FERMT2

protein-coding

FERM domain containing kindlin 2, the group of FERM domain containing|Fermitins|Pleckstrin homology domain containing

Gene summary

Enables several functions, including phosphatidylinositol-3,4,5-trisphosphate binding activity; protein serine/threonine kinase binding activity; and type I transforming growth factor beta receptor binding activity. Involved in several processes, including cell surface receptor signaling pathway; positive regulation of cellular component biogenesis; and positive regulation of intracellular signal transduction. Acts upstream of or within cell adhesion and protein localization to cell junction. Located in several cellular components, including adherens junction; cytoplasmic side of plasma membrane; and focal adhesion. Biomarker of acute myeloid leukemia. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

PLEKHC1

MANE transcript

NM_006832.3

Inheritance

—

ClinVar variants

U:72B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.03

Max pathogenic AF

—

Genomic locus

chr14:52,857,268-52,952,435

External References & Databases

Ensembl (ENSG00000073712)

Transcript & Mutation Effects

hg38 • Region Span ~95.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FERMT2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 70

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006832.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	1 clinvar		3
missense			66 clinvar			66
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	72	1	0	73

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 64 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006832.3	RefSeq	NP_006823.1	14	MANE Select
ENST00000341590.8	Ensembl	ENSP00000340391.3	14	MANE Select
NM_001134999.2	RefSeq	NP_001128471.1	15	Standard
NM_001135000.2	RefSeq	NP_001128472.1	14	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
fermt2	Danio rerio	Structure: cardiac muscle cell Quality: mislocalised abnormal

Gene / Model

Organism

Observed Phenotype

fermt2

Danio rerio

Structure: cardiac muscle cell

Quality: mislocalised

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

miR-targeted genes in epithelium - TarBase
miR-targeted genes in lymphocytes - TarBase
Cell-extracellular matrix interactions
Cell junction organization
Cell-Cell communication

Biological Process

cell-matrix adhesion
transforming growth factor beta receptor signaling pathway
integrin-mediated signaling pathway
regulation of cell shape
Wnt signaling pathway

Molecular Function

protein binding
phosphatidylinositol-3,4,5-trisphosphate binding
actin filament binding

Cellular Component

stress fiber
nucleus
nucleoplasm
cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000343279
Coding exons: 15
Length: 95168
Individuals with no LoFs: 125712
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 125714
p: 0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.96	258	363	0.711	0.0000173	4566
Missense (PolyPhen)		90	148.52	0.606		1899
Synonymous	0.250	122	126	0.972	0.00000614	1229
Loss of Function	5.44	1	36.4	0.0274	0.00000164	470

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000035	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Scaffolding protein that enhances integrin activation mediated by TLN1 and/or TLN2, but activates integrins only weakly by itself. Binds to membranes enriched in phosphoinositides. Enhances integrin-mediated cell adhesion onto the extracellular matrix and cell spreading; this requires both its ability to interact with integrins and with phospholipid membranes. Required for the assembly of focal adhesions. Participates in the connection between extracellular matrix adhesion sites and the actin cytoskeleton and also in the orchestration of actin assembly and cell shape modulation. Recruits FBLIM1 to focal adhesions. Plays a role in the TGFB1 and integrin signaling pathways. Stabilizes active CTNNB1 and plays a role in the regulation of transcription mediated by CTNNB1 and TCF7L2/TCF4 and in Wnt signaling. {ECO:0000269|PubMed:12679033, ECO:0000269|PubMed:18458155, ECO:0000269|PubMed:21325030, ECO:0000269|PubMed:22030399, ECO:0000269|PubMed:22078565, ECO:0000269|PubMed:22699938}.;

Recessive Scores

pRec: 0.134

Intolerance Scores

LoFtool: 0.0760
RVIS EVS: -0.69
RVIS percentile EVS: 15.2

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): H
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

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