INF2

Chr 14

inverted formin 2

Also known as: C14orf151, C14orf173, CMTDIE, FSGS5, pp9484

NCBI Gene: 64423ENSG00000203485UniProt: Q27J81

This gene represents a member of the formin family of proteins. It is considered a diaphanous formin due to the presence of a diaphanous inhibitory domain located at the N-terminus of the encoded protein. Studies of a similar mouse protein indicate that the protein encoded by this locus may function in polymerization and depolymerization of actin filaments. Mutations at this locus have been associated with focal segmental glomerulosclerosis 5.[provided by RefSeq, Aug 2010]

Primary Disease Associations & Inheritance

UniProtFocal segmental glomerulosclerosis 5
UniProtCharcot-Marie-Tooth disease, dominant intermediate E
572
ClinVar variants
11
Pathogenic / LP
0.97
pLI score· haploinsufficient
0
Active trials
Clinical Summary— INF2
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Gene-Disease Validity (ClinGen)
Charcot-Marie-Tooth disease dominant intermediate E · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
11 Pathogenic / Likely Pathogenic· 262 VUS of 572 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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.
0.31LOEUF
pLI 0.973
Z-score 5.64
OE 0.18 (0.11–0.31)
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.
2.31Z-score
OE missense 0.76 (0.71–0.82)
581 obs / 760.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.18 (0.11–0.31)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.76 (0.71–0.82)
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.1.03
0≤1.21.6
LoF obs/exp: 10 / 55.3Missense obs/exp: 581 / 760.0Syn Z: -0.46

ClinVar Variant Classifications

572 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic7
VUS262
Likely Benign262
Benign15
Conflicting22
4
Pathogenic
7
Likely Pathogenic
262
VUS
262
Likely Benign
15
Benign
22
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
0
6
1
0
7
VUS
7
222
26
7
262
Likely Benign
0
21
91
150
262
Benign
0
5
3
7
15
Conflicting
—22
Total7254125164572

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

View in ClinVar →

Protein Context — Lollipop Plot

INF2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — INF2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Management of pediatric hemolytic uremic syndrome.
Gülhan B et al.·Turk J Pediatr
2024Review
Regulation of formin INF2 and its alteration in INF2-linked inherited disorders.
Labat-de-Hoz L et al.·Cell Mol Life Sci
2024Review
INF2 mutations cause kidney disease through a gain-of-function mechanism.
Subramanian B et al.·Sci Adv
2024Functional
Genetic Characterization of Kidney Failure of Unknown Etiology in Spain: Findings From the GENSEN Study.
Blasco M et al.·Am J Kidney Dis
2024
Cisplatin-induced disruption of mitochondrial divisome leads to enhanced cisplatin resistance in cholangiocarcinoma.
Lv GY et al.·J Hepatol
2025
Role of formin INF2 in human diseases.
Zhao Y et al.·Mol Biol Rep
2022Review
The formin INF2 in disease: progress from 10 years of research.
Labat-de-Hoz L et al.·Cell Mol Life Sci
2020Review
The various Charcot-Marie-Tooth diseases.
Vallat JM et al.·Curr Opin Neurol
2013Review
Characterization of cytoskeletal and structural effects of INF2 variants causing glomerulopathy and neuropathy.
Ueda H et al.·Sci Rep
2023
INF2-Related Charcot-Marie-Tooth Disease in a Japanese Cohort: Genetic and Clinical Insights.
Yano C et al.·Ann Clin Transl Neurol
2026Cohort
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