GIT1

Summary

GIT1 (GIT ArfGAP 1, HGNC:4272) is a protein-coding gene on chromosome 17q11.2, encoding ARF GTPase-activating protein GIT1 (Q9Y2X7). GTPase-activating protein for ADP ribosylation factor family members, including ARF1.

Enables gamma-tubulin binding activity. Involved in positive regulation of microtubule nucleation and regulation of cytokinesis. Located in several cellular components, including focal adhesion; microtubule cytoskeleton; and mitochondrion. Implicated in attention deficit hyperactivity disorder. Biomarker of Huntington’s disease.

Source: NCBI Gene 28964 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 120 total — 2 pathogenic
• MANE Select transcript: NM_014030

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4272
Approved symbol	GIT1
Name	GIT ArfGAP 1
Location	17q11.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000108262
Ensembl biotype	protein_coding
OMIM	608434
Entrez	28964

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 22 protein_coding, 5 retained_intron, 1 nonsense_mediated_decay

ENST00000225394, ENST00000335356, ENST00000394869, ENST00000473217, ENST00000491377, ENST00000577466, ENST00000578266, ENST00000578670, ENST00000579536, ENST00000579937, ENST00000581348, ENST00000581925, ENST00000583413, ENST00000585148, ENST00000586574, ENST00000923336, ENST00000923337, ENST00000923338, ENST00000923339, ENST00000923340, ENST00000923341, ENST00000923342, ENST00000923343, ENST00000923344, ENST00000958194, ENST00000958195, ENST00000958196, ENST00000958197

RefSeq mRNA: 2 — MANE Select: NM_014030 NM_001085454, NM_014030

CCDS: CCDS11250, CCDS42290

Canonical transcript exons

ENST00000225394 — 20 exons

Exon	Start	End
ENSE00001127716	29581338	29581380
ENSE00001836488	29589327	29589648
ENSE00002205082	29575630	29575703
ENSE00002802011	29583483	29583616
ENSE00003467879	29581927	29582144
ENSE00003474827	29576522	29576674
ENSE00003507599	29578299	29578371
ENSE00003516651	29576220	29576450
ENSE00003531595	29578731	29578779
ENSE00003545877	29575812	29575898
ENSE00003600136	29582698	29582803
ENSE00003624217	29575079	29575142
ENSE00003631451	29575288	29575470
ENSE00003640111	29577645	29577742
ENSE00003645503	29576863	29576996
ENSE00003650596	29577136	29577247
ENSE00003650634	29581742	29581836
ENSE00003656550	29576078	29576131
ENSE00003667497	29573475	29574914
ENSE00003758781	29582925	29583037

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 97.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.1637 / max 201.6748, expressed in 1787 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165157	12.6869	1778
165156	1.2952	916
165158	0.8445	511
165155	0.7036	438
165154	0.5763	238
165152	0.0573	21

Top tissues by expression

292 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right frontal lobe	UBERON:0002810	97.58	gold quality
cingulate cortex	UBERON:0003027	97.38	gold quality
anterior cingulate cortex	UBERON:0009835	97.38	gold quality
olfactory bulb	UBERON:0002264	97.24	gold quality
left testis	UBERON:0004533	97.20	gold quality
amygdala	UBERON:0001876	97.12	gold quality
prefrontal cortex	UBERON:0000451	97.10	gold quality
putamen	UBERON:0001874	97.08	gold quality
cerebellar vermis	UBERON:0004720	97.08	gold quality
right testis	UBERON:0004534	96.96	gold quality
cortical plate	UBERON:0005343	96.88	gold quality
sural nerve	UBERON:0015488	96.86	gold quality
nucleus accumbens	UBERON:0001882	96.77	gold quality
caudate nucleus	UBERON:0001873	96.41	gold quality
vena cava	UBERON:0004087	96.25	gold quality
tibial nerve	UBERON:0001323	96.23	gold quality
type B pancreatic cell	CL:0000169	96.17	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.82	gold quality
frontal cortex	UBERON:0001870	95.75	gold quality
right lung	UBERON:0002167	95.69	gold quality
neocortex	UBERON:0001950	95.67	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.31	gold quality
ganglionic eminence	UBERON:0004023	95.24	gold quality
testis	UBERON:0000473	95.12	gold quality
telencephalon	UBERON:0001893	95.02	gold quality
cerebellar cortex	UBERON:0002129	94.84	gold quality
cerebellar hemisphere	UBERON:0002245	94.84	gold quality
forebrain	UBERON:0001890	94.57	gold quality
Ammon’s horn	UBERON:0001954	94.54	gold quality
cerebral cortex	UBERON:0000956	94.44	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.88

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): DDIT3, PURA, SP1

miRNA regulators (miRDB)

69 targeting GIT1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-199A-5P	99.51	69.71	1107
HSA-MIR-199B-5P	99.51	69.74	1098
HSA-MIR-1207-5P	99.49	69.11	2983

Literature-anchored findings (GeneRIF, showing 40)

• Cloning of human GIT1 cDNA, and demonstration of GIT1 interaction with PIX and paxillin proteins. (PMID:10896954)
• GIT1 functions in a motile, multi-molecular signaling complex that regulates membrane protrusions and cell migration. (PMID:11896197)
• GIT1 is a novel regulator of PLCgamma function that mediates PLCgamma activation by c-Src and integrates signal transduction by GPCRs and TKRs (PMID:14523024)
• GIT1 is a novel mediator in agonist-dependent signaling in ECs. GIT1 is involved in cell shape changes and may have a role as a negative feedback regulator that augments recovery of cell contraction. (PMID:15016733)
• A protein interaction network links GIT1, an enhancer of huntingtin aggregation, to Huntington disease. (PMID:15383276)
• GIT1 has a role as a scaffold for ERK1/2 activation in focal adhesions (PMID:15923189)
• GTI proteins regulate cytoskeletal dynamics by feedback inhibition of Rac1, they participate in receptor internalization by regulating membrane trafficking between the plasma membrane and endosomes. (PMID:16598076)
• Mass spectrometry was to used to generate a phosphorylation map og GIT1. (PMID:16825424)
• Results suggest that the PAK-PIX-GIT1 complex is critical for Erk-dependent myosin phosphorylation and vascular permeability. (PMID:17429073)
• GIT1 utilizes a focal adhesion targeting-homology domain to bind paxillin. (PMID:17467235)
• The association of PLCgamma1 with complexes containing GIT1 and beta-Pix is essential for its role in integrin-mediated cell spreading and motility. As a component of this complex, PLCgamma1 is also involved in the activation of Cdc42 and Rac1. (PMID:17562871)
• tyrosine phosphorylation of GIT1 by Src kinases may regulate cytoskeletal reorganization downstream of alpha(IIb)beta(3) by bringing the Rac guanine nucleotide exchange factor betaPIX to the vicinity of the integrin (PMID:18211801)
• GIT1 mediates VEGF-induced podosome formation in endothelial cells: critical role for PLCgamma. (PMID:19023093)
• betaPIX and GIT1 regulate the hepatocyte growth factor-induced and Rac1-dependent membrane transport of WAVE2 and consequently, lamellipodia formation. (PMID:19303398)
• Rac3 inhibits adhesion and differentiation of neuronal cells by modifying GIT1 downstream signaling. (PMID:19494130)
• MYO18A is a novel binding partner of the PAK2/betaPIX/GIT1 complex and suggest that MYO18A may play an important role in regulating epithelial cell migration via affecting multiple cell machineries. (PMID:19923322)
• The CC domain of ERK1/2 is necessary for binding to GIT1, for ERK1/2 activation in focal adhesions, and for cell spreading and migration. (PMID:19947948)
• Rac1 affects small GTPase Arf6 via the Arf GTPase-activating protein, GIT1, as key downstream components of the signaling pathway underlying Ras-induced non-apoptotic cell death. (PMID:20713492)
• an intronic single-nucleotide polymorphism in GIT1, the minor allele of which causes reduced GIT1 expression, shows a strong association with ADHD susceptibility (PMID:21499268)
• novel roles for Cat-1 and its interactions with the Arf GTPases and paxillin in oncogenic transformation. (PMID:22807447)
• phosphorylation of GIT1 on serine 46 by PKD3 represents a molecular switch by which GIT1 localization, paxillin trafficking, and cellular protrusive activity are regulated. (PMID:22893698)
• GIT1 SNP rs550818 is not associated with ADHD in the Brazilian sample. (PMID:22897819)
• MAT2B and GIT1 form a scaffold, which recruits and activates MEK and ERK to promote growth and tumorigenesis. (PMID:23325601)
• GIT1-cortactin association through GIT1-Spa homology domain is required for cortactin localization to the leading edge and is essential for endothelial cell directional migration and tumor angiogenesis. (PMID:24265417)
• miRNA-491-5p and GIT1 serve as modulators and biomarkers for oral squamous cell carcinoma invasion and metastasis. (PMID:24335959)
• Results show that GIT1 is targeted by miR-149 to suppress breast cancer cell migration/invasion and metastasis. (PMID:24608434)
• GIT1/betaPIX/Rac1/PAK pathway plays a crucial role in regulating GABA(A)R synaptic stability and hence inhibitory synaptic transmission with important implications for inhibitory plasticity and information processing in the brain. (PMID:25284783)
• Results suggested that cyclic phosphorylation-dephosphorylation at Tyr- 554 of Git1 was crucial for dynamic interactions between Git1 and paxillin/Hic-5 in order to ensure coordinated cell motility. (PMID:25742295)
• Interaction between MAT2B and GIT1 serves as a scaffold and facilitates signaling in multiple steps of the Ras/Raf/MEK/ERK pathway (PMID:25794709)
• MiR-491 has a role in attenuating cancer stem cells-like properties of hepatocellular carcinoma by inhibition of GIT-1/NF-kappaB-mediated EMT (PMID:26188902)
• Data show that G-protein-coupled receptor kinase-interacting protein 1 (GIT1) and semaphorin 4C (SEMA4C) were found to have putative microRNA miR-138 binding sites in their 3’ untranslated region (3’UTRs). (PMID:26283050)
• Data show association of G protein-coupled receptor kinase-interacting protein 1 (GIT1), p21-activated kinase interacting exchange factor (betaPIX), and p21 protein (Cdc42/Rac)-activated kinase 1 (PAK1) with centrosomes. (PMID:27012601)
• we discuss recent findings in key physiological systems that exemplify current understanding of the function of this important regulatory complex. Further, we draw attention to gaps in crucial information that remain to be filled to allow a better understanding of the many roles of the GIT-PIX complex in health and disease (PMID:27182061)
• In astrocytes and neural stem cells, we identified G-protein-coupled receptor kinase-interacting protein 1 (GIT1) as a novel mTOR-binding protein, creating a unique mTOR complex lacking Raptor and Rictor (PMID:27340174)
• miR-195 inhibits chondrocyte migration through targeted regulation of GIT1 expression. (PMID:27922692)
• We show that GIT1, which also contains an ANK domain, inhibits the Notch1-Dll4 signaling pathway by competing with Notch1 ANK domain for binding to RBP-J in stalk cells (PMID:27926858)
• interactions between Cat-1 and its binding partner paxillin are necessary to ensure sufficient Akt activation so that cancer cells are able to grow under anchorage-independent conditions (PMID:28100775)
• There is significant interaction effects of the GIT1 and DRD4 gene variants on impulsivity in Attention Deficit Hyperactivity Disorder. (PMID:28948080)
• Induced association of beta-PIX with GIT1 is essential for the stimulation of intestinal epithelial restitution by activating Rac1, and this signaling pathway is tightly regulated by cellular polyamines. (PMID:29191942)
• Alternative RNA splicing of the G protein-coupled receptor kinase-interacting protein 1 (GIT1) gene is associated with treatment-induced neuroendocrine prostate cancer (t-NEPC) and reprograms its function involving focal adhesions (FA)-mediated signaling and cell processes, which may contribute to t-NEPC development. (PMID:30417466)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	git1	ENSDARG00000039489
mus_musculus	Git1	ENSMUSG00000011877
rattus_norvegicus	Git1	ENSRNOG00000061270

Paralogs (28): ARAP2 (ENSG00000047365), ACAP1 (ENSG00000072818), SMAP2 (ENSG00000084070), ASAP3 (ENSG00000088280), ARFGAP1 (ENSG00000101199), ADAP1 (ENSG00000105963), AGFG2 (ENSG00000106351), SMAP1 (ENSG00000112305), ACAP2 (ENSG00000114331), ARAP3 (ENSG00000120318), ACAP3 (ENSG00000131584), AGAP3 (ENSG00000133612), AGAP2 (ENSG00000135439), APPL2 (ENSG00000136044), GIT2 (ENSG00000139436), ARFGAP2 (ENSG00000149182), ASAP2 (ENSG00000151693), ASAP1 (ENSG00000153317), APPL1 (ENSG00000157500), AGAP1 (ENSG00000157985), AGAP5 (ENSG00000172650), AGFG1 (ENSG00000173744), ADAP2 (ENSG00000184060), ARAP1 (ENSG00000186635), AGAP4 (ENSG00000188234), AGAP6 (ENSG00000204149), AGAP9 (ENSG00000204172), ARFGAP3 (ENSG00000242247)

Protein

Protein identifiers

ARF GTPase-activating protein GIT1 — Q9Y2X7 (reviewed: Q9Y2X7)

Alternative names: Cool-associated and tyrosine-phosphorylated protein 1, G protein-coupled receptor kinase-interactor 1, GRK-interacting protein 1, p95-APP1

All UniProt accessions (9): Q9Y2X7, A0A0C4DGN6, E7EVC2, J3QL89, J3QLH1, J3QQI0, J3QRU8, K7EIX6, K7EN79

UniProt curated annotations — full annotation on UniProt →

Function. GTPase-activating protein for ADP ribosylation factor family members, including ARF1. Multidomain scaffold protein that interacts with numerous proteins and therefore participates in many cellular functions, including receptor internalization, focal adhesion remodeling, and signaling by both G protein-coupled receptors and tyrosine kinase receptors. Through PAK1 activation, positively regulates microtubule nucleation during interphase. Plays a role in the regulation of cytokinesis; for this function, may act in a pathway also involving ENTR1 and PTPN13. May promote cell motility both by regulating focal complex dynamics and by local activation of RAC1. May act as scaffold for MAPK1/3 signal transduction in focal adhesions. Recruits MAPK1/3/ERK1/2 to focal adhesions after EGF stimulation via a Src-dependent pathway, hence stimulating cell migration. Plays a role in brain development and function. Involved in the regulation of spine density and synaptic plasticity that is required for processes involved in learning. Plays an important role in dendritic spine morphogenesis and synapse formation. In hippocampal neurons, recruits guanine nucleotide exchange factors (GEFs), such as ARHGEF7/beta-PIX, to the synaptic membrane. These in turn locally activate RAC1, which is an essential step for spine morphogenesis and synapse formation. May contribute to the organization of presynaptic active zones through oligomerization and formation of a Piccolo/PCLO-based protein network, which includes ARHGEF7/beta-PIX and FAK1. In neurons, through its interaction with liprin-alpha family members, may be required for AMPA receptor (GRIA2/3) proper targeting to the cell membrane. In complex with GABA(A) receptors and ARHGEF7, plays a crucial role in regulating GABA(A) receptor synaptic stability, maintaining GPHN/gephyrin scaffolds and hence GABAergic inhibitory synaptic transmission, by locally coordinating RAC1 and PAK1 downstream effector activity, leading to F-actin stabilization. May also be important for RAC1 downstream signaling pathway through PAK3 and regulation of neuronal inhibitory transmission at presynaptic input. Required for successful bone regeneration during fracture healing. The function in intramembranous ossification may, at least partly, exerted by macrophages in which GIT1 is a key negative regulator of redox homeostasis, IL1B production, and glycolysis, acting through the ERK1/2/NRF2/NFE2L2 axis. May play a role in angiogenesis during fracture healing. In this process, may regulate activation of the canonical NF-kappa-B signal in bone mesenchymal stem cells by enhancing the interaction between NEMO and ‘Lys-63’-ubiquitinated RIPK1/RIP1, eventually leading to enhanced production of VEGFA and others angiogenic factors. Essential for VEGF signaling through the activation of phospholipase C-gamma and ERK1/2, hence may control endothelial cell proliferation and angiogenesis.

Subunit / interactions. Forms homodimers and possibly oligomers. May forms heterooligomers with GIT2. Interacts with G protein-coupled receptor kinases, including GRK2, GRK3, GRK5 and GRK6. Interacts with PPFIA1, PPFIA2 and PPFIA4. Interacts with GRIP1 and forms a ternary complex with PPFIA1 and GRIP1. Directly interacts with ARHGEF7/beta-PIX, forming in vitro a heptameric complex made of a GIT1 dimer and an ARHGEF7 trimer. Directly interacts with PXN/paxillin; this interaction is enhanced in the presence of ARHGEF7. Directly interacts (via C-terminus) with TGFB1I1/Hic-5 (via LD motif 3). Directly interacts with PTK2/FAK1. May interact with PTK2B/PYK2; this interaction may be indirect. Interacts with AMPA receptors GRIA2/3. Directly interacts with protein Piccolo/PCLO. Forms a complex with Ephrin-B1/EFNB1 and NCK2/GRB4 (via SH2); this interaction is important for spine morphogenesis and synapse formation. Interaction with NCK2 is transient and depends upon GIT1 phosphorylation at Tyr-383. Interacts with GRIN3A/GluN3A (via C-terminus); this interaction competes with GIT1 interaction with ARHGEF7 and limits synaptic localization of GIT1. Interacts with IKBKG/NEMO in resting bone mesenchymal stem cells, as well as in TNF-stimulated cells; this interaction may increase IKBKG affinity for ‘Lys-63’-linked polyubiquitin chains. Interacts with GABA(A) receptors, including GABRB3 and GABRG2. Interacts with SCRIB. Interacts (via N- and C-terminus) with ENTR1/SDCCAG3 (via N-terminus); this interaction is direct. May form a tripartite complex with ENTR1 and PTPN13. Interacts with YWHAZ. Interacts with PAK1. Interacts with PAK3. Directly interacts (via N-terminus) with gamma-tubulin. Interacts with MAPK1 and MAPK3; this interaction is required for MAPK1/3 recruitment to focal adhesions.

Subcellular location. Cytoplasm. Synapse. Presynapse. Postsynapse. Postsynaptic density. Cell junction. Focal adhesion. Cell projection. Lamellipodium. Cytoskeleton. Microtubule organizing center. Centrosome. Spindle pole.

Post-translational modifications. Phosphorylated by PAK1. Phosphorylation on tyrosine residues may be catalyzed by PTK2/FAK1 and SRC in growing fibroblasts. Phosphorylation at Tyr-383 is induced by activation of Ephrin-B1/EFNB1 and catalyzed by SRC family kinases. It is required for the interaction with NCK2 and for GIT1 recruitment to synapses in hippocampal neurons.

Domain organisation. The coiled coil region mediates dimerization.

Induction. Up-regulated at the transcriptional level by MYC.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9Y2X7-1	1	yes
Q9Y2X7-2	2
Q9Y2X7-3	3

RefSeq proteins (2): NP_001078923, NP_054749* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001164	ArfGAP_dom	Domain
IPR002110	Ankyrin_rpt	Repeat
IPR013724	GIT_SHD	Domain
IPR022018	GIT1_C	Domain
IPR032352	GIT1/2_CC	Domain
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR037278	ARFGAP/RecO	Homologous_superfamily
IPR038508	ArfGAP_dom_sf	Homologous_superfamily
IPR047161	GIT-like	Family

Pfam: PF01412, PF08518, PF12205, PF12796, PF16559

UniProt features (52 total): modified residue 25, region of interest 12, compositionally biased region 3, repeat 3, splice variant 3, chain 1, domain 1, coiled-coil region 1, zinc finger region 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y2X7-F1	74.72	0.55

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (25): 224, 359, 362, 364, 370, 375, 383, 385, 388, 392, 410, 413, 417, 480, 498, 536, 537, 545, 554, 561 …

Mutagenesis-validated functional residues (1):

Position	Phenotype
39	when transfected to cells, increased number of multinucleated cells.

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-3928664	Ephrin signaling
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9013404	RAC2 GTPase cycle
R-HSA-9013406	RHOQ GTPase cycle
R-HSA-9013409	RHOJ GTPase cycle
R-HSA-9013420	RHOU GTPase cycle
R-HSA-9013423	RAC3 GTPase cycle
R-HSA-9013424	RHOV GTPase cycle
R-HSA-9619229	Activation of RAC1 downstream of NMDARs

MSigDB gene sets: 443 (showing top): GOBP_DENDRITE_DEVELOPMENT, RNGTGGGC_UNKNOWN, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_NEGATIVE_REGULATION_OF_INTERLEUKIN_1_PRODUCTION, GOBP_INFLAMMATORY_RESPONSE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GCANCTGNY_MYOD_Q6, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_DENDRITIC_SPINE_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS

GO Biological Process (25): immunological synapse formation (GO:0001771), intramembranous ossification (GO:0001957), brain development (GO:0007420), locomotory behavior (GO:0007626), regulation of G protein-coupled receptor signaling pathway (GO:0008277), regulation of ARF protein signal transduction (GO:0032012), negative regulation of ARF protein signal transduction (GO:0032013), regulation of cytokinesis (GO:0032465), negative regulation of interleukin-1 beta production (GO:0032691), synaptic vesicle recycling (GO:0036465), cell redox homeostasis (GO:0045454), negative regulation of glycolytic process (GO:0045820), ephrin receptor signaling pathway (GO:0048013), dendritic spine development (GO:0060996), motor learning (GO:0061743), cellular response to lipopolysaccharide (GO:0071222), cellular response to epidermal growth factor stimulus (GO:0071364), positive regulation of microtubule nucleation (GO:0090063), presynaptic modulation of chemical synaptic transmission (GO:0099171), neurotransmitter receptor localization to postsynaptic specialization membrane (GO:0099645), negative regulation of inflammatory response to wounding (GO:0106015), regulation of synaptic vesicle exocytosis (GO:2000300), positive regulation of receptor catabolic process (GO:2000646), neuron development (GO:0048666), maintenance of postsynaptic specialization structure (GO:0098880)

GO Molecular Function (12): GTPase activator activity (GO:0005096), zinc ion binding (GO:0008270), protein phosphatase binding (GO:0019903), small GTPase binding (GO:0031267), identical protein binding (GO:0042802), gamma-tubulin binding (GO:0043015), protein-containing complex binding (GO:0044877), scaffold protein binding (GO:0097110), structural constituent of postsynaptic specialization (GO:0098879), protein tyrosine kinase binding (GO:1990782), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (25): mitochondrion (GO:0005739), endosome (GO:0005768), centrosome (GO:0005813), cytosol (GO:0005829), focal adhesion (GO:0005925), postsynaptic density (GO:0014069), membrane (GO:0016020), lamellipodium (GO:0030027), dendrite (GO:0030425), growth cone (GO:0030426), neuron projection (GO:0043005), calyx of Held (GO:0044305), synapse (GO:0045202), excitatory synapse (GO:0060076), inhibitory synapse (GO:0060077), mitotic spindle pole (GO:0097431), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978), GABA-ergic synapse (GO:0098982), spindle pole (GO:0000922), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cell projection (GO:0042995), anchoring junction (GO:0070161), presynapse (GO:0098793)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
RHO GTPase cycle	8
EPH-Ephrin signaling	1
Post NMDA receptor activation events	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
synapse	5
cellular anatomical structure	4
ARF protein signal transduction	2
protein binding	2
binding	2
postsynaptic specialization	2
cytoplasm	2
plasma membrane bounded cell projection	2
cell-cell recognition	1
lymphocyte activation	1
direct ossification	1
central nervous system development	1
animal organ development	1
head development	1
behavior	1
G protein-coupled receptor signaling pathway	1
regulation of signal transduction	1
regulation of small GTPase mediated signal transduction	1
regulation of ARF protein signal transduction	1
negative regulation of small GTPase mediated signal transduction	1
cytokinesis	1
regulation of cell cycle process	1
regulation of cell division	1
interleukin-1 beta production	1
regulation of interleukin-1 beta production	1
negative regulation of interleukin-1 production	1
transport	1
establishment of localization in cell	1
synaptic vesicle cycle	1
cellular homeostasis	1
glycolytic process	1
regulation of glycolytic process	1
negative regulation of purine nucleotide catabolic process	1
negative regulation of carbohydrate metabolic process	1
negative regulation of ATP metabolic process	1
cell surface receptor protein tyrosine kinase signaling pathway	1
dendrite development	1
anatomical structure development	1
learning	1
response to lipopolysaccharide	1

Protein interactions and networks

STRING

1658 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GIT1	ARHGEF6	Q15052	998
GIT1	GRK6	P43250	998
GIT1	GRK4	P32298	998
GIT1	ARHGEF7	Q14155	998
GIT1	PXN	P49023	997
GIT1	GRK5	P34947	997
GIT1	GRK2	P25098	993
GIT1	SCRIB	Q14160	920
GIT1	CDC42	P21181	871
GIT1	PAK3	O75914	800
GIT1	NCK2	O43639	795
GIT1	PPFIA3	O75145	723
GIT1	PAK1	Q13153	721
GIT1	PPFIA1	Q13136	709
GIT1	AKT1	P31749	705

IntAct

195 interactions, top by confidence:

A	B	Type	Score
ARHGEF7	PAK1	psi-mi:“MI:0914”(association)	0.950
SCRIB	ARHGEF7	psi-mi:“MI:0914”(association)	0.940
PAK1	NCK2	psi-mi:“MI:0914”(association)	0.940
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
PAK2	NCK2	psi-mi:“MI:0914”(association)	0.840
SCRIB	ADRA1D	psi-mi:“MI:0914”(association)	0.820
ARHGEF7	GIT1	psi-mi:“MI:0915”(physical association)	0.820
PAK2	ARHGEF7	psi-mi:“MI:0914”(association)	0.810
ARHGEF6	PAK1	psi-mi:“MI:0914”(association)	0.800
NHERF2	PODXL	psi-mi:“MI:0914”(association)	0.770
GIT1	PFDN1	psi-mi:“MI:0915”(physical association)	0.750
FBXO28	TRAF5	psi-mi:“MI:0914”(association)	0.740
MED4	MED14	psi-mi:“MI:0914”(association)	0.740
NCK1	WASL	psi-mi:“MI:0914”(association)	0.740
GIT1	SCRIB	psi-mi:“MI:0915”(physical association)	0.740
GIT1	PAK1	psi-mi:“MI:0915”(physical association)	0.740
SCRIB	PPP1CC	psi-mi:“MI:0914”(association)	0.730
NCK1	NCK2	psi-mi:“MI:0914”(association)	0.730
PSMC5	PSMD11	psi-mi:“MI:0914”(association)	0.730
TAX1BP3	ARVCF	psi-mi:“MI:0914”(association)	0.690

BioGRID (293): GIT1 (Affinity Capture-MS), GIT1 (Affinity Capture-MS), GIT1 (Affinity Capture-MS), GIT1 (Affinity Capture-MS), GIT1 (Affinity Capture-MS), GIT1 (Affinity Capture-MS), GIT1 (Proximity Label-MS), GIT1 (Affinity Capture-MS), GIT1 (Affinity Capture-MS), GIT1 (Affinity Capture-MS), GIT1 (Affinity Capture-MS), GIT1 (Affinity Capture-MS), GIT1 (Affinity Capture-MS), GIT1 (Affinity Capture-MS), GIT1 (Affinity Capture-MS)

ESM2 similar proteins: A0JNA8, A2AFR3, A2AWP8, F1LXF1, O15034, O94844, O94967, O95267, P11274, P28028, Q01826, Q08BT5, Q14161, Q14CM0, Q15139, Q3UGM2, Q3UHE1, Q4R4I0, Q5R5M3, Q5VUG0, Q5XIS9, Q60611, Q62101, Q66H91, Q68FF6, Q6NZQ4, Q6PAJ1, Q6PB44, Q6ZW49, Q6ZWH5, Q80U28, Q8BWW9, Q8BZ03, Q8CGF6, Q8TCU6, Q8VDD9, Q8VI24, Q96GD3, Q9BZ71, Q9BZL6

Diamond homologs: A1L520, A1Z7A6, A5PK26, A6NIR3, O43150, O74345, O75689, O80925, O82171, O94601, O97902, P35197, P38682, P40529, P52594, Q04412, Q09531, Q0WQQ1, Q10165, Q10367, Q14161, Q15027, Q15057, Q17R07, Q1AAU6, Q1ZXH8, Q28CM8, Q2TA45, Q3MID3, Q3UHD9, Q4KLH5, Q4KLN7, Q4LDD4, Q4R4C9, Q5F413, Q5FVC7, Q5R787, Q5RAT7, Q5U464, Q5VTM2

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
GIT1	up-regulates	PLCG1	binding
PRKD3	unknown	GIT1	phosphorylation
MAT2B	“up-regulates activity”	GIT1	binding
GIT1	“up-regulates activity”	MAP2K1	binding
GIT1	“up-regulates activity”	ARHGEF6	binding
RAC1	“up-regulates activity”	GIT1	binding
GIT1	“up-regulates activity”	ARF6	“guanine nucleotide exchange factor”
SRC	“up-regulates activity”	GIT1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 157 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	5	29.7×	4e-05
RHOV GTPase cycle	9	22.7×	1e-07
RHOU GTPase cycle	8	19.7×	1e-06
RHO GTPases activate PKNs	7	19.6×	7e-06
RHOQ GTPase cycle	9	14.4×	2e-06
RHOJ GTPase cycle	7	12.4×	8e-05
GSK3B-mediated proteasomal degradation of PD-L1(CD274)	5	10.5×	2e-03
SPOP-mediated proteasomal degradation of PD-L1(CD274)	5	10.1×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
chromosome segregation	9	11.0×	1e-04
microtubule cytoskeleton organization	8	6.8×	7e-03
cell migration	12	5.2×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

120 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	71
Likely benign	14
Benign	3

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
4281611	NM_014030.4(GIT1):c.1094-1_1096del	Pathogenic
4281612	NM_014030.4(GIT1):c.1541dup (p.Ala515fs)	Pathogenic

SpliceAI

2638 predictions. Top by Δscore:

Variant	Effect	Δscore
17:29575138:CGAAG:C	acceptor_gain	1.0000
17:29575139:GAAG:G	acceptor_gain	1.0000
17:29575140:AAGC:A	acceptor_loss	1.0000
17:29575141:AG:A	acceptor_gain	1.0000
17:29575141:AGC:A	acceptor_loss	1.0000
17:29575142:GC:G	acceptor_loss	1.0000
17:29575143:C:CC	acceptor_gain	1.0000
17:29575144:T:G	acceptor_loss	1.0000
17:29575283:AGTAC:A	donor_gain	1.0000
17:29575286:A:AC	donor_gain	1.0000
17:29575286:ACCTG:A	donor_loss	1.0000
17:29575287:C:CC	donor_gain	1.0000
17:29575287:CCTGT:C	donor_gain	1.0000
17:29575324:T:A	donor_gain	1.0000
17:29575466:CCAGC:C	acceptor_gain	1.0000
17:29575467:CAGCC:C	acceptor_gain	1.0000
17:29575479:C:CT	acceptor_gain	1.0000
17:29575480:A:T	acceptor_gain	1.0000
17:29575485:C:CT	acceptor_gain	1.0000
17:29575485:C:T	acceptor_gain	1.0000
17:29575486:A:T	acceptor_gain	1.0000
17:29575492:C:CT	acceptor_gain	1.0000
17:29575493:A:T	acceptor_gain	1.0000
17:29575507:A:C	acceptor_gain	1.0000
17:29575702:CT:C	acceptor_gain	1.0000
17:29575704:C:CC	acceptor_gain	1.0000
17:29576213:GACT:G	donor_loss	1.0000
17:29576214:ACTC:A	donor_loss	1.0000
17:29576215:CTCA:C	donor_loss	1.0000
17:29576216:TCACA:T	donor_loss	1.0000

AlphaMissense

4962 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:29574733:A:G	V752A	1.000
17:29574733:A:T	V752D	1.000
17:29574736:A:C	L751R	1.000
17:29574736:A:G	L751P	1.000
17:29574736:A:T	L751Q	1.000
17:29574739:T:G	Q750P	1.000
17:29574741:C:A	K749N	1.000
17:29574741:C:G	K749N	1.000
17:29574742:T:A	K749M	1.000
17:29574743:T:C	K749E	1.000
17:29574745:G:T	A748D	1.000
17:29574746:C:G	A748P	1.000
17:29574748:G:T	A747D	1.000
17:29574749:C:G	A747P	1.000
17:29574750:C:A	K746N	1.000
17:29574750:C:G	K746N	1.000
17:29574754:G:A	A745V	1.000
17:29574754:G:T	A745D	1.000
17:29574755:C:G	A745P	1.000
17:29574757:A:C	I744S	1.000
17:29574757:A:T	I744N	1.000
17:29574764:A:C	Y742D	1.000
17:29574764:A:G	Y742H	1.000
17:29574764:A:T	Y742N	1.000
17:29574766:G:T	A741D	1.000
17:29574767:C:G	A741P	1.000
17:29574775:A:C	I738S	1.000
17:29574775:A:T	I738N	1.000
17:29574840:G:C	C716W	1.000
17:29574841:C:T	C716Y	1.000

dbSNP variants (sampled 300 via entrez): RS1000175695 (17:29576336 T>C), RS1000196818 (17:29591122 C>T), RS1000227959 (17:29576095 G>C,T), RS1000500862 (17:29581774 C>A,T), RS1000551274 (17:29574498 G>A,T), RS1000870808 (17:29585898 G>A), RS1000956869 (17:29585821 GAACT>G), RS1001001385 (17:29579659 G>A,C), RS1001106829 (17:29580537 G>A), RS1001218093 (17:29582612 C>T), RS1001357830 (17:29585852 C>A), RS1001456607 (17:29580708 G>A), RS1002280529 (17:29586641 G>A), RS1002286972 (17:29580618 G>A), RS1002446977 (17:29575062 C>T)

Disease associations

OMIM: gene MIM:608434 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST010703_115	Brain morphology (MOSTest)	1.000000e-28
GCST010988_58	Adult body size	8.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

34 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, decreases expression	3
sodium arsenite	decreases expression, increases abundance	2
Acetaminophen	increases expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
2,4,6-tribromophenol	decreases expression	1
decabromobiphenyl ether	increases expression	1
tetrabromobisphenol A	decreases expression	1
coumarin	affects phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
abrine	decreases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Bortezomib	decreases expression	1
Sunitinib	increases expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Arsenic	decreases expression, increases abundance	1
Atrazine	increases expression	1
Caffeine	affects phosphorylation	1
Calcium Chloride	increases expression	1
Cisplatin	increases expression, affects cotreatment	1
Dactinomycin	affects cotreatment, increases secretion	1
Diazinon	increases methylation	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Smoke	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1SV	Abcam HeLa GIT1 KO	Cancer cell line	Female
CVCL_SQ02	HAP1 GIT1 (-) 1	Cancer cell line	Male
CVCL_XP12	HAP1 GIT1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.