GDI2

protein-coding

GDP dissociation inhibitor 2

Gene summary

GDP dissociation inhibitors are proteins that regulate the GDP-GTP exchange reaction of members of the rab family, small GTP-binding proteins of the ras superfamily, that are involved in vesicular trafficking of molecules between cellular organelles. GDIs slow the rate of dissociation of GDP from rab proteins and release GDP from membrane-bound rabs. GDI2 is ubiquitously expressed. The GDI2 gene contains many repetitive elements indicating that it may be prone to inversion/deletion rearrangements. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001494.4

Inheritance

—

ClinVar variants

U:50B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.17

Max pathogenic AF

—

Genomic locus

chr10:5,765,222-5,842,132

External References & Databases

Ensembl (ENSG00000057608)

Transcript & Mutation Effects

hg38 • Region Span ~76.9 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 GDI2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 40

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001494.4. 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			3 clinvar			3
missense			41 clinvar	1 clinvar	1 clinvar	43
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	50	1	1	52

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 46 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001494.4	RefSeq	NP_001485.2	11	MANE Select
ENST00000380191.9	Ensembl	ENSP00000369538.4	11	MANE Select
NM_001115156.2	RefSeq	NP_001108628.1	10	Standard
ENST00000380127.5	Ensembl	ENSP00000369470.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Neutrophil degranulation
Signal Transduction
Vesicle-mediated transport
Membrane Trafficking
TCR

Biological Process

signal transduction
small GTPase mediated signal transduction
protein transport
neutrophil degranulation
positive regulation of GTPase activity

Molecular Function

RNA binding
Rab GDP-dissociation inhibitor activity
GTPase activator activity
protein binding
small GTPase binding

Cellular Component

extracellular region
cytoplasm
Golgi apparatus
cytosol
focal adhesion

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000380191
Coding exons: 11
Length: 76910
Individuals with no LoFs: 125739
Homozygous LoFs: 0
Heterozygous LoFs: 9
Defined: 125748
p: 0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.72	171	247	0.692	0.0000126	2933
Missense (PolyPhen)		18	63.332	0.28422		780
Synonymous	1.70	65	84.9	0.765	0.00000450	817
Loss of Function	3.76	4	23.8	0.168	0.00000121	305

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	0.000046	0.000046	rare
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0.000068	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Regulates the GDP/GTP exchange reaction of most Rab proteins by inhibiting the dissociation of GDP from them, and the subsequent binding of GTP to them.;

Recessive Scores

pRec: 0.209

Intolerance Scores

LoFtool: 0.0651
RVIS EVS: -0.12
RVIS percentile EVS: 45.13

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): K
Indispensability pred.: E
Indispensability score: 0.992

Gene Damage Prediction

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