality
epithelium of mammary gland	UBERON:0003244	83.31	gold quality
mammary duct	UBERON:0001765	83.22	gold quality
oral cavity	UBERON:0000167	83.20	gold quality
epithelium of nasopharynx	UBERON:0001951	82.33	gold quality
gingival epithelium	UBERON:0001949	81.71	gold quality
lower esophagus mucosa	UBERON:0035834	79.06	gold quality
tongue	UBERON:0001723	78.32	gold quality
spleen	UBERON:0002106	77.58	gold quality
mammary gland	UBERON:0001911	73.66	gold quality
thoracic mammary gland	UBERON:0005200	73.60	gold quality
smooth muscle tissue	UBERON:0001135	72.93	gold quality
small intestine Peyer’s patch	UBERON:0003454	71.51	gold quality
mucosa of transverse colon	UBERON:0004991	70.53	gold quality
mucosa of sigmoid colon	UBERON:0004993	70.24	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-75688	yes	3085.83
E-CURD-7	yes	1295.44
E-ENAD-21	yes	1295.44
E-CURD-53	yes	891.70
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

9 targeting FDCSP, 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-3658	99.96	73.87	4379
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-6833-5P	99.50	68.93	1161
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-6830-5P	99.01	68.73	1884
HSA-MIR-676-5P	98.49	68.87	1492
HSA-MIR-561-5P	98.25	68.13	1365
HSA-MIR-4275	97.96	68.42	1549
HSA-MIR-125A-3P	97.04	66.92	902

Literature-anchored findings (GeneRIF, showing 9)

• FDC-SP has a very restricted tissue distribution, expressed by activated FDCs from tonsils and TNF-alpha-activated FDC-like cell lines, but not by B cell lines, primary germinal center B cells, or anti-CD40 plus IL-4-activated B cells. (PMID:12193705)
• Since only normal tissue was examined, these findings suggest that FDC-SP plays an important but previously unsuspected role within oral connective tissue. (PMID:16259954)
• These results provide the first evidence for immunomodulatory activities of FDC-SP and implicate this molecule as a regulator of B cell responses. (PMID:17548624)
• The role of C4orf7 in ovarian cancer cell morphology, motility and invasion was demonstrated. (PMID:20811673)
• FDC-SP overexpression inhibits osteogenic differentiation of hPDLCs. study contributes to a better understanding of biological functions governing FDC-SP-induced hPDLC differentiation. (PMID:24138099)
• Our findings demonstrate that transfection with FDC-SP has negligible adverse effect on proliferation of hPDLCs and imply the biological function of FDC-SP as a fibroblastic phenotype stabilizer (PMID:24357406)
• FDC-SP may be involved in IgA production in the tonsils of Immunoglobulin A nephropathy patients. (PMID:25953661)
• LPS-induced upregulation of FDC-SP expression in human periodontal ligament cells may enhance osteoclastogenesis in periodontal disease. (PMID:26577469)
• These studies show that TNF-alpha stimulates human FDC-SP gene transcription by targeting YY1, GATA, C/EBP2 and C/EBP3 in the FDC-SP gene promoter. (PMID:29356241)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Fdcsp	ENSMUSG00000105888
rattus_norvegicus	Fdcsp	ENSRNOG00000030258

Protein

Protein identifiers

Follicular dendritic cell secreted peptide — Q8NFU4 (reviewed: Q8NFU4)

All UniProt accessions (2): Q540F3, Q8NFU4

UniProt curated annotations — full annotation on UniProt →

Function. Can bind to the surface of B-lymphoma cells, but not T-lymphoma cells, consistent with a function as a secreted mediator acting upon B-cells.

Subcellular location. Secreted.

Tissue specificity. Abundantly expressed in tonsil, lymph node, and trachea; strong expression in prostate; lower expression in thyroid, stomach, and colon.

Post-translational modifications. O-glycosylated with core 1 or possibly core 8 glycans.

RefSeq proteins (1): NP_694542* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029187	FDC-SP	Family

Pfam: PF15215

UniProt features (3 total): signal peptide 1, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NFU4-F1	63.42	0.13

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 30 (showing top): RACCACAR_AML_Q6, chr4q13, AML_Q6, RICKMAN_HEAD_AND_NECK_CANCER_A, SABATES_COLORECTAL_ADENOMA_DN, OSF2_Q6, MIR4275, MIR6833_5P, CHIANG_LIVER_CANCER_SUBCLASS_PROLIFERATION_UP, BLANCO_MELO_COVID19_SARS_COV_2_POS_PATIENT_LUNG_TISSUE_UP, GSE15659_NAIVE_CD4_TCELL_VS_RESTING_TREG_UP, GSE15659_CD45RA_NEG_CD4_TCELL_VS_RESTING_TREG_UP, GSE15659_NONSUPPRESSIVE_TCELL_VS_ACTIVATED_TREG_UP, DURANTE_ADULT_OLFACTORY_NEUROEPITHELIUM_RESPIRATORY_SECRETORY_CELLS, DURANTE_ADULT_OLFACTORY_NEUROEPITHELIUM_BOWMANS_GLAND

GO Biological Process (0):

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

GO Cellular Component (1): extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

284 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FDCSP	ODAM	A1E959	702
FDCSP	PRR27	Q6MZM9	570
FDCSP	AMTN	Q6UX39	539
FDCSP	KAAG1	Q9UBP8	530
FDCSP	CXCL2	P19875	491
FDCSP	STATH	P02808	480
FDCSP	C4orf36	Q96KX1	445
FDCSP	CD40LG	P29965	436
FDCSP	CXCL8	P10145	420
FDCSP	OR6T1	Q8NGN1	418
FDCSP	SPACA7	Q96KW9	379
FDCSP	IL4	P05112	352
FDCSP	VN1R2	Q8NFZ6	340
FDCSP	SRGN	P10124	324
FDCSP	EBNA1BP2	Q99848	297

IntAct

11 interactions, top by confidence:

A	B	Type	Score
FDCSP	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
ASPH	FDCSP	psi-mi:“MI:0915”(physical association)	0.560
FDCSP	MFF	psi-mi:“MI:0915”(physical association)	0.560
FDCSP	FHIT	psi-mi:“MI:0914”(association)	0.350
FDCSP	UBQLN2	psi-mi:“MI:0915”(physical association)	0.000
MFF	FDCSP	psi-mi:“MI:0915”(physical association)	0.000
ASPH	FDCSP	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (11): FDCSP (Two-hybrid), UBQLN2 (Two-hybrid), ASPH (Two-hybrid), PBRM1 (Affinity Capture-MS), FHIT (Affinity Capture-MS), RBMXL1 (Affinity Capture-MS), SLTM (Affinity Capture-MS), UTP11L (Affinity Capture-MS), RRP36 (Affinity Capture-MS), PRPF38A (Affinity Capture-MS), SCAF11 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2K6Z9, A0A1D0BN92, A0A411D538, A1YQ92, B3A0Q4, D5L5Q8, H2A0M0, K9N4Q4, O08546, O15946, O35979, O35985, O36359, P06796, P07498, P0DMD3, P0DMD4, P11841, P13432, P15450, P18897, P34468, P54684, P55796, P79139, P81058, P81059, P83055, P83474, P86735, Q01493, Q09283, Q17RF5, Q28441, Q28451, Q28794, Q29135, Q29137, Q61900, Q7T6X1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	13
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

568 predictions. Top by Δscore:

Variant	Effect	Δscore
4:70226181:AGG:A	donor_loss	1.0000
4:70226183:GTA:G	donor_loss	1.0000
4:70231181:A:AG	acceptor_gain	1.0000
4:70231182:C:G	acceptor_gain	1.0000
4:70231186:A:AG	acceptor_gain	1.0000
4:70231187:T:G	acceptor_gain	1.0000
4:70231193:A:AG	acceptor_gain	1.0000
4:70231194:G:GG	acceptor_gain	1.0000
4:70231248:CCCA:C	donor_gain	1.0000
4:70231249:CCA:C	donor_gain	1.0000
4:70231250:CA:C	donor_gain	1.0000
4:70231251:AG:A	donor_loss	1.0000
4:70231252:G:GG	donor_gain	1.0000
4:70231253:T:A	donor_loss	1.0000
4:70231254:AA:A	donor_loss	1.0000
4:70232989:TTTA:T	acceptor_loss	1.0000
4:70232990:TTA:T	acceptor_loss	1.0000
4:70232991:TAG:T	acceptor_loss	1.0000
4:70232992:A:AG	acceptor_gain	1.0000
4:70232993:G:GG	acceptor_gain	1.0000
4:70233022:GAAGT:G	donor_gain	1.0000
4:70233023:AAGT:A	donor_gain	1.0000
4:70233025:GT:G	donor_gain	1.0000
4:70233027:G:GG	donor_gain	1.0000
4:70226183:G:GG	donor_gain	0.9900
4:70231177:A:AG	acceptor_gain	0.9900
4:70231178:T:G	acceptor_gain	0.9900
4:70231190:TGCA:T	acceptor_loss	0.9900
4:70231191:GCAGA:G	acceptor_loss	0.9900
4:70231247:TCCCA:T	donor_gain	0.9900

AlphaMissense

550 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:70231232:C:A	A13E	0.953
4:70231223:C:A	A10D	0.950
4:70231220:C:A	T9K	0.938
4:70231220:C:G	T9R	0.924
4:70231235:T:A	V14E	0.919
4:70231243:G:C	G17R	0.911
4:70231222:G:C	A10P	0.903
4:70231226:T:A	I11N	0.880
4:70231231:G:C	A13P	0.871
4:70231238:C:A	A15D	0.865
4:70231244:G:A	G17D	0.851
4:70231241:T:A	V16D	0.844
4:70231211:T:A	L6H	0.835
4:70233024:A:C	S30R	0.806
4:70233026:T:A	S30R	0.806
4:70233026:T:G	S30R	0.806
4:70231237:G:C	A15P	0.800
4:70231229:T:G	L12W	0.777
4:70231211:T:G	L6R	0.775
4:70231214:T:G	L7R	0.773
4:70234118:G:C	W63C	0.742
4:70234118:G:T	W63C	0.742
4:70234023:A:C	S32R	0.741
4:70234025:T:A	S32R	0.741
4:70234025:T:G	S32R	0.741
4:70231214:T:A	L7Q	0.731
4:70234029:A:C	S34R	0.727
4:70234031:C:A	S34R	0.727
4:70234031:C:G	S34R	0.727
4:70231208:T:A	L5H	0.723

dbSNP variants (sampled 300 via entrez): RS1000097984 (4:70226551 G>A,T), RS1000211549 (4:70231235 T>C), RS1000474341 (4:70229383 C>A,T), RS1000547534 (4:70229687 T>C), RS1000574027 (4:70232834 T>C), RS1000771592 (4:70226493 C>T), RS1001309155 (4:70229577 T>C), RS1001363565 (4:70230471 T>A,C), RS1001777190 (4:70230115 C>A), RS1001809469 (4:70234724 T>C), RS1002315121 (4:70228193 T>C), RS1002923620 (4:70225040 A>G), RS1003045370 (4:70228825 T>G), RS1003480204 (4:70233369 T>A), RS1003552797 (4:70233695 G>A)

Disease associations

OMIM: gene MIM:607241 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
quercitrin	decreases expression	1
abrine	increases expression	1
Nickel	increases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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