FNDC8

Chr 17

fibronectin type III domain containing 8

Located in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

0
Active trials
7
Pathogenic / LP
75
ClinVar variants
1
Pubs (1 yr)
0.4
Missense Z
1.29
LOEUF
Clinical SummaryFNDC8
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
7 Pathogenic / Likely Pathogenic· 64 VUS of 75 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.29LOEUF
pLI 0.000
Z-score 0.92
OE 0.69 (0.391.29)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.43Z-score
OE missense 0.91 (0.801.04)
168 obs / 184.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.69 (0.391.29)
00.351.4
Missense OE0.91 (0.801.04)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 7 / 10.1Missense obs/exp: 168 / 184.2Syn Z: 0.08
DNGOF
DN
0.7132th %ile
GOF
0.7127th %ile
LOF
0.3939th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction 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

75 submitted variants in ClinVar

Classification Summary

Pathogenic7
VUS64
Likely Benign4
7
Pathogenic
64
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
0
0
0
0
VUS
0
56
8
0
64
Likely Benign
0
4
0
0
4
Benign
0
0
0
0
0
Total06015075

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

View in ClinVar →

FNDC8 · 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.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC