TBC1D15

protein-coding

TBC1 domain family member 15

Gene summary

This gene encodes a member of the Ras-like proteins in brain-GTPase activating protein superfamily that share a conserved Tre-2/Bub2/Cdc16 domain. The encoded protein interacts with Ras-like protein in brain 5A and may function as a regulator of intracellular trafficking. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Apr 2009]

MANE transcript

NM_001146213.3

Inheritance

—

ClinVar variants

U:83B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.26

Max pathogenic AF

—

Genomic locus

chr12:71,839,707-71,927,248

External References & Databases

Ensembl (ENSG00000121749)

Transcript & Mutation Effects

hg38 • Region Span ~87.5 kb

Loading mutation effect viewer...

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 TBC1D15 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 72

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001146213.3. 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			3 clinvar			3
missense			74 clinvar	3 clinvar		77
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	83	3	0	86

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 58 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001146213.3	RefSeq	NP_001139685.2	17	MANE Select
ENST00000485960.7	Ensembl	ENSP00000420678.2	17	MANE Select
NM_001146214.3	RefSeq	NP_001139686.2	14	Standard
NM_001385848.1	RefSeq	NP_001372777.1	17	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Mitophagy - animal - Homo sapiens (human)
Vesicle-mediated transport
TBC/RABGAPs
Membrane Trafficking
Rab regulation of trafficking

Biological Process

intracellular protein transport
regulation of GTPase activity
activation of GTPase activity
regulation of cilium assembly

Molecular Function

GTPase activator activity
protein binding
Rab GTPase binding

Cellular Component

extracellular region
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000550746
Coding exons: 18
Length: 87143
Individuals with no LoFs: 125722
Homozygous LoFs: 0
Heterozygous LoFs: 26
Defined: 125748
p: 0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.917	304	352	0.863	0.0000169	4583
Missense (PolyPhen)		106	147.67	0.71782		2055
Synonymous	-1.89	148	122	1.22	0.00000631	1202
Loss of Function	4.50	11	42.8	0.257	0.00000213	533

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00018	0.00016	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.000098	0.000098	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acts as a GTPase activating protein for RAB7A. Does not act on RAB4, RAB5 or RAB6 (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.0955

Intolerance Scores

LoFtool: 0.710
RVIS EVS: -0.89
RVIS percentile EVS: 10.43

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): K
Indispensability pred.: E
Indispensability score: 0.853

Gene Damage Prediction

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