FDCSP

Chr 4

follicular dendritic cell secreted protein

Also known as: C4orf7, FDC-SP

NCBI Gene: 260436 ENSG00000181617 UniProt: Q8NFU4 OMIM: 607241

This gene encodes a small secreted protein that specifically binds to activated B cells and regulates antibody responses. Mutations in FDCSP are associated with immunodeficiency and developmental disorders, though the specific phenotypic spectrum is still being characterized. The gene shows low constraint against loss-of-function variants, and inheritance patterns for associated disorders remain to be fully established.

OMIM ResearchSummary from RefSeq, UniProt

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. [provided by RefSeq, Dec 2011]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.40

Clinical Summary— FDCSP

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Population Constraint (gnomAD)

Low constraint (pLI 0.08) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

13 VUS of 18 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.40LOEUF

pLI 0.082

Z-score 1.05

OE 0.46 (0.18–1.40)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.09Z-score

OE missense 1.04 (0.82–1.32)

48 obs / 46.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.46 (0.18–1.40)

0≤0.351.4

Missense OE?1.04 (0.82–1.32)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 2 / 4.4Missense obs/exp: 48 / 46.3Syn Z: 0.12

This gene — mechanism propensity

0.97top 5%

GOF

0.5953th %ile

LOF

0.04100th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

18 submitted variants in ClinVar

ClinVar

Classification Summary

VUS13

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	13	13
Likely Benign	1	1
Benign	0	0
Total	14	14

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

23 pathogenic / likely-pathogenic (of 33) ClinVar copy-number / structural variants overlap FDCSP — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →