FERMT3 (FERM domain containing kindlin 3)

Gene

• Entrez ID: 83706
• Gene name: FERM domain containing kindlin 3
• Gene symbol: FERMT3
• Synonyms (NCBI Gene): KIND3, MIG-2, MIG2B, UNC112C, URP2, URP2SF
• Chromosome: 11
• Chromosome location: 11q13.1
• Summary: 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 t

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs121918295	C>T	Pathogenic	Coding sequence variant, stop gained
rs121918296	G>A	Pathogenic	Coding sequence variant, stop gained, genic upstream transcript variant, upstream transcript variant
rs121918297	C>T	Pathogenic	Coding sequence variant, stop gained
rs121918298	G>A	Pathogenic	Coding sequence variant, stop gained
rs142774418	C>A,T	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant
rs148021416	G>A,C	Conflicting-interpretations-of-pathogenicity	Synonymous variant, missense variant, coding sequence variant
rs149000560	G>A	Benign, conflicting-interpretations-of-pathogenicity	Upstream transcript variant, missense variant, genic upstream transcript variant, coding sequence variant
rs775138431	T>-	Pathogenic	Coding sequence variant, frameshift variant
rs1286499329	A>C,G	Pathogenic	Splice acceptor variant
rs1591028090	AA>-	Pathogenic	Coding sequence variant, frameshift variant
rs1591037806	->T	Pathogenic	Coding sequence variant, frameshift variant
rs1591038507	T>C	Pathogenic	Splice donor variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT733512	hsa-miR-4792	Luciferase reporter assay, Western blotting, qRT-PCR	32183929
MIRT994876	hsa-miR-3689a-3p	CLIP-seq
MIRT994877	hsa-miR-3689c	CLIP-seq
MIRT994878	hsa-miR-4504	CLIP-seq
MIRT994879	hsa-miR-4687-3p	CLIP-seq
MIRT994880	hsa-miR-542-3p	CLIP-seq
MIRT2229085	hsa-miR-1324	CLIP-seq
MIRT2229086	hsa-miR-3157-5p	CLIP-seq
MIRT2229087	hsa-miR-4691-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0002102	Component	Podosome	IEA
GO:0002102	Component	Podosome	ISS
GO:0005178	Function	Integrin binding	IBA
GO:0005178	Function	Integrin binding	IEA
GO:0005178	Function	Integrin binding	ISS
GO:0005515	Function	Protein binding	IPI	32296183
GO:0005576	Component	Extracellular region	TAS
GO:0007155	Process	Cell adhesion	IEA
GO:0007159	Process	Leukocyte cell-cell adhesion	IBA
GO:0007159	Process	Leukocyte cell-cell adhesion	IEA
GO:0007159	Process	Leukocyte cell-cell adhesion	IMP	19234460
GO:0007160	Process	Cell-matrix adhesion	IBA
GO:0007229	Process	Integrin-mediated signaling pathway	IEA
GO:0007229	Process	Integrin-mediated signaling pathway	IMP	19234460
GO:0008289	Function	Lipid binding	EXP	27101375
GO:0016020	Component	Membrane	HDA	19946888
GO:0030055	Component	Cell-substrate junction	IBA
GO:0030335	Process	Positive regulation of cell migration	IDA	19234463
GO:0030335	Process	Positive regulation of cell migration	IEA
GO:0031093	Component	Platelet alpha granule lumen	TAS
GO:0033622	Process	Integrin activation	IBA
GO:0033622	Process	Integrin activation	IDA	19234463
GO:0033622	Process	Integrin activation	IEA
GO:0033622	Process	Integrin activation	IMP	19234460
GO:0033632	Process	Regulation of cell-cell adhesion mediated by integrin	IBA
GO:0033632	Process	Regulation of cell-cell adhesion mediated by integrin	IDA	19234463
GO:0033632	Process	Regulation of cell-cell adhesion mediated by integrin	IEA
GO:0034446	Process	Substrate adhesion-dependent cell spreading	IMP	19234460
GO:0042995	Component	Cell projection	IEA
GO:0070062	Component	Extracellular exosome	HDA	20458337
GO:0070161	Component	Anchoring junction	IEA
GO:0070527	Process	Platelet aggregation	HMP	23382103
GO:0070527	Process	Platelet aggregation	IBA
GO:0070527	Process	Platelet aggregation	IEA
GO:0070527	Process	Platelet aggregation	ISS

Other IDs

• MIM: 607901
• HGNC: 23151
• e!Ensembl: ENSG00000149781

Protein

• UniProt ID: Q86UX7
• Protein name: Fermitin family homolog 3 (Kindlin-3) (MIG2-like protein) (Unc-112-related protein 2)
• Protein 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 ad
• PDB: 2YS3, 6V97, 6V9G, 7C3M
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF18124	Kindlin_2_N	11 → 98	Kindlin-2 N-terminal domain	Domain
  PF00373	FERM_M	258 → 558	FERM central domain	Domain
  PF00169	PH	355 → 457	PH domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Highly expressed in lymph node. Expressed in thymus, spleen and leukocytes. Weakly expressed in placenta, small intestine, stomach, testis and lung. Overexpressed in B-cell malignancies. {ECO:0000269|PubMed:12697302, ECO:0000269|PubMed
• Sequence:

  MAGMKTASGDYIDSSWELRVFVGEEDPEAESVTLRVTGESHIGGVLLKIVEQINRKQDWS
  DHAIWWEQKRQWLLQTHWTLDKYGILADARLFFGPQHRPVILRLPNRRALRLRASFSQPL
  FQAVAAICRLLSIRHPEELSLLRAPEKKEKKKKEKEPEEELYDLSKVVLAGGVAPALFRG
  MPAHFSDSAQTEACYHMLSRPQPPPDPLLLQRLPRPSSLSDKTQLHSRWLDSSRCLMQQG
  IKAGDALWLRFKYYSFFDLDPKTDPVRLTQLYEQARWDLLLEEIDCTEEEMMVFAALQYH
  INKLSQSGEVGEPAGTDPGLDDLDVALSNLEVKLEGSAPTDVLDSLTTIPELKDHLRIFR
  IPRRPRKLTLKGYRQHWVVFKETTLSYYKSQDEAPGDPIQQLNLKGCEVVPDVNVSGQKF
  CIKLLVPSPEGMSEIYLRCQDEQQYARWMAGCRLASKGRTMADSSYTSEVQAILAFLSLQ
  RTGSGGPGNHPHGPDASAEGLNPYGLVAPRFQRKFKAKQLTPRILEAHQNVAQLSLAEAQ
  LRFIQAWQSLPDFGISYVMVRFKGSRKDEILGIANNRLIRIDLAVGDVVKTWRFSNMRQW
  NVNWDIRQVAIEFDEHINVAFSCVSASCRIVHEYIGGYIFLSTRERARGEELDEDLFLQL
  TGGHEAF

• Sequence length: 667

Pathways

KEGG:

Platelet activation

Reactome:

Platelet degranulation

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Leukocyte adhesion deficiency	Pathogenic	rs121918296	RCV004798713	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Leukocyte adhesion deficiency 3	Pathogenic; Likely pathogenic	rs2134845306, rs2134880586, rs2134903776, rs121918296, rs121918297, rs121918298, rs121918295, rs2496016889, rs2495977429, rs2496031806, rs2496049730, rs1946445537, rs775138431, rs1286499329, rs1591028090, rs1591037806, rs1591038507, rs760261349	RCV002002460 RCV002248304 RCV000002827 RCV000002828 RCV000002829 RCV000002830 RCV000002831 RCV002852944 RCV002970954 RCV003335907 RCV003606055 RCV003865916 RCV000023665 RCV000024239 RCV000797176 RCV000808521 RCV000801162 RCV001218117	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATTENTION DEFICIT HYPERACTIVITY DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BLOOD PLATELET DISORDERS	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL LEUKOCYTE ADHERENCE DEFICIENCY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DESBUQUOIS SYNDROME	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
FERMT3-related disorder	Likely benign; Conflicting classifications of pathogenicity; Uncertain significance; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMORRHAGE	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LEUKOCYTE ADHESION DEFICIENCY TYPE 1	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LEUKOCYTE ADHESION DEFICIENCY TYPE III	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LEUKOCYTE ADHESION DEFICIENCY, TYPE III	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lymphoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MAJOR DEPRESSIVE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OLIGODENDROGLIOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OSTEOPETROSIS	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
UTERINE FIBROID	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uveal melanoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Anemia	Anemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Arthritis Gouty	Gouty arthritis	Pubtator	39511617	Associate	★☆☆☆☆ Found in Text Mining only
Attention deficit hyperactivity disorder	Attention Deficit Hyperactivity Disorder	GWASCAT_DG	21784300		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Attention deficit hyperactivity disorder	Attention Deficit Hyperactivity Disorder	GWASDB_DG	21784300		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Autistic Disorder	Autism	BEFREE	29274201		★☆☆☆☆ Found in Text Mining only
Bernard Soulier Syndrome	Bernard-soulier syndrome	Pubtator	29242293	Associate	★☆☆☆☆ Found in Text Mining only
Blood Coagulation Disorders	Blood Coagulation Disorders	BEFREE	31329860, 31724816		★☆☆☆☆ Found in Text Mining only
Blood Platelet Disorders	Platelet-type bleeding disorder	CTD_human_DG	18278053		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Blood Platelet Disorders	Platelet disorder	Pubtator	29242293, 33391282	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Breast Carcinoma	Breast Carcinoma	BEFREE	25344860, 27715393		★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	18722108	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Renal Cell	Renal cell carcinoma	Pubtator	39871215	Associate	★☆☆☆☆ Found in Text Mining only
Carotid Stenosis	Carotid artery stenosis	Pubtator	36304068	Associate	★☆☆☆☆ Found in Text Mining only
Chondroma	Chordoma	Pubtator	18722108	Associate	★☆☆☆☆ Found in Text Mining only
Chondrosarcoma	Chondrosarcoma	Pubtator	18722108	Associate	★☆☆☆☆ Found in Text Mining only
Chronic Lymphocytic Leukemia	Lymphocytic Leukemia	BEFREE	26658839		★☆☆☆☆ Found in Text Mining only
Congenital leukocyte adherence deficiency	Congenital Leukocyte Adherence Deficiency	BEFREE	19617577, 19854292, 20216991, 21441448, 21536861, 22431571, 22564402, 22983444, 25344860, 25854317, 27749372		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital Osteopetrosis	Congenital Osteopetrosis	CTD_human_DG	18278053		★☆☆☆☆ Found in Text Mining only
Deep Vein Thrombosis	Thrombosis	BEFREE	31477636		★☆☆☆☆ Found in Text Mining only
Fibroid Tumor	Leiomyoma	BEFREE	14745725		★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	BEFREE	28778805		★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	Pubtator	37795794	Stimulate	★☆☆☆☆ Found in Text Mining only
Glioblastoma Multiforme	Glioblastoma	BEFREE	28778805		★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	BEFREE	28778805		★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	Pubtator	37795794	Associate	★☆☆☆☆ Found in Text Mining only
Hemorrhage	Hemorrhage	Pubtator	19234460, 20378539, 22564402, 23437269, 29242293, 31329860	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Immunologic Deficiency Syndromes	Immunologic Deficiency Syndromes	BEFREE	22431571		★☆☆☆☆ Found in Text Mining only
leiomyosarcoma	Leiomyosarcoma	BEFREE	14745725		★☆☆☆☆ Found in Text Mining only
Leukemia Myeloid Acute	Myeloid leukemia	Pubtator	32183929	Associate	★☆☆☆☆ Found in Text Mining only
Leukocyte adhesion deficiency type 1	Leukocyte adhesion deficiency	Pubtator	19064721, 19234463, 22139635, 40263987	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Leukocyte adhesion deficiency type 1	Leukocyte adhesion deficiency	BEFREE	22139635, 30412664		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Leukocyte adhesion deficiency type 1	Leukocyte adhesion deficiency	GENOMICS_ENGLAND_DG	26729028		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Leukocyte Adhesion Deficiency Type III	Leukocyte adhesion deficiency	Pubtator	19064721, 19234460, 19234463, 20357244, 21536861, 22139635, 22564402, 22983444, 23595985, 24958846, 31329860, 33391282, 40263987	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Leukocyte Adhesion Deficiency Type III	Leukocyte adhesion deficiency	Pubtator	23437269	Inhibit	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Leukocyte adhesion deficiency type III	Leukocyte adhesion deficiency	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Leukocyte Adhesion Deficiency, Type III	Leukocyte adhesion deficiency	CLINGEN_DG	16876785, 18278053, 19064721, 19234460, 19234461, 19234463, 21441448, 22139635		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Leukocyte Adhesion Deficiency, Type III	Leukocyte adhesion deficiency	GENOMICS_ENGLAND_DG	18709451, 20216991, 26729028		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Leukocyte Adhesion Deficiency, Type III	Leukocyte adhesion deficiency	UNIPROT_DG	18779414, 19064721, 19234460, 19234463, 19617577, 26359933		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Leukocyte Adhesion Deficiency, Type III	Leukocyte adhesion deficiency	BEFREE	19064721, 24958846, 31724816		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Leukocyte Adhesion Deficiency, Type III	Leukocyte adhesion deficiency	ORPHANET_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Leukocyte Adhesion Deficiency, Type III	Leukocyte adhesion deficiency	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Leukocyte Adhesion Deficiency, Type III	Leukocyte adhesion deficiency	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Liver carcinoma	Liver carcinoma	BEFREE	30471857		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	25344860, 27715393		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	25344860, 27715393		★☆☆☆☆ Found in Text Mining only
Mammary Neoplasms	Mammary Neoplasms	BEFREE	30477537		★☆☆☆☆ Found in Text Mining only
melanoma	Melanoma	BEFREE	25344860, 27715393		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Melanoma	Pubtator	35048636	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma Cutaneous Malignant	Melanoma	Pubtator	35048636	Associate	★☆☆☆☆ Found in Text Mining only
Multiple Myeloma	Multiple myeloma	BEFREE	26658839		★☆☆☆☆ Found in Text Mining only
Myocardial Infarction	Myocardial Infarction	BEFREE	31817594		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	25344860, 26677948, 30477537		★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	Pubtator	32928872	Associate	★☆☆☆☆ Found in Text Mining only
Osteoarthritis	Osteoarthritis	Pubtator	23237804	Associate	★☆☆☆☆ Found in Text Mining only
Osteopetrosis	Osteopetrosis	CTD_human_DG	18278053		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Osteopetrosis	Osteopetrosis	Pubtator	20378539	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Osteopetrosis	Osteopetrosis	BEFREE	28095295		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Osteopetrosis Autosomal Dominant Type 2	Osteopetrosis	CTD_human_DG	18278053		★☆☆☆☆ Found in Text Mining only
Osteosarcoma	Osteosarcoma	BEFREE	28223823		★☆☆☆☆ Found in Text Mining only
Osteosarcoma	Osteosarcoma	Pubtator	29760609	Associate	★☆☆☆☆ Found in Text Mining only
Poikiloderma of Kindler	Poikiloderma Of Kindler	BEFREE	19854292		★☆☆☆☆ Found in Text Mining only
ST segment elevation myocardial infarction	ST Segment Elevation Myocardial Infarction	BEFREE	31817594		★☆☆☆☆ Found in Text Mining only
Thrombasthenia	Thrombasthenia	BEFREE	23207660		★☆☆☆☆ Found in Text Mining only
Thrombosis	Thrombosis	Pubtator	29242293	Associate	★☆☆☆☆ Found in Text Mining only
Uterine Fibroids	Uterine Fibroids	BEFREE	14745725		★☆☆☆☆ Found in Text Mining only