FSTL5 encodes a protein that binds calcium ions and regulates BMP signaling pathway activity in the extracellular region, participating in cell differentiation processes. The gene is highly constrained against loss-of-function variants (pLI ~1.0, LOEUF 0.63), but no definitive human disease associations have been established to date.

Summary from RefSeq
Research Assistant →
0
Active trials
6
Pubs (1 yr)
41
P/LP submissions
0%
P/LP missense
0.63
LOEUF
DN
Mechanism· predicted
Clinical SummaryFSTL5
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
41 unique Pathogenic / Likely Pathogenic· 140 VUS of 216 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.63LOEUF
pLI 0.000
Z-score 3.42
OE 0.42 (0.290.63)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.05Z-score
OE missense 0.99 (0.921.08)
426 obs / 428.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.42 (0.290.63)
00.351.4
Missense OE0.99 (0.921.08)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 17 / 40.5Missense obs/exp: 426 / 428.7Syn Z: -0.25
DN
0.6453th %ile
GOF
0.5857th %ile
LOF
0.3647th %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

216 submitted variants in ClinVar

Classification Summary

Pathogenic39
Likely Pathogenic2
VUS140
Likely Benign4
39
Pathogenic
2
Likely Pathogenic
140
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
39
0
39
Likely Pathogenic
0
0
2
0
2
VUS
0
119
21
0
140
Likely Benign
0
0
4
0
4
Benign
0
0
0
0
0
Total0119660185

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

View in ClinVar →

Protein Context — Lollipop Plot

FSTL5 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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