GIT2

protein-coding

GIT ArfGAP 2, the group of ArfGAPs|Ankyrin repeat domain containing

Gene summary

This gene encodes a member of the GIT protein family, which interact with G protein-coupled receptor kinases and possess ADP-ribosylation factor (ARF) GTPase-activating protein (GAP) activity. GIT proteins traffic between cytoplasmic complexes, focal adhesions, and the cell periphery, and interact with Pak interacting exchange factor beta (PIX) to form large oligomeric complexes that transiently recruit other proteins. GIT proteins regulate cytoskeletal dynamics and participate in receptor internalization and membrane trafficking. This gene has been shown to repress lamellipodial extension and focal adhesion turnover, and is thought to regulate cell motility. This gene undergoes extensive alternative splicing to generate multiple isoforms, but the full-length nature of some of these variants has not been determined. The various isoforms have functional differences, with respect to ARF GAP activity and to G protein-coupled receptor kinase 2 binding. [provided by RefSeq, Sep 2008]

MANE transcript

NM_057169.5

Inheritance

—

ClinVar variants

U:100B:9

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.13

Max pathogenic AF

—

Genomic locus

chr12:109,929,804-109,996,389

External References & Databases

Ensembl (ENSG00000139436)

Transcript & Mutation Effects

hg38 • Region Span ~66.6 kb

Loading mutation effect viewer...

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 GIT2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 86

not providedTotal: 7

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_057169.5. 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			4 clinvar		3 clinvar	7
missense			87 clinvar	5 clinvar	1 clinvar	93
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	0	100	5	4	109

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 86 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_057169.5	RefSeq	NP_476510.1	20	MANE Select
ENST00000355312.8	Ensembl	ENSP00000347464.3	20	MANE Select
NM_001135213.3	RefSeq	NP_001128685.1	19	Standard
NM_001135214.3	RefSeq	NP_001128686.1	19	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
git2a	Danio rerio	Structure: post-vent region Quality: kinked abnormal

Gene / Model

Organism

Observed Phenotype

git2a

Danio rerio

Structure: post-vent region

Quality: kinked

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Endocytosis - Homo sapiens (human)
Integrin-mediated Cell Adhesion
TCR
EGFR1
agrin in postsynaptic differentiation

Biological Process

regulation of G protein-coupled receptor signaling pathway
positive regulation of GTPase activity

Molecular Function

GTPase activator activity
protein binding
metal ion binding

Cellular Component

nucleoplasm
focal adhesion

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000355312
Coding exons: 20
Length: 66588
Individuals with no LoFs: 125736
Homozygous LoFs: 0
Heterozygous LoFs: 10
Defined: 125746
p: 0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.34	315	456	0.691	0.0000264	4995
Missense (PolyPhen)		101	178.53	0.56572		1959
Synonymous	0.806	167	181	0.924	0.0000123	1447
Loss of Function	5.35	6	44.5	0.135	0.00000229	502

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00014	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000035	0.000035	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: GTPase-activating protein for the ADP ribosylation factor family.;

Recessive Scores

pRec: 0.112

Intolerance Scores

LoFtool: 0.444
RVIS EVS: -0.51
RVIS percentile EVS: 21.73

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.971

Gene Damage Prediction

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