TBC1D1

TBC1 domain family member 1

Basic information

Region (hg38): 4:37891083-38139175

Links

ENSG00000065882 ∙ NCBI:23216 ∙ OMIM:609850 ∙ HGNC:11578 ∙ Uniprot:Q86TI0 ∙ 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 TBC1D1 gene.

• Inborn genetic diseases (61 variants)
• not provided (16 variants)
• TBC1D1-related condition (7 variants)
• Non-syndromic renal or urinary tract malformation (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TBC1D1 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				6	3	9
missense			54	5	2	61
nonsense						0
start loss						0
frameshift			1	1		2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			10	1		11
Total	0	0	65	13	5

Variants in TBC1D1

This is a list of pathogenic ClinVar variants found in the TBC1D1 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-37902140-C-T		TBC1D1-related disorder	Benign/Likely benign (Feb 25, 2020)
4-37902157-T-A		TBC1D1-related disorder	Uncertain significance (Feb 14, 2024)
4-37902189-C-T		Inborn genetic diseases	Uncertain significance (Jul 12, 2022)
4-37902207-C-T		Inborn genetic diseases	Uncertain significance (Dec 17, 2021)
4-37902228-G-C		TBC1D1-related disorder	Uncertain significance (Feb 14, 2024)
4-37902238-G-A		TBC1D1-related disorder	Uncertain significance (Feb 22, 2024)
4-37902259-C-T		TBC1D1-related disorder	Likely benign (Jun 11, 2020)
4-37902297-G-A		Inborn genetic diseases	Uncertain significance (Oct 29, 2021)
4-37902302-A-G			Benign (Aug 03, 2017)
4-37902343-A-G			Likely benign (Mar 01, 2023)
4-37902351-G-C		Inborn genetic diseases	Uncertain significance (Mar 06, 2023)
4-37902351-G-T		Inborn genetic diseases	Uncertain significance (Nov 18, 2022)
4-37902370-G-C		Inborn genetic diseases	Uncertain significance (Mar 04, 2024)
4-37902458-C-T			Likely benign (Nov 01, 2023)
4-37902465-C-T		TBC1D1-related disorder	Uncertain significance (Oct 03, 2022)
4-37902468-C-T		TBC1D1-related disorder	Benign (Sep 17, 2019)
4-37902497-C-T		TBC1D1-related disorder	Likely benign (Jun 26, 2019)
4-37902508-C-T		Inborn genetic diseases	Uncertain significance (Nov 09, 2023)
4-37960475-C-G		not specified	Uncertain significance (Jun 05, 2023)
4-37960483-C-T		not specified	Uncertain significance (Jun 18, 2021)
4-37960484-G-A		not specified	Uncertain significance (Mar 31, 2022)
4-37960592-C-T		not specified	Uncertain significance (May 17, 2023)
4-37960612-A-G		not specified	Uncertain significance (Dec 05, 2022)
4-37960628-G-A		not specified	Uncertain significance (Dec 02, 2022)
4-37960695-C-A		not specified	Uncertain significance (Mar 13, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TBC1D1	protein_coding	protein_coding	ENST00000261439	19	248089

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.86e-13	1.00	125641	1	106	125748	0.000426

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.755	623	678	0.918	0.0000411	7685
Missense in Polyphen		205	240.33	0.853		2691
Synonymous	-0.0361	279	278	1.00	0.0000189	2229
Loss of Function	3.46	31	59.9	0.518	0.00000352	634

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00135	0.00135
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000772	0.000707
Finnish	0.0000929	0.0000924
European (Non-Finnish)	0.000437	0.000431
Middle Eastern	0.000772	0.000707
South Asian	0.000239	0.000196
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May act as a GTPase-activating protein for Rab family protein(s). May play a role in the cell cycle and differentiation of various tissues. Involved in the trafficking and translocation of GLUT4-containing vesicles and insulin-stimulated glucose uptake into cells (By similarity). {ECO:0000250}.
• Pathway: AMPK signaling pathway - Homo sapiens (human);Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Vesicle-mediated transport;Membrane Trafficking;Translocation of GLUT4 to the plasma membrane (Consensus)

Recessive Scores

• pRec: 0.206

Intolerance Scores

• loftool: 0.881
• rvis_EVS: 0.01
• rvis_percentile_EVS: 54.16

Haploinsufficiency Scores

• pHI: 0.163
• hipred: Y
• hipred_score: 0.554
• ghis: 0.456

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.615

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tbc1d1
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); normal phenotype

Gene ontology

• Biological process: intracellular protein transport;regulation of protein localization;membrane organization;activation of GTPase activity;regulation of cilium assembly
• Cellular component: nucleus;cytosol
• Molecular function: GTPase activator activity;protein binding;Rab GTPase binding