FMN2

Chr 1AR

formin 2

NCBI Gene: 56776ENSG00000155816UniProt: Q9NZ56

This gene is a member of the formin homology protein family. The encoded protein is thought to have essential roles in organization of the actin cytoskeleton and in cell polarity. This protein mediates the formation of an actin mesh that positions the spindle during oogenesis and also regulates the formation of actin filaments in the nucleus. This protein also forms a perinuclear actin/focal-adhesion system that regulates the shape and position of the nucleus during cell migration. Mutations in this gene have been associated with infertility and also with an autosomal recessive form of intellectual disability (MRT47). Alternatively spliced transcript variants have been identified. [provided by RefSeq, Jul 2017]

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal recessive 47MIM #616193
AR
678
ClinVar variants
66
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— FMN2
⚡
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.
📋
ClinVar Variants
66 Pathogenic / Likely Pathogenic· 178 VUS of 678 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.27LOEUF
pLI 0.998
Z-score 6.11
OE 0.16 (0.10–0.27)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.32Z-score
OE missense 0.97 (0.92–1.03)
856 obs / 882.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.16 (0.10–0.27)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.97 (0.92–1.03)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.32
0≤1.21.6
LoF obs/exp: 10 / 61.9Missense obs/exp: 856 / 882.6Syn Z: -4.80

ClinVar Variant Classifications

678 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic58
Likely Pathogenic8
VUS178
Likely Benign181
Benign28
Conflicting13
58
Pathogenic
8
Likely Pathogenic
178
VUS
181
Likely Benign
28
Benign
13
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
0
55
0
58
Likely Pathogenic
3
1
4
0
8
VUS
0
155
23
0
178
Likely Benign
2
20
15
144
181
Benign
0
7
4
17
28
Conflicting
—13
Total8183101161466

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

View in ClinVar →

Protein Context — Lollipop Plot

FMN2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

FMN2-related nonsyndromic intellectual disability

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
FORMIN 2; FMN2
MIM #606373 · *

Intellectual developmental disorder, autosomal recessive 47

MIM #616193

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Involvement of methylation-associated silencing of formin 2 in colorectal carcinogenesis.
Li DJ et al.·World J Gastroenterol
2018
Heterozygous FMN2 missense variant found in a family case of premature ovarian insufficiency.
Li J et al.·J Ovarian Res
2022Case report
Distinct pathways for genetic and epigenetic predisposition in familial and bilateral Wilms tumor.
Wegert J et al.·Genome Med
2025
Three CircRNAs Function as Potential Biomarkers for Colorectal Cancer.
Zhang J et al.·Clin Lab
2020
Methylation markers for anal cancer screening: A repeated cross-sectional analysis of people living with HIV, 2015-2016.
Vasavada A et al.·Int J Cancer
2024
Genetic determinants of trabecular and cortical volumetric bone mineral densities and bone microstructure.
Paternoster L et al.·PLoS Genet
2013Meta-analysis
Insights Into the Antigenic Repertoire of Unclassified Synaptic Antibodies.
Gilligan M et al.·Ann Clin Transl Neurol
2026
Reconstruction of kidney renal clear cell carcinoma evolution across pathological stages.
Pang S et al.·Sci Rep
2018
Genomic relevance of FGF14 and associated genes on the prognosis of pancreatic cancer.
Raja A et al.·PLoS One
2021
Genome-wide DNA methylation profiling identifies two novel genes in cervical neoplasia.
El-Zein M et al.·Int J Cancer
2020
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools