FGD2

protein-coding

FYVE, RhoGEF and PH domain containing 2, the group of Pleckstrin homology domain containing|Zinc fingers FYVE-type|Dbl family Rho GEFs

Gene summary

The protein encoded by this gene belongs to a family of guanine nucleotide exchange factors (GEFs) which control cytoskeleton-dependent membrane rearrangements by activating the cell division cycle 42 (CDC42) protein. This gene is expressed in B lymphocytes, macrophages, and dendritic cells. The encoded protein may play a role in leukocyte signaling and vesicle trafficking in antigen-presenting cells in the immune system. [provided by RefSeq, Oct 2016]

MANE transcript

NM_173558.4

Inheritance

—

ClinVar variants

U:112B:12

Top phenotype

Prostate cancer

gnomAD constraint

pLI —, LoF o/e 0.55

Max pathogenic AF

—

Genomic locus

chr6:37,005,646-37,029,299

External References & Databases

Ensembl (ENSG00000146192)

Transcript & Mutation Effects

hg38 • Region Span ~23.7 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 FGD2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 111

not providedTotal: 10

Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_173558.4. 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			1 clinvar	1 clinvar	4 clinvar	6
missense			110 clinvar	3 clinvar	4 clinvar	117
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	112	4	8	124

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_173558.4	RefSeq	NP_775829.2	16	MANE Select
ENST00000274963.13	Ensembl	ENSP00000274963.8	16	MANE Select
ENST00000373535.6	Ensembl	ENSP00000362635.2	3	Standard
ENST00000718346.1	Ensembl	ENSP00000520783.1	16	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signaling by GPCR
Signal Transduction
Rho GTPase cycle
Signaling by Rho GTPases
NRAGE signals death through JNK

Biological Process

cytoskeleton organization
G protein-coupled receptor signaling pathway
regulation of cell shape
actin cytoskeleton organization
regulation of Rho protein signal transduction

Molecular Function

guanyl-nucleotide exchange factor activity
Rho guanyl-nucleotide exchange factor activity
protein binding
small GTPase binding
metal ion binding

Cellular Component

ruffle
nucleus
cytoplasm
Golgi apparatus
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000274963
Coding exons: 16
Length: 23425
Individuals with no LoFs: 125641
Homozygous LoFs: 0
Heterozygous LoFs: 106
Defined: 125747
p: 0.000422

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.705	371	411	0.902	0.0000262	4240
Missense (PolyPhen)		140	164.83	0.84934		1635
Synonymous	-0.756	181	169	1.07	0.0000107	1293
Loss of Function	2.46	19	34.6	0.549	0.00000165	379

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.00035	0.00035	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0037	0.0037	notable
Finnish	0.00024	0.00023	rare
European (Non-Finnish)	0.00012	0.00012	rare
South Asian	0.000071	0.000065	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Activates CDC42, a member of the Ras-like family of Rho- and Rac proteins, by exchanging bound GDP for free GTP. Activates JNK1 via CDC42 but not RAC1. Binds to phosphatidylinositol 4,5-bisphosphate, phosphatidylinositol 3,4,5- trisphosphate, phosphatidylinositol 5-monophosphate, phosphatidylinositol 4-monophosphate and phosphatidylinositol 3- monophosphate (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.103

Intolerance Scores

LoFtool: 0.464
RVIS EVS: 0.45
RVIS percentile EVS: 78.02

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.824

Gene Damage Prediction

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