FNDC3B

Chr 3

fibronectin type III domain containing 3B

Also known as: FAD104, PRO4979, YVTM2421

NCBI Gene: 64778 ENSG00000075420 UniProt: Q53EP0 OMIM: 611909

Enables RNA binding activity. Predicted to act upstream of or within several processes, including negative regulation of osteoblast differentiation; substrate adhesion-dependent cell spreading; and type II pneumocyte differentiation. Predicted to be located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.04

Clinical Summary— FNDC3B

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

127 VUS of 174 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.04LOEUF

pLI 1.000

Z-score 7.74

OE 0.00 (0.00–0.04)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

1.87Z-score

OE missense 0.80 (0.74–0.86)

551 obs / 689.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.04)

0≤0.351.4

Missense OE?0.80 (0.74–0.86)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 0 / 69.8Missense obs/exp: 551 / 689.5Syn Z: -0.39

This gene — mechanism propensity

0.3594th %ile

GOF

0.3491th %ile

LOF

0.76top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.04

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

174 submitted variants in ClinVar

ClinVar

Classification Summary

VUS127

Likely Benign5

Benign9

127

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	127	0	0	127
Likely Benign	1	0	4	5
Benign	4	1	4	9
Total	132	1	8	141

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

View in ClinVar →

26 pathogenic / likely-pathogenic (of 32) ClinVar copy-number / structural variants overlap FNDC3B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →