TIAM1

TIAM Rac1 associated GEF 1, the group of Dbl family Rho GEFs|PDZ domain containing|Pleckstrin homology domain containing

Basic information

Region (hg38): 21:31118415-31559977

Links

ENSG00000156299 ∙ NCBI:7074 ∙ OMIM:600687 ∙ HGNC:11805 ∙ Uniprot:Q13009 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with language delay and seizures (Limited), mode of inheritance: AR
• neurodevelopmental disorder with language delay and seizures (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with language delay and seizures	AR	Endocrine	Among other findings, individuals have been described with endocrine disorders such as hypothyroidism, and awareness may allow medical management	Craniofacial; Endocrine; Neurologic	35240055

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TIAM1 gene.

• Inborn genetic diseases (59 variants)
• not provided (16 variants)
• TIAM1-related condition (2 variants)
• Neurodevelopmental disorder with language delay and seizures (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TIAM1 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				2	1	3
missense			65	1	2	68
nonsense						0
start loss						0
frameshift			2			2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	0	67	3	4

Variants in TIAM1

This is a list of pathogenic ClinVar variants found in the TIAM1 region.

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

Position	Type	Phenotype	Significance	ClinVar
21-31120439-C-T		TIAM1-related disorder	Likely benign (Jul 18, 2022)
21-31120504-G-A		not specified	Uncertain significance (Jun 30, 2022)
21-31120504-G-T		Neurodevelopmental disorder with language delay and seizures	Pathogenic (Jun 14, 2022)
21-31120562-G-T		not specified	Uncertain significance (Jun 29, 2023)
21-31120564-C-T		not specified	Likely benign (Feb 10, 2022)
21-31120601-C-T		not specified	Uncertain significance (Aug 04, 2021)
21-31120622-C-T		not specified	Uncertain significance (Jun 23, 2021)
21-31120700-G-C		not specified	Uncertain significance (Jan 23, 2024)
21-31120713-A-G		TIAM1-related disorder	Benign (Jun 20, 2023)
21-31120718-C-CG		TIAM1-related disorder	Uncertain significance (May 10, 2023)
21-31120738-T-C		TIAM1-related disorder	Benign (Mar 04, 2019)
21-31120744-G-A		not specified	Uncertain significance (Oct 13, 2021)
21-31120760-C-T		not specified	Likely benign (Nov 03, 2023)
21-31120785-G-A			Likely benign (Apr 09, 2018)
21-31120789-C-T		not specified	Uncertain significance (May 11, 2022)
21-31124502-C-T			Benign (Oct 01, 2023)
21-31124529-G-C		not specified	Uncertain significance (Oct 05, 2023)
21-31124537-C-G		not specified	Uncertain significance (Jun 08, 2022)
21-31124538-C-T		TIAM1-related disorder	Likely benign (Dec 30, 2019)
21-31124539-G-A		not specified	Uncertain significance (Jan 16, 2024)
21-31124646-C-T		TIAM1-related disorder	Benign (Oct 28, 2019)
21-31127155-A-G		TIAM1-related disorder	Benign (Oct 17, 2019)
21-31130216-C-T		not specified	Uncertain significance (Sep 14, 2023)
21-31130242-G-A		Neurodevelopmental disorder with language delay and seizures	Pathogenic (Jun 14, 2022)
21-31130263-C-T		not specified	Uncertain significance (Mar 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TIAM1	protein_coding	protein_coding	ENST00000286827	25	441557

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.957	0.0434	125714	0	34	125748	0.000135

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.70	801	948	0.845	0.0000591	10487
Missense in Polyphen		179	250.82	0.71365		2785
Synonymous	-0.595	417	402	1.04	0.0000287	3120
Loss of Function	6.48	15	76.0	0.197	0.00000426	838

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000298	0.000297
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.0000549	0.0000544
Finnish	0.000324	0.000323
European (Non-Finnish)	0.000123	0.000123
Middle Eastern	0.0000549	0.0000544
South Asian	0.0000980	0.0000980
Other	0.00	0.00

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. Activates RAC1, CDC42, and to a lesser extent RHOA. Required for normal cell adhesion and cell migration. {ECO:0000269|PubMed:20361982}.
• Pathway: Tight junction - Homo sapiens (human);Chemokine signaling pathway - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Regulation of Microtubule Cytoskeleton;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Chemokine signaling pathway;Ebola Virus Pathway on Host;Ebola Virus Pathway on Host;Ras Signaling;Developmental Biology;Signaling by GPCR;Signal Transduction;EPH-Ephrin signaling;EPHB-mediated forward signaling;EPH-ephrin mediated repulsion of cells;Rho GTPase cycle;Signaling by Rho GTPases;Activated NTRK2 signals through CDK5;Signaling by NTRK2 (TRKB);Signaling by NTRKs;Regulation of RAC1 activity;NRAGE signals death through JNK;Posttranslational regulation of adherens junction stability and dissassembly;Death Receptor Signalling;p75 NTR receptor-mediated signalling;Ephrin B reverse signaling;Axon guidance;G alpha (12/13) signalling events;Signaling by Receptor Tyrosine Kinases;GPCR downstream signalling;Neurotrophic factor-mediated Trk receptor signaling;LPA receptor mediated events;CDC42 signaling events;Cell death signalling via NRAGE, NRIF and NADE;Arf6 downstream pathway;EPHA2 forward signaling;E-cadherin signaling in the nascent adherens junction (Consensus)

Recessive Scores

• pRec: 0.333

Intolerance Scores

• loftool: 0.421
• rvis_EVS: -0.91
• rvis_percentile_EVS: 9.84

Haploinsufficiency Scores

• pHI: 0.481
• hipred: Y
• hipred_score: 0.790
• ghis: 0.557

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.737

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tiam1
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); neoplasm

Gene ontology

• Biological process: cardiac muscle hypertrophy;apoptotic process;cell-matrix adhesion;G protein-coupled receptor signaling pathway;positive regulation of cell population proliferation;regulation of epithelial to mesenchymal transition;positive regulation of epithelial to mesenchymal transition;cell migration;Rac protein signal transduction;positive regulation of cell migration;positive regulation of protein binding;regulation of Rho protein signal transduction;response to cocaine;positive regulation of apoptotic process;positive regulation of JUN kinase activity;ephrin receptor signaling pathway;positive regulation of axonogenesis;regulation of small GTPase mediated signal transduction;Wnt signaling pathway, planar cell polarity pathway;positive regulation of dendritic spine morphogenesis;regulation of insulin secretion involved in cellular response to glucose stimulus;regulation of ERK1 and ERK2 cascade;protein localization to membrane;activation of GTPase activity;NMDA selective glutamate receptor signaling pathway;positive regulation of Schwann cell chemotaxis;regulation of dopaminergic neuron differentiation;regulation of modification of postsynaptic actin cytoskeleton;neuron projection extension;regulation of non-canonical Wnt signaling pathway
• Cellular component: nucleus;cytosol;microtubule;plasma membrane;cell-cell junction;extrinsic component of cytoplasmic side of plasma membrane;ruffle membrane;neuronal cell body;dendritic spine;cell-cell contact zone;axonal growth cone;main axon;glutamatergic synapse;extrinsic component of postsynaptic density membrane
• Molecular function: guanyl-nucleotide exchange factor activity;Rho guanyl-nucleotide exchange factor activity;protein binding;microtubule binding;lipid binding;kinase binding;Rac guanyl-nucleotide exchange factor activity;receptor tyrosine kinase binding