FERMT3

FERM domain containing kindlin 3, the group of Fermitins|Pleckstrin homology domain containing|FERM domain containing

Basic information

Region (hg38): 11:64205925-64223896

Links

ENSG00000149781 ∙ NCBI:83706 ∙ OMIM:607901 ∙ HGNC:23151 ∙ Uniprot:Q86UX7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• leukocyte adhesion deficiency 3 (Strong), mode of inheritance: AR
• leukocyte adhesion deficiency 3 (Strong), mode of inheritance: AR
• leukocyte adhesion deficiency 3 (Supportive), mode of inheritance: AR
• leukocyte adhesion deficiency 3 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Leukocyte adhesion deficiency, type III	AR	Allergy/Immunology/Infectious; Hematologic	Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Individuals may have hematologic anomalies, and treatment (which may include RBC and platelet transfusions) may be indicated; BMT has been described	Allergy/Immunology/Infectious; Hematologic	9312170; 12595312; 17185466; 19234460; 19064721; 20357244; 21441448

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FERMT3 gene.

• Leukocyte adhesion deficiency 3 (420 variants)
• Inborn genetic diseases (32 variants)
• not provided (29 variants)
• not specified (13 variants)
• FERMT3-related condition (1 variants)
• Leukocyte adhesion deficiency (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FERMT3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5	107	8	120
missense			180	5	3	188
nonsense		1	2			3
start loss			1			1
frameshift	5		2			7
inframe indel			3			3
splice donor/acceptor (+/-2bp)	1	2				3
splice region			9	18	4	31
non coding			1	55	16	72
Total	6	3	194	167	27

Highest pathogenic variant AF is 0.00000657

Variants in FERMT3

This is a list of pathogenic ClinVar variants found in the FERMT3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-64207366-T-G		Leukocyte adhesion deficiency 3	Uncertain significance (Mar 12, 2022)
11-64207369-C-T		Leukocyte adhesion deficiency 3	Uncertain significance (Oct 03, 2019)
11-64207370-G-A		Leukocyte adhesion deficiency 3	Likely benign (Apr 18, 2023)
11-64207373-G-A		Leukocyte adhesion deficiency 3	Likely benign (May 23, 2023)
11-64207382-A-G		Leukocyte adhesion deficiency 3	Likely benign (Feb 14, 2023)
11-64207388-C-T		Leukocyte adhesion deficiency 3	Likely benign (Jul 06, 2022)
11-64207389-G-A		Leukocyte adhesion deficiency 3	Uncertain significance (Dec 18, 2019)
11-64207391-G-A		FERMT3-related disorder	Likely benign (May 23, 2019)
11-64207391-G-T		Leukocyte adhesion deficiency 3	Likely benign (Sep 07, 2022)
11-64207392-G-A		Leukocyte adhesion deficiency 3	Uncertain significance (Sep 01, 2021)
11-64207398-A-G		Leukocyte adhesion deficiency 3	Uncertain significance (Sep 27, 2022)
11-64207400-C-T		Leukocyte adhesion deficiency 3	Likely benign (Dec 16, 2023)
11-64207401-G-A		Leukocyte adhesion deficiency 3 • Inborn genetic diseases	Uncertain significance (Nov 29, 2021)
11-64207405-C-G		Leukocyte adhesion deficiency 3	Uncertain significance (Aug 23, 2022)
11-64207406-G-A		Leukocyte adhesion deficiency 3	Likely benign (Oct 05, 2022)
11-64207409-A-G		Leukocyte adhesion deficiency 3	Likely benign (Apr 30, 2023)
11-64207410-T-C		Leukocyte adhesion deficiency 3	Uncertain significance (Mar 01, 2022)
11-64207412-G-A		Leukocyte adhesion deficiency 3	Pathogenic (Mar 01, 2009)
11-64207416-C-G		Leukocyte adhesion deficiency 3 • Inborn genetic diseases	Uncertain significance (Jul 31, 2023)
11-64207420-G-A		Leukocyte adhesion deficiency 3 • Inborn genetic diseases	Uncertain significance (Oct 17, 2022)
11-64207420-G-T		Leukocyte adhesion deficiency 3	Uncertain significance (Jul 26, 2020)
11-64207438-A-G		Leukocyte adhesion deficiency 3	Uncertain significance (Mar 03, 2022)
11-64207439-G-A		Leukocyte adhesion deficiency 3	Likely benign (Oct 14, 2023)
11-64207450-C-T		Leukocyte adhesion deficiency 3	Uncertain significance (Dec 11, 2023)
11-64207451-C-T		Leukocyte adhesion deficiency 3	Likely benign (Jun 16, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FERMT3	protein_coding	protein_coding	ENST00000279227	14	17205

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000260	1.00	125696	0	52	125748	0.000207

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.51	332	419	0.793	0.0000302	4296
Missense in Polyphen		79	125.17	0.63115		1369
Synonymous	-0.262	188	183	1.02	0.0000130	1333
Loss of Function	3.64	13	36.8	0.353	0.00000207	370

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000235	0.000235
Ashkenazi Jewish	0.0000997	0.0000992
East Asian	0.000109	0.000109
Finnish	0.0000485	0.0000462
European (Non-Finnish)	0.000295	0.000290
Middle Eastern	0.000109	0.000109
South Asian	0.000229	0.000229
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a central role in cell adhesion in hematopoietic cells (PubMed:19234463, PubMed:26359933). Acts by activating the integrin beta-1-3 (ITGB1, ITGB2 and ITGB3) (By similarity). Required for integrin-mediated platelet adhesion and leukocyte adhesion to endothelial cells (PubMed:19234460). Required for activation of integrin beta-2 (ITGB2) in polymorphonuclear granulocytes (PMNs) (By similarity). {ECO:0000250|UniProtKB:Q8K1B8, ECO:0000269|PubMed:19234460, ECO:0000269|PubMed:19234463, ECO:0000269|PubMed:26359933}.
• Disease: DISEASE: Leukocyte adhesion deficiency 3 (LAD3) [MIM:612840]: A disorder characterized by recurrent bacterial infections without pus formation, leukocytosis and major bleeding disorders. {ECO:0000269|PubMed:18779414, ECO:0000269|PubMed:19064721, ECO:0000269|PubMed:19234460, ECO:0000269|PubMed:19234463, ECO:0000269|PubMed:19617577, ECO:0000269|PubMed:26359933}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Platelet activation - Homo sapiens (human);Platelet degranulation ;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;Hemostasis (Consensus)

Recessive Scores

• pRec: 0.126

Intolerance Scores

• loftool: 0.305
• rvis_EVS: -0.19
• rvis_percentile_EVS: 39.24

Haploinsufficiency Scores

• pHI: 0.171
• hipred: Y
• hipred_score: 0.652
• ghis: 0.551

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.813

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Fermt3
• Phenotype: digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype; immune system phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: fermt3b
• Affected structure: intersegmental vessel
• Phenotype tag: abnormal
• Phenotype quality: non-functional

Gene ontology

• Biological process: platelet degranulation;leukocyte cell-cell adhesion;integrin-mediated signaling pathway;positive regulation of cell migration;integrin activation;regulation of cell-cell adhesion mediated by integrin;substrate adhesion-dependent cell spreading;platelet aggregation
• Cellular component: podosome;extracellular region;membrane;cell junction;platelet alpha granule lumen;cell projection;extracellular exosome
• Molecular function: integrin binding