TBC1D5

TBC1 domain family member 5

Basic information

Region (hg38): 3:17157161-18444817

Links

ENSG00000131374 ∙ NCBI:9779 ∙ OMIM:615740 ∙ HGNC:19166 ∙ Uniprot:Q92609 ∙ 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 TBC1D5 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TBC1D5 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						0
missense			25	4		29
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	25	5	0

Variants in TBC1D5

This is a list of pathogenic ClinVar variants found in the TBC1D5 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-17160983-C-A		not specified	Uncertain significance (Mar 25, 2024)
3-17161013-C-T		not specified	Uncertain significance (Jul 27, 2021)
3-17161016-C-T		not specified	Uncertain significance (Jun 07, 2024)
3-17161214-C-T		not specified	Uncertain significance (Oct 06, 2022)
3-17161256-C-G		not specified	Uncertain significance (May 15, 2024)
3-17166810-C-G		not specified	Uncertain significance (Apr 09, 2024)
3-17166810-C-T		not specified	Uncertain significance (Oct 04, 2022)
3-17166849-G-T		TBC1D5-related disorder	Likely benign (Nov 19, 2022)
3-17166860-C-G		not specified	Uncertain significance (Aug 02, 2023)
3-17166874-C-T		not specified	Uncertain significance (Dec 20, 2023)
3-17166900-C-T		not specified	Uncertain significance (Mar 20, 2024)
3-17167786-T-C		not specified	Uncertain significance (Jan 04, 2024)
3-17185109-C-G		TBC1D5-related disorder	Likely benign (Mar 09, 2022)
3-17185114-T-C		not specified	Uncertain significance (Jan 30, 2024)
3-17185147-A-T		not specified	Uncertain significance (Oct 12, 2022)
3-17185180-A-G		not specified	Uncertain significance (Sep 15, 2021)
3-17214308-A-T		not specified	Uncertain significance (Feb 27, 2024)
3-17214335-C-T		not specified	Likely benign (Aug 04, 2022)
3-17214364-C-T		not specified	Uncertain significance (May 21, 2024)
3-17233704-C-G		not specified	Uncertain significance (May 06, 2022)
3-17233750-C-T		not specified	Uncertain significance (Aug 12, 2021)
3-17238178-C-T		not specified	Uncertain significance (Feb 27, 2023)
3-17238234-T-C		not specified	Uncertain significance (Nov 30, 2022)
3-17258593-T-TA		TBC1D5-related disorder	Likely benign (May 11, 2020)
3-17291911-A-G		not specified	Uncertain significance (Aug 10, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TBC1D5	protein_coding	protein_coding	ENST00000446818	21	1287656

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.64e-18	0.453	125641	0	107	125748	0.000426

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.687	383	423	0.906	0.0000210	5404
Missense in Polyphen		118	140.01	0.84278		1823
Synonymous	-0.296	158	153	1.03	0.00000816	1497
Loss of Function	1.74	34	46.9	0.725	0.00000250	549

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000381	0.000381
Ashkenazi Jewish	0.000401	0.000397
East Asian	0.000332	0.000326
Finnish	0.000234	0.000231
European (Non-Finnish)	0.000601	0.000571
Middle Eastern	0.000332	0.000326
South Asian	0.000445	0.000425
Other	0.000700	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May act as a GTPase-activating protein (GAP) for Rab family protein(s). May act as a GAP for RAB7A. Can displace RAB7A and retromer CSC subcomplex from the endosomal membrane to the cytosol; at least retromer displacement seems to require its catalytic activity (PubMed:19531583, PubMed:20923837). Required for retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN); the function seems to require its catalytic activity. Involved in regulation of autophagy (PubMed:22354992). May act as a molecular switch between endosomal and autophagosomal transport and is involved in reprogramming vesicle trafficking upon autophagy induction. Involved in the trafficking of ATG9A upon activation of autophagy. May regulate the recruitment of ATG9A-AP2-containing vesicles to autophagic membranes (PubMed:24603492). {ECO:0000269|PubMed:19531583, ECO:0000269|PubMed:20923837, ECO:0000269|PubMed:22354992, ECO:0000269|PubMed:24603492, ECO:0000305|PubMed:19531583, ECO:0000305|PubMed:22354992, ECO:0000305|PubMed:24603492}.

Recessive Scores

• pRec: 0.101

Intolerance Scores

• loftool: 0.962
• rvis_EVS: 0.09
• rvis_percentile_EVS: 60.65

Haploinsufficiency Scores

• pHI: 0.283
• hipred: N
• hipred_score: 0.443
• ghis: 0.583

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.943

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tbc1d5

Gene ontology

• Biological process: positive regulation of receptor internalization;intracellular protein transport;autophagy;macroautophagy;retrograde transport, endosome to Golgi;response to starvation;activation of GTPase activity;regulation of cilium assembly
• Cellular component: autophagosome;Golgi apparatus;cytosol;endosome membrane;AP-2 adaptor complex;retromer complex;intracellular membrane-bounded organelle;Atg1/ULK1 kinase complex
• Molecular function: GTPase activator activity;protein binding;Rab GTPase binding;AP-2 adaptor complex binding;retromer complex binding