TBC1D8B

TBC1 domain family member 8B, the group of EF-hand domain containing|GRAM domain containing

Basic information

Region (hg38): X:106802673-106876150

Links

ENSG00000133138 ∙ NCBI:54885 ∙ OMIM:301027 ∙ HGNC:24715 ∙ Uniprot:Q0IIM8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• familial idiopathic steroid-resistant nephrotic syndrome (Supportive), mode of inheritance: AD
• nephrotic syndrome, type 20 (Limited), mode of inheritance: XL
• nephrotic syndrome, type 20 (Strong), mode of inheritance: XL
• nephrotic syndrome, type 20 (Moderate), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Nephrotic syndrome, type 20	XL	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Renal	30661770
Renal transplant has been described

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TBC1D8B gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TBC1D8B 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				16	4	20
missense		2	85	10	1	98
nonsense		1	2			3
start loss						0
frameshift			2	1		3
inframe indel			1			1
splice donor/acceptor (+/-2bp)			1			1
splice region			2	3	2	7
non coding				8	14	22
Total	0	3	91	35	19

Variants in TBC1D8B

This is a list of pathogenic ClinVar variants found in the TBC1D8B region.

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

Position	Type	Phenotype	Significance	ClinVar
X-106802873-A-G		Nephrotic syndrome, type 20	Uncertain significance (Sep 24, 2021)
X-106802952-C-T			Likely benign (Nov 01, 2022)
X-106802956-G-C		not specified	Uncertain significance (Feb 17, 2023)
X-106802955-C-CGGG			Uncertain significance (Oct 14, 2023)
X-106802972-G-A		TBC1D8B-related disorder	Uncertain significance (Apr 10, 2023)
X-106818560-A-G			Benign (May 25, 2021)
X-106818656-A-G		TBC1D8B-related disorder	Benign (Jan 13, 2024)
X-106818694-G-A			Benign (Jan 28, 2024)
X-106818695-G-A		Nephrotic syndrome, type 20	Uncertain significance (Mar 04, 2021)
X-106818708-A-C		not specified	Uncertain significance (May 04, 2023)
X-106818722-C-T		Nephrotic syndrome, type 20	Pathogenic (Aug 30, 2023)
X-106818723-G-A		not specified	Uncertain significance (Jan 17, 2024)
X-106818756-A-C		not specified	Uncertain significance (Sep 22, 2023)
X-106818757-C-T			Likely benign (Dec 21, 2023)
X-106818945-GT-G			Benign (May 25, 2021)
X-106820871-A-C		TBC1D8B-related disorder	Likely benign (Jan 10, 2023)
X-106820880-C-A		Nephrotic syndrome, type 20	Uncertain significance (-)
X-106820923-A-C		not specified	Uncertain significance (Dec 21, 2023)
X-106821006-C-T			Likely benign (Nov 15, 2023)
X-106821115-C-T			Benign (May 22, 2021)
X-106822026-C-G		not specified	Uncertain significance (Jan 03, 2024)
X-106822037-C-T		Nephrotic syndrome, type 20	Likely pathogenic (Mar 16, 2023)
X-106822043-G-A		TBC1D8B-related disorder	Uncertain significance (Jul 14, 2022)
X-106822128-G-A			Uncertain significance (Oct 06, 2022)
X-106822144-T-C			Uncertain significance (-)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TBC1D8B	protein_coding	protein_coding	ENST00000357242	21	73466

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.95e-9	0.998	125646	27	70	125743	0.000386

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0570	372	375	0.992	0.0000261	7389
Missense in Polyphen		125	128.99	0.96907		2410
Synonymous	0.838	118	130	0.907	0.00000867	2028
Loss of Function	2.83	20	39.1	0.511	0.00000291	755

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00127	0.00118
Ashkenazi Jewish	0.000690	0.000496
East Asian	0.00234	0.00174
Finnish	0.00	0.00
European (Non-Finnish)	0.000291	0.000202
Middle Eastern	0.00234	0.00174
South Asian	0.000575	0.000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May act as a GTPase-activating protein for Rab family protein(s).
• Pathway: Golgi Associated Vesicle Biogenesis;Clathrin derived vesicle budding;trans-Golgi Network Vesicle Budding;Vesicle-mediated transport;Membrane Trafficking (Consensus)

Intolerance Scores

• loftool: 0.645
• rvis_EVS: -1.15
• rvis_percentile_EVS: 6.32

Haploinsufficiency Scores

• pHI: 0.230
• hipred: Y
• hipred_score: 0.544
• ghis: 0.541

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.244

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tbc1d8b

Gene ontology

• Biological process: intracellular protein transport;activation of GTPase activity
• Cellular component: cell
• Molecular function: GTPase activator activity;calcium ion binding;Rab GTPase binding