TIAM2

Summary

TIAM2 (TIAM Rac1 associated GEF 2, HGNC:11806) is a protein-coding gene on chromosome 6q25.2-q25.3, encoding Rho guanine nucleotide exchange factor TIAM2 (Q8IVF5). Modulates the activity of RHO-like proteins and connects extracellular signals to cytoskeletal activities.

This gene encodes a guanine nucleotide exchange factor. A highly similar mouse protein specifically activates ras-related C3 botulinum substrate 1, converting this Rho-like guanosine triphosphatase (GTPase) from a guanosine diphosphate-bound inactive state to a guanosine triphosphate-bound active state. The encoded protein may play a role in neural cell development. Alternatively spliced transcript variants encoding different isoforms have been described.

Source: NCBI Gene 26230 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 202 total
• MANE Select transcript: NM_012454

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11806
Approved symbol	TIAM2
Name	TIAM Rac1 associated GEF 2
Location	6q25.2-q25.3
Locus type	gene with protein product
Status	Approved
Aliases	STEF
Ensembl gene	ENSG00000146426
Ensembl biotype	protein_coding
OMIM	604709
Entrez	26230

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 17 protein_coding, 5 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000275246, ENST00000360366, ENST00000431620, ENST00000449545, ENST00000456877, ENST00000460692, ENST00000461783, ENST00000462408, ENST00000528391, ENST00000528535, ENST00000529824, ENST00000535064, ENST00000535231, ENST00000535583, ENST00000537845, ENST00000538270, ENST00000539296, ENST00000543712, ENST00000546145, ENST00000682666, ENST00000929431, ENST00000950123, ENST00000950124, ENST00000950125, ENST00000950126

RefSeq mRNA: 4 — MANE Select: NM_012454 NM_001010927, NM_001384546, NM_001384547, NM_012454

CCDS: CCDS34558, CCDS34559

Canonical transcript exons

ENST00000682666 — 27 exons

Exon	Start	End
ENSE00001318430	155127490	155127600
ENSE00001417153	155256484	155257723
ENSE00001443718	155090289	155090379
ENSE00002146109	155250913	155251021
ENSE00002156428	155252948	155253053
ENSE00002167485	155245623	155245731
ENSE00002168951	155251945	155252003
ENSE00002171739	155248000	155248179
ENSE00002201645	155249851	155249969
ENSE00002218261	154995315	154995492
ENSE00002258639	155182226	155182318
ENSE00002283904	155183237	155183500
ENSE00002284526	155176816	155176977
ENSE00002293728	155179378	155179456
ENSE00002296129	155179039	155179143
ENSE00002314865	155165263	155165409
ENSE00002318443	155211204	155211307
ENSE00003458275	155240530	155240709
ENSE00003464244	155253973	155254060
ENSE00003474386	155244011	155244079
ENSE00003477313	155164415	155164600
ENSE00003492767	155129218	155130417
ENSE00003495103	155137177	155137612
ENSE00003594329	155148110	155148334
ENSE00003621266	155254419	155254573
ENSE00003653153	155244658	155244783
ENSE00003654116	155144606	155144778

Expression profiles

Bgee: expression breadth ubiquitous, 243 present calls, max score 97.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.2237 / max 456.4527, expressed in 1130 samples.

FANTOM5 promoters (30 alternative TSS)

Promoter ID	TPM avg	Samples expressed
70680	3.1131	832
70687	2.9637	172
70688	0.7730	95
70708	0.6432	132
70712	0.3058	65
70690	0.3049	151
70704	0.3023	102
70689	0.2731	91
70713	0.2273	57
70681	0.1585	82

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	97.73	gold quality
embryo	UBERON:0000922	96.76	gold quality
ganglionic eminence	UBERON:0004023	96.76	gold quality
ventricular zone	UBERON:0003053	95.51	gold quality
cartilage tissue	UBERON:0002418	95.23	gold quality
middle temporal gyrus	UBERON:0002771	94.04	gold quality
tibia	UBERON:0000979	91.58	gold quality
Brodmann (1909) area 23	UBERON:0013554	91.53	gold quality
primary visual cortex	UBERON:0002436	91.41	gold quality
pancreatic ductal cell	CL:0002079	90.68	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.91	gold quality
prefrontal cortex	UBERON:0000451	89.86	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	89.32	gold quality
calcaneal tendon	UBERON:0003701	89.13	gold quality
right frontal lobe	UBERON:0002810	89.04	gold quality
frontal cortex	UBERON:0001870	88.92	gold quality
neocortex	UBERON:0001950	88.71	gold quality
occipital lobe	UBERON:0002021	88.61	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.37	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.09	gold quality
right testis	UBERON:0004534	87.77	gold quality
left testis	UBERON:0004533	87.63	gold quality
adrenal tissue	UBERON:0018303	87.61	gold quality
superior frontal gyrus	UBERON:0002661	86.60	gold quality
cerebral cortex	UBERON:0000956	86.46	gold quality
testis	UBERON:0000473	86.39	gold quality
anterior cingulate cortex	UBERON:0009835	86.15	gold quality
secondary oocyte	CL:0000655	85.33	gold quality
Brodmann (1909) area 46	UBERON:0006483	85.06	gold quality
gastrocnemius	UBERON:0001388	84.97	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-6379	no	11.02
E-ANND-3	no	5.94

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

76 targeting TIAM2, 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-1277-5P	100.00	73.95	5056
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489

Literature-anchored findings (GeneRIF, showing 11)

• STEF protein is a guanine nucleotide exchange factor that specifically activates Rac1 in vitro and in cultured cells, which may lead to changes in the actin cytoskeletal network. (PMID:10364228)
• stef gene expressed in a stage- and region-specific manner in the mouse brain (PMID:11900975)
• TIAM2 expression was undetectable in normal human liver but was induced in all HCC cell lines and in 86% (78/91) of HCC biopsies. (PMID:21469146)
• Knockdown of TIAM2 could up-regulate the expression of E-cadherin. (PMID:24377522)
• Results provide evidence that Sp1 positively controls TIAM2S transcription and that Sp1-mediated transcriptional activation is essential for TIAM2S ectopic expression in liver cancer cells. (PMID:26763486)
• Tiam2/Rac are key components of EphB2 trans-endocytosis and are important for cell repulsion. (PMID:27597758)
• The authors show that the Rac1 selective guanine nucleotide exchange factor Sif and TIAM1-like Exchange Factor STEF, also known as TIAM2, localises to the nuclear envelope, co-localises with key perinuclear proteins and regulates the activity of perinuclear Rac1. (PMID:29844364)
• Elevated TIAM2 expression promotes tumor progression and is associated with unfavorable prognosis in pancreatic cancer. (PMID:33284659)
• FARP1, ARHGEF39, and TIAM2 are essential receptor tyrosine kinase effectors for Rac1-dependent cell motility in human lung adenocarcinoma. (PMID:34731623)
• TIAM2S-positive microglia enhance inflammation and neurotoxicity through soluble ICAM-1-mediated immune priming. (PMID:37801065)
• Novel genetic markers for chronic kidney disease in a geographically isolated population of Indigenous Australians: Individual and multiple phenotype genome-wide association study. (PMID:38347632)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tiam2a	ENSDARG00000087780
mus_musculus	Tiam2	ENSMUSG00000023800
rattus_norvegicus	Tiam2	ENSRNOG00000016728

Paralogs (22): TRIO (ENSG00000038382), MCF2L2 (ENSG00000053524), PLEKHG2 (ENSG00000090924), MCF2 (ENSG00000101977), ARHGEF7 (ENSG00000102606), PLEKHG1 (ENSG00000120278), MCF2L (ENSG00000126217), ARHGEF6 (ENSG00000129675), ARHGEF9 (ENSG00000131089), VAV3 (ENSG00000134215), VAV1 (ENSG00000141968), KIAA1755 (ENSG00000149633), PLEKHG4B (ENSG00000153404), TIAM1 (ENSG00000156299), KALRN (ENSG00000160145), VAV2 (ENSG00000160293), ARHGEF40 (ENSG00000165801), SPATA13 (ENSG00000182957), SESTD1 (ENSG00000187231), PLEKHN1 (ENSG00000187583), PLEKHG4 (ENSG00000196155), ARHGEF25 (ENSG00000240771)

Protein

Protein identifiers

Rho guanine nucleotide exchange factor TIAM2 — Q8IVF5 (reviewed: Q8IVF5)

Alternative names: SIF and TIAM1-like exchange factor, T-lymphoma invasion and metastasis-inducing protein 2

All UniProt accessions (8): Q8IVF5, E9PKT1, E9PMZ8, F5H1M3, F5H6R0, F5H6W6, H0YGV1, H7C5V6

UniProt curated annotations — full annotation on UniProt →

Function. Modulates the activity of RHO-like proteins and connects extracellular signals to cytoskeletal activities. Acts as a GDP-dissociation stimulator protein that stimulates the GDP-GTP exchange activity of RHO-like GTPases and activates them. Mediates extracellular laminin signals to activate Rac1, contributing to neurite growth. Involved in lamellipodial formation and advancement of the growth cone of embryonic hippocampal neurons. Promotes migration of neurons in the cerebral cortex. When overexpressed, induces membrane ruffling accompanied by the accumulation of actin filaments along the altered plasma membrane. Activates specifically RAC1, but not CDC42 and RHOA.

Subunit / interactions. Interacts with MAP1A, MAP1B, PARP1 and YWHAE. Interacts with CD44, PARD3 and MAPK8IP2.

Subcellular location. Cytoplasm. Cell projection. Lamellipodium. Filopodium. Growth cone. Neuron projection. Perikaryon.

Tissue specificity. Expressed in the occipital, frontal and temporal lobes, cerebellum, putamen and testis.

Post-translational modifications. Phosphorylated on serine and threonine residues. Phosphorylated on Thr-1648 by Rho-kinase. Its phosphorylation by Rho-kinase inhibits its guanine nucleotide exchange activity, its interaction with MAP1A, MAP1B, PARP1 and YWHAE and reduces its ability to promote neurite growth.

Domain organisation. The PH 1 domain and amino acids 621-782 (a region called TSS; otherwise known as CC-Ex) are necessary for membrane localization. The PH 1 and TSS domains are necessary for Rac1 activity. The PH 2 domain is engaged in the enhancement of the catalytic activity of the adjacent DH domain. The PH 1, TSS and DH domains are necessary to induce neurite-like structure.

Similarity. Belongs to the TIAM family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q8IVF5-1	1	yes
Q8IVF5-2	2
Q8IVF5-3	3, Short
Q8IVF5-4	4
Q8IVF5-5	5, Long

RefSeq proteins (4): NP_001010927, NP_001371475, NP_001371476, NP_036586* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000219	DH_dom	Domain
IPR001331	GDS_CDC24_CS	Conserved_site
IPR001478	PDZ	Domain
IPR001849	PH_domain	Domain
IPR003116	RBD_dom	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR035899	DBL_dom_sf	Homologous_superfamily
IPR036034	PDZ_sf	Homologous_superfamily
IPR040655	TIAM1_CC-Ex	Domain
IPR043537	Tiam1/Tiam2/Sif	Family
IPR055230	PH_Tiam1/2	Domain

Pfam: PF00169, PF00595, PF00621, PF18385, PF23014

UniProt features (46 total): sequence conflict 15, region of interest 7, domain 5, sequence variant 5, compositionally biased region 4, splice variant 4, modified residue 2, initiator methionine 1, chain 1, coiled-coil region 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IVF5-F1	56.95	0.19

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 (3): 1583, 1648, 2

Function

Pathways and Gene Ontology

Reactome pathways

16 pathways

ID	Pathway
R-HSA-193648	NRAGE signals death through JNK
R-HSA-1989781	PPARA activates gene expression
R-HSA-416482	G alpha (12/13) signalling events
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-1430728	Metabolism
R-HSA-162582	Signal Transduction
R-HSA-193704	p75 NTR receptor-mediated signalling
R-HSA-194315	Signaling by Rho GTPases
R-HSA-204998	Cell death signalling via NRAGE, NRIF and NADE
R-HSA-372790	Signaling by GPCR
R-HSA-388396	GPCR downstream signalling
R-HSA-400206	Regulation of lipid metabolism by PPARalpha
R-HSA-556833	Metabolism of lipids
R-HSA-73887	Death Receptor Signaling
R-HSA-9012999	RHO GTPase cycle
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 174 (showing top): GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, REACTOME_NRAGE_SIGNALS_DEATH_THROUGH_JNK, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, chr6q25, GGGCATT_MIR365, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, MODULE_205, GOBP_POSITIVE_REGULATION_OF_CELL_DIFFERENTIATION, GROSS_HYPOXIA_VIA_ELK3_DN, GROSS_HYPOXIA_VIA_HIF1A_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, GOBP_REGULATION_OF_NEURON_PROJECTION_DEVELOPMENT, GOCC_NEURON_PROJECTION

GO Biological Process (6): small GTPase-mediated signal transduction (GO:0007264), positive regulation of axonogenesis (GO:0050772), regulation of small GTPase mediated signal transduction (GO:0051056), signal transduction (GO:0007165), intracellular signal transduction (GO:0035556), activation of GTPase activity (GO:0090630)

GO Molecular Function (3): guanyl-nucleotide exchange factor activity (GO:0005085), GTPase activator activity (GO:0005096), protein binding (GO:0005515)

GO Cellular Component (11): cytosol (GO:0005829), membrane (GO:0016020), lamellipodium (GO:0030027), filopodium (GO:0030175), growth cone (GO:0030426), perikaryon (GO:0043204), synapse (GO:0045202), extracellular exosome (GO:0070062), cytoplasm (GO:0005737), cell projection (GO:0042995), neuron projection (GO:0043005)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Signal Transduction	3
Cell death signalling via NRAGE, NRIF and NADE	1
Regulation of lipid metabolism by PPARalpha	1
GPCR downstream signalling	1
RHO GTPase cycle	1
Death Receptor Signaling	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
p75 NTR receptor-mediated signalling	1
Signaling by GPCR	1
Metabolism of lipids	1
Metabolism	1
Signaling by Rho GTPases	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
intracellular anatomical structure	2
GTPase regulator activity	2
plasma membrane bounded cell projection	2
intracellular signaling cassette	1
axonogenesis	1
positive regulation of cell projection organization	1
positive regulation of neurogenesis	1
regulation of axonogenesis	1
small GTPase-mediated signal transduction	1
regulation of intracellular signal transduction	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
signal transduction	1
positive regulation of GTPase activity	1
GTP binding	1
GDP binding	1
GTPase activity	1
enzyme activator activity	1
binding	1
cytoplasm	1
cell leading edge	1
actin-based cell projection	1
site of polarized growth	1
distal axon	1
neuronal cell body	1
cell junction	1
extracellular vesicle	1

Protein interactions and networks

STRING

1240 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TIAM2	RABIF	P47224	721
TIAM2	SCAF8	Q9UPN6	640
TIAM2	CLDN20	P56880	604
TIAM2	PLEK2	Q9NYT0	563
TIAM2	PLEK	P08567	563
TIAM2	GPM6A	P51674	562
TIAM2	A0A2Q2T6B6	A0A2Q2T6B6	546
TIAM2	G9CGD6	G9CGD6	539
TIAM2	CNKSR3	Q6P9H4	536
TIAM2	TIAM1	Q13009	487
TIAM2	CDC42	P21181	464
TIAM2	RHOA	P06749	455
TIAM2	NRXN1	Q9ULB1	431
TIAM2	NOX3	Q9HBY0	422
TIAM2	OPRM1	P35372	418

IntAct

394 interactions, top by confidence:

A	B	Type	Score
NRXN3	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
NECTIN3	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
TIAM2	NECTIN1	psi-mi:“MI:0407”(direct interaction)	0.440
CSPG4	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
CNTNAP4	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
CIB2	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
KCNV1	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
SLC6A3	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
SDC2	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
SIPA1	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
GYPC	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
TRAF7	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
TIAM2	GRIA2	psi-mi:“MI:0407”(direct interaction)	0.440
GJC1	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
PRLHR	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
JAM2	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
MYOT	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
CACNA1D	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
TIAM2	PKN2	psi-mi:“MI:0407”(direct interaction)	0.440
PPFIA1	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
ACTN2	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
TIAM2	JAG1	psi-mi:“MI:0407”(direct interaction)	0.440
GAS2L2	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
RNF130	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
GARIN6	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A9	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
F11R	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
SLC1A1	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A12	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (19): TIAM2 (Affinity Capture-MS), TIAM2 (Proximity Label-MS), TIAM2 (Affinity Capture-RNA), TIAM2 (Proximity Label-MS), TIAM2 (Affinity Capture-RNA), TIAM2 (Affinity Capture-MS), TIAM2 (Cross-Linking-MS (XL-MS)), TIAM2 (Proximity Label-MS), TIAM2 (Proximity Label-MS), TIAM2 (Proximity Label-MS), TIAM2 (Proximity Label-MS), TIAM2 (Two-hybrid), TIAM2 (Two-hybrid), TIAM2 (Two-hybrid), TIAM2 (Two-hybrid)

ESM2 similar proteins: A0A1L8HBI7, A0A1L8HJK9, A0A1L8HTT5, A6NP61, A8T6P4, C0SPG1, C3VD30, F1N4E5, K7SGN7, O35144, O35253, O70240, O88406, O88566, Q15554, Q1XFL1, Q3ZC82, Q4KLH3, Q5HZN9, Q5JTV8, Q5PQX1, Q5R7A3, Q62315, Q68DK7, Q6P1H6, Q6PDM1, Q6PG95, Q6ZPF3, Q76N89, Q7T3T8, Q7T3T9, Q7T3U0, Q7TNY7, Q7TP65, Q7TSX9, Q80SU3, Q80VM8, Q86XL3, Q8IVF5, Q8K3I4

Diamond homologs: A1CEK6, A1DFN5, A2QW93, A4FU49, A4RF61, A7E3N7, B0BNA1, B1V8A0, E2RP94, E7F1U2, F1M0Z1, G5EC32, M0R4F8, O08641, O15068, O35179, O35180, O35413, O35964, O43586, O75962, O94875, P10569, P11433, P19706, P19878, P29355, P34109, P52735, P97814, Q01406, Q06449, Q09822, Q0CJU8, Q0KL02, Q0U6X7, Q14247, Q15080, Q1E878, Q1LUA6

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
TIAM2	“up-regulates activity”	RAC1	“guanine nucleotide exchange factor”
GRK1	“down-regulates activity”	TIAM2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 196 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
Unblocking of NMDA receptors, glutamate binding and activation	5	18.8×	1e-03
Long-term potentiation	5	16.4×	1e-03
Voltage gated Potassium channels	6	10.1×	1e-03
Neurexins and neuroligins	7	9.5×	1e-03
EPHB-mediated forward signaling	5	9.2×	5e-03
RHOQ GTPase cycle	7	8.8×	1e-03
Assembly and cell surface presentation of NMDA receptors	5	8.8×	6e-03
Potassium Channels	9	8.3×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
glutamate receptor signaling pathway	6	30.0×	3e-05
regulation of cardiac conduction	6	27.0×	3e-05
positive regulation of synaptic transmission, glutamatergic	5	16.7×	2e-03
positive regulation of excitatory postsynaptic potential	5	14.1×	3e-03
action potential	7	13.4×	3e-04
maintenance of blood-brain barrier	5	12.9×	4e-03
excitatory postsynaptic potential	5	11.9×	5e-03
synaptic transmission, glutamatergic	5	9.6×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	157
Likely benign	16
Benign	8

Top pathogenic / likely-pathogenic (0)

SpliceAI

9118 predictions. Top by Δscore:

Variant	Effect	Δscore
6:154907845:G:GT	donor_gain	1.0000
6:154944114:A:AG	acceptor_gain	1.0000
6:154944114:AG:A	acceptor_gain	1.0000
6:154944115:G:GT	acceptor_gain	1.0000
6:154944115:GG:G	acceptor_gain	1.0000
6:154944115:GGA:G	acceptor_gain	1.0000
6:154944115:GGAC:G	acceptor_gain	1.0000
6:154944115:GGACA:G	acceptor_gain	1.0000
6:154944166:G:GT	donor_gain	1.0000
6:154944191:GGT:G	donor_gain	1.0000
6:154944193:T:G	donor_gain	1.0000
6:154944203:GCAG:G	donor_gain	1.0000
6:154944204:CAGGT:C	donor_loss	1.0000
6:154944205:AG:A	donor_loss	1.0000
6:154944206:GGTT:G	donor_loss	1.0000
6:154944208:T:A	donor_loss	1.0000
6:155071351:G:GT	donor_gain	1.0000
6:155071383:T:G	donor_gain	1.0000
6:155090376:GTGG:G	donor_gain	1.0000
6:155090377:TGGG:T	donor_loss	1.0000
6:155090378:GG:G	donor_gain	1.0000
6:155090378:GGGT:G	donor_loss	1.0000
6:155090379:GG:G	donor_gain	1.0000
6:155090380:G:GG	donor_gain	1.0000
6:155090380:G:T	donor_loss	1.0000
6:155090381:TAAG:T	donor_loss	1.0000
6:155137557:G:GT	donor_gain	1.0000
6:155137614:T:A	donor_loss	1.0000
6:155144596:T:A	acceptor_gain	1.0000
6:155144602:A:AG	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000005586 (6:155169002 GT>G), RS1000008571 (6:154995281 C>A,G,T), RS1000011309 (6:155218722 T>C), RS1000015471 (6:155198172 G>A), RS1000036094 (6:155241015 T>C), RS1000038157 (6:155198687 A>G), RS1000045766 (6:155128613 A>G), RS1000062581 (6:155122513 T>A), RS1000064855 (6:155118051 C>G,T), RS1000069886 (6:155066930 T>A), RS1000080656 (6:155073108 A>G), RS1000082693 (6:155035397 T>C), RS1000098568 (6:155087601 T>C), RS1000115020 (6:155255116 G>C), RS1000120945 (6:155149430 T>C)

Disease associations

OMIM: gene MIM:604709 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST003127_9	Lipoprotein (a) levels	4.000000e-10
GCST004253_11	Accelerated cognitive decline after conversion of mild cognitive impairment to Alzheimer’s disease (Alzhiemer’s diagnosis trajectory interaction)	8.000000e-06
GCST005756_4	Dimensional psychopathology (Negative)	1.000000e-06
GCST005758_3	Dimensional psychopathology (Arousal)	9.000000e-07
GCST006979_713	Heel bone mineral density	1.000000e-21
GCST006979_714	Heel bone mineral density	3.000000e-13
GCST006979_715	Heel bone mineral density	1.000000e-11
GCST007680_11	Triiodothyronine levels and thyroxine levels	4.000000e-06
GCST009720_42	Asthma	9.000000e-09
GCST012490_649	Femur bone mineral density x serum urate levels interaction	6.000000e-09
GCST90000025_136	Appendicular lean mass	5.000000e-15

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0006925	lipoprotein A measurement
EFO:0007710	cognitive decline measurement
EFO:0009096	negative domain measurement
EFO:0009099	arousal domain measurement
EFO:0009270	heel bone mineral density
EFO:0008392	triiodothyronine measurement
EFO:0004531	urate measurement
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, affects methylation, decreases expression, increases methylation	5
Benzo(a)pyrene	increases methylation, affects methylation, decreases expression	4
Aflatoxin B1	decreases expression, increases methylation	3
Estradiol	affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
pirinixic acid	decreases expression, increases activity, affects binding	1
bisphenol A	decreases methylation	1
trichostatin A	increases expression	1
beta-lapachone	decreases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
mono(2-ethyl-5-oxohexyl)phthalate	increases methylation	1
CGP 52608	increases reaction, affects binding	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Norethindrone Acetate	affects cotreatment, increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Carbamazepine	affects expression	1
Cisplatin	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Formaldehyde	decreases expression	1
Ivermectin	decreases expression	1

Clinical trials (associated diseases)

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