FERMT3

Chr 11AR

FERM domain containing kindlin 3

Also known as: KIND3, MIG-2, MIG2B, UNC112C, URP2, URP2SF

NCBI Gene: 83706ENSG00000149781UniProt: Q86UX7

Kindlins are a small family of proteins that mediate protein-protein interactions involved in integrin activation and thereby have a role in cell adhesion, migration, differentiation, and proliferation. The protein encoded by this gene has a key role in the regulation of hemostasis and thrombosis. This protein may also help maintain the membrane skeleton of erythrocytes. Mutations in this gene cause the autosomal recessive leukocyte adhesion deficiency syndrome-III (LAD-III). Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jan 2010]

Primary Disease Associations & Inheritance

Leukocyte adhesion deficiency, type IIIMIM #612840
AR
527
ClinVar variants
26
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— FERMT3
🧬
Gene-Disease Validity (ClinGen)
leukocyte adhesion deficiency 3 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
26 Pathogenic / Likely Pathogenic· 227 VUS of 527 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.56LOEUF
pLI 0.000
Z-score 3.64
OE 0.35 (0.23–0.56)
Moderately constrained

More LoF-intolerant than ~75% 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.
1.51Z-score
OE missense 0.79 (0.72–0.87)
332 obs / 418.8 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.0.35 (0.23–0.56)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.79 (0.72–0.87)
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.1.02
0≤1.21.6
LoF obs/exp: 13 / 36.8Missense obs/exp: 332 / 418.8Syn Z: -0.26

ClinVar Variant Classifications

527 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic6
VUS227
Likely Benign234
Benign29
Conflicting11
20
Pathogenic
6
Likely Pathogenic
227
VUS
234
Likely Benign
29
Benign
11
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
11
0
9
0
20
Likely Pathogenic
4
0
2
0
6
VUS
1
209
16
1
227
Likely Benign
0
7
88
139
234
Benign
0
2
19
8
29
Conflicting
—11
Total16218134148527

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

View in ClinVar →

Protein Context — Lollipop Plot

FERMT3 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Leukocyte adhesion deficiency, type III

MIM #612840

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Characterization of immune features and discovery of potential biomarkers for ankylosing spondylitis using deep plasma proteomics.
Xu X et al.·J Adv Res
2026
Independent prognostic biomarker FERMT3 associated with immune infiltration and immunotherapy response in glioma.
Zhuo S et al.·Ann Med
2023
Molecular Pathogenesis of Inherited Platelet Dysfunction.
Rodríguez-Alén A et al.·Biomolecules
2025Review
A Novel Deletion in FERMT3 Causes LAD-III in a Turkish Family.
Köker N et al.·J Clin Immunol
2023
Developing serum proteomics based prediction models of disease progression in ADPKD.
Aydogan Balaban HÖ et al.·Nat Commun
2025Functional
Integrative analysis identifies FERMT3 as a key regulator of metabolic reprogramming in keloid scarring and metabolic syndrome.
Lin Q et al.·Funct Integr Genomics
2025
Novel variants in FERMT3 and RASGRP2-Genetic linkage in Glanzmann-like bleeding disorders.
Manukjan G et al.·Pediatr Blood Cancer
2020Case report
Blockage of PD-L1 by FERMT3-mediated Wnt/β-catenin signalling regulates chemoresistance and immune evasion of colorectal cancer cells.
Tang Y et al.·Clin Exp Pharmacol Physiol
2022
LAD-1/variant syndrome is caused by mutations in FERMT3.
Kuijpers TW et al.·Blood
2009
Identification and validation of prognostic biomarkers in ccRCC: immune-stromal score and survival prediction.
Lyu F et al.·BMC Cancer
2025
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