TBC1D10B

protein-coding

TBC1 domain family member 10B

Gene summary

Small G proteins of the RAB family (see MIM 179508) function in intracellular vesicle trafficking by switching from the GTP-bound state to the GDP-bound state with the assistance of guanine nucleotide exchange factors (GEFs; see MIM 609700) and GTPase-activating proteins (GAPs). TBC1D10B functions as a GAP for several proteins of the Rab family (Ishibashi et al., 2009 [PubMed 19077034]).[supplied by OMIM, Nov 2010]

MANE transcript

NM_015527.4

Inheritance

—

ClinVar variants

U:140B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.07

Max pathogenic AF

—

Genomic locus

chr16:30,357,102-30,370,494

External References & Databases

Ensembl (ENSG00000169221)

Transcript & Mutation Effects

hg38 • Region Span ~13.4 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 TBC1D10B variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 138

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015527.4. 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						0
missense			137 clinvar	2 clinvar		139
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	140	2	0	142

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 18 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015527.4	RefSeq	NP_056342.3	9	MANE Select
ENST00000409939.8	Ensembl	ENSP00000386538.3	9	MANE Select
ENST00000490703.1	Ensembl	ENSP00000456663.1	6	Standard
ENST00000936813.1	Ensembl	ENSP00000606872.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Vesicle-mediated transport
TBC/RABGAPs
Membrane Trafficking
Rab regulation of trafficking

Biological Process

intracellular protein transport
retrograde transport, endosome to Golgi
regulation of GTPase activity
activation of GTPase activity
regulation of cilium assembly

Molecular Function

GTPase activator activity
protein binding
Rab GTPase binding

Cellular Component

cytosol
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000409939
Coding exons: 9
Length: 13163
Individuals with no LoFs: 122214
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 122216
p: 0.00000818

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.95	288	397	0.725	0.0000256	4958
Missense (PolyPhen)		43	86.935	0.49462		938
Synonymous	0.858	148	162	0.914	0.00000930	1799
Loss of Function	4.69	2	29.5	0.0678	0.00000162	350

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00011	0.00010	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000093	0.0000091	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acts as GTPase-activating protein for RAB3A, RAB22A, RAB27A, AND RAB35. Does not act on RAB2A and RAB6A. {ECO:0000269|PubMed:16923811, ECO:0000269|PubMed:19077034}.;

Intolerance Scores

RVIS EVS: -0.03
RVIS percentile EVS: 51.92

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.798

Gene Damage Prediction

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