FERMT3

Chr 11

FERM domain containing kindlin 3

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

NCBI Gene: 83706 ENSG00000149781 UniProt: Q86UX7

The FERMT3 protein activates integrins in hematopoietic cells and is required for integrin-mediated platelet adhesion and leukocyte adhesion to endothelial cells. Mutations cause autosomal recessive leukocyte adhesion deficiency type III (LAD-III), which affects both immune function and hemostasis. The gene is not highly constrained against loss-of-function variants.

ResearchSummary from RefSeq, OMIM, UniProt

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]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtLeukocyte adhesion deficiency 3

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · leukocyte adhesion deficiency 3 · AR · ClinGen 2019

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.56

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

1.51Z-score

OE missense 0.79 (0.72–0.87)

332 obs / 418.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.35 (0.23–0.56)

0≤0.351.4

Missense OE?0.79 (0.72–0.87)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 13 / 36.8Missense obs/exp: 332 / 418.8Syn Z: -0.26

Background carrier burden — how many people carry a rare variant somewhere in FERMT3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 58

853 rare PASS variants

Rare truncating (LoF)

1 in 2,000

78 rare PASS variants

Rare synonymous (reference)

1 in 170

349 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FERMT3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 110	1 in 1,900
South Asian	~43k	1 in 65	1 in 3,100
Remaining (unassigned)	~30k	1 in 54	1 in 2,300
European (Finnish)	~27k	1 in 390	1 in 3,300
Admixed American	~22k	1 in 57	1 in 2,800
African / African American	~21k	1 in 53	≈ 1 in 4,600
East Asian	~20k	1 in 65	1 in 1,800
Ashkenazi Jewish	~13k	1 in 230	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 55	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 14 coding exons well covered in gnomAD exomes and genomes.? see exons ↓