TBC1D2

protein-coding

TBC1 domain family member 2, the group of MicroRNA protein coding host genes

Gene summary

Enables GTPase activator activity and cadherin binding activity. Involved in positive regulation of GTPase activity. Located in cell junction; cytoplasmic vesicle; and cytosol. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001267571.2

Inheritance

—

ClinVar variants

U:137B:22

Top phenotype

Mycotic Aneurysm, Intracranial

gnomAD constraint

pLI —, LoF o/e 0.55

Max pathogenic AF

—

Genomic locus

chr9:98,199,011-98,255,649

External References & Databases

Ensembl (ENSG00000095383)

Transcript & Mutation Effects

hg38 • Region Span ~56.6 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 TBC1D2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 137

not providedTotal: 11

Mycotic Aneurysm, IntracranialTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001267571.2. 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			1 clinvar		4 clinvar	5
missense			130 clinvar	14 clinvar	4 clinvar	148
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	137	14	8	159

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 35 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001267571.2	RefSeq	NP_001254500.1	13	MANE Select
ENST00000465784.7	Ensembl	ENSP00000481721.1	13	MANE Select
NM_001267572.1	RefSeq	NP_001254501.1	7	Standard
NM_001410988.1	RefSeq	NP_001397917.1	13	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
positive regulation of GTPase activity
activation of GTPase activity
regulation of cilium assembly

Molecular Function

GTPase activator activity
protein binding
Rab GTPase binding
cadherin binding

Cellular Component

nucleus
cytosol
cell junction
cytoplasmic vesicle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000375066
Coding exons: 13
Length: 56605
Individuals with no LoFs: 125588
Homozygous LoFs: 1
Heterozygous LoFs: 159
Defined: 125748
p: 0.000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.05	484	554	0.874	0.0000352	5911
Missense (PolyPhen)		143	189.91	0.75298		2155
Synonymous	1.84	204	240	0.849	0.0000149	1862
Loss of Function	2.63	22	39.9	0.551	0.00000190	440

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00068	0.00062	rare
Latino/Admixed American	0.00038	0.00035	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.0023	0.0023	notable
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00038	0.00031	rare
South Asian	0.0019	0.0018	notable
Other	0.00053	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acts as GTPase-activating protein for RAB7A. Signal effector acting as a linker between RAC1 and RAB7A, leading to RAB7A inactivation and subsequent inhibition of cadherin degradation and reduced cell-cell adhesion. {ECO:0000269|PubMed:20116244}.;

Recessive Scores

pRec: 0.102

Intolerance Scores

LoFtool: 0.886
RVIS EVS: 0.23
RVIS percentile EVS: 68.58

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.807

Gene Damage Prediction

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