TIAM2

TIAM Rac1 associated GEF 2, the group of Pleckstrin homology domain containing|PDZ domain containing|Dbl family Rho GEFs

Basic information

Region (hg38): 6:154832696-155257723

Links

ENSG00000146426 ∙ NCBI:26230 ∙ OMIM:604709 ∙ HGNC:11806 ∙ Uniprot:Q8IVF5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TIAM2 gene.

• Inborn genetic diseases (68 variants)
• not provided (19 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TIAM2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				5	3	8
missense			63	7	7	77
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding					1	1
Total	0	0	63	12	11

Variants in TIAM2

This is a list of pathogenic ClinVar variants found in the TIAM2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-154832730-C-G		not specified	Uncertain significance (Dec 19, 2022)
6-154832730-C-T		not specified	Uncertain significance (Sep 26, 2023)
6-154832751-G-A		not specified	Uncertain significance (Jan 20, 2023)
6-154832777-TATAAG-T		Autism spectrum disorder	Likely benign (Apr 13, 2022)
6-154832811-C-G		not specified	Uncertain significance (Oct 10, 2023)
6-154832820-C-G		not specified	Uncertain significance (Dec 15, 2023)
6-154832973-C-A		not specified	Uncertain significance (Feb 14, 2023)
6-154832982-G-A		not specified	Uncertain significance (Mar 22, 2023)
6-154833016-A-G		not specified	Uncertain significance (May 16, 2023)
6-154833034-G-A		not specified	Uncertain significance (Feb 22, 2023)
6-154833139-G-C		not specified	Uncertain significance (Oct 24, 2023)
6-154833243-C-T		not specified	Uncertain significance (Aug 11, 2022)
6-154833251-G-T		not specified	Uncertain significance (Aug 16, 2021)
6-154833252-C-T		not specified	Uncertain significance (Mar 01, 2024)
6-154833348-A-C		not specified	Uncertain significance (Sep 25, 2023)
6-155129244-G-C			Benign (Aug 20, 2018)
6-155129249-C-T		not specified	Uncertain significance (Sep 29, 2023)
6-155129260-T-C		not specified	Uncertain significance (Feb 13, 2024)
6-155129320-C-T		not specified	Uncertain significance (Oct 04, 2022)
6-155129436-C-G		not specified	Uncertain significance (Aug 22, 2023)
6-155129564-A-G		not specified	Uncertain significance (Nov 07, 2022)
6-155129585-A-C		not specified	Uncertain significance (Dec 18, 2023)
6-155129638-A-C		not specified	Uncertain significance (May 08, 2023)
6-155129638-A-G		not specified	Uncertain significance (Aug 12, 2022)
6-155129690-G-T		not specified	Uncertain significance (Jan 17, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TIAM2	protein_coding	protein_coding	ENST00000461783	24	425027

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000324	1.00	122463	75	3210	125748	0.0131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.24	851	960	0.887	0.0000566	11175
Missense in Polyphen		168	235.97	0.71196		2765
Synonymous	-1.12	432	403	1.07	0.0000263	3351
Loss of Function	5.59	23	75.3	0.305	0.00000419	864

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0567	0.0562
Ashkenazi Jewish	0.00646	0.00647
East Asian	0.000556	0.000544
Finnish	0.000231	0.000231
European (Non-Finnish)	0.00590	0.00584
Middle Eastern	0.000556	0.000544
South Asian	0.0500	0.0495
Other	0.00800	0.00785

dbNSFP

Source: dbNSFP

• Function: 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 (By similarity). Activates specifically RAC1, but not CDC42 and RHOA. {ECO:0000250, ECO:0000269|PubMed:10512681}.
• Pathway: Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha);Chemokine signaling pathway;Signaling by GPCR;Signal Transduction;Rho GTPase cycle;Signaling by Rho GTPases;Regulation of RAC1 activity;NRAGE signals death through JNK;Death Receptor Signalling;p75 NTR receptor-mediated signalling;G alpha (12/13) signalling events;GPCR downstream signalling;Cell death signalling via NRAGE, NRIF and NADE (Consensus)

Recessive Scores

• pRec: 0.134

Intolerance Scores

• loftool: 0.807
• rvis_EVS: -0.28
• rvis_percentile_EVS: 33.54

Haploinsufficiency Scores

• pHI: 0.186
• hipred: Y
• hipred_score: 0.628
• ghis: 0.485

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.170

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Tiam2

Gene ontology

• Biological process: G protein-coupled receptor signaling pathway;regulation of lipid metabolic process;regulation of Rho protein signal transduction;intracellular signal transduction;positive regulation of apoptotic process;positive regulation of GTPase activity;regulation of small GTPase mediated signal transduction
• Cellular component: cytosol;membrane;lamellipodium;filopodium;growth cone;extracellular exosome
• Molecular function: guanyl-nucleotide exchange factor activity;Rho guanyl-nucleotide exchange factor activity;GTPase activator activity