TIAM2

protein-coding

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

Gene summary

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. [provided by RefSeq, Jul 2008]

MANE transcript

NM_012454.4

Inheritance

—

ClinVar variants

U:254B:30

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.31

Max pathogenic AF

—

Genomic locus

chr6:154,832,697-155,257,723

External References & Databases

Ensembl (ENSG00000146426)

Transcript & Mutation Effects

hg38 • Region Span ~425.0 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 TIAM2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 257

not providedTotal: 22

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012454.4. 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	5 clinvar	4 clinvar	12
missense			248 clinvar	16 clinvar	5 clinvar	269
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	254	21	9	284

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 32 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012454.4	RefSeq	NP_036586.3	24	MANE Select
ENST00000682666.1	Ensembl	ENSP00000507157.1	24	MANE Select
NM_001010927.3	RefSeq	NP_001010927.2	12	Standard
NM_001384546.1	RefSeq	NP_001371475.1	24	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)
Chemokine signaling pathway
Signaling by GPCR
Signal Transduction
Rho GTPase cycle

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

Molecular Function

guanyl-nucleotide exchange factor activity
Rho guanyl-nucleotide exchange factor activity
GTPase activator activity

Cellular Component

cytosol
membrane
lamellipodium
filopodium
growth cone

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000461783
Coding exons: 24
Length: 425027
Individuals with no LoFs: 122463
Homozygous LoFs: 75
Heterozygous LoFs: 3210
Defined: 125748
p: 0.0131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.24	851	960	0.887	0.0000566	11175
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.050	0.050	notable
Latino/Admixed American	0.0067	0.0067	notable
Ashkenazi Jewish	0.0065	0.0065	notable
East Asian	0.00056	0.00054	rare
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.0059	0.0058	notable
South Asian	0.050	0.050	notable
Other	0.0080	0.0078	notable

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.134

Intolerance Scores

LoFtool: 0.807
RVIS EVS: -0.28
RVIS percentile EVS: 33.54

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.170

Gene Damage Prediction

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