TBC1D2B

protein-coding

TBC1 domain family member 2B

Gene summary

Predicted to enable GTPase activator activity. Involved in endocytosis. Located in cytosol and early endosome. Implicated in neurodevelopmental disorder with seizures and gingival overgrowth. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_144572.2

Inheritance

ClinVar variants

P:16U:157B:28

Top phenotype

Neurodevelopmental disorder with seizures and gingival overgrowth

gnomAD constraint

pLI —, LoF o/e 0.48

Max pathogenic AF

—

Genomic locus

chr15:77,984,036-78,077,724

External References & Databases

Ensembl (ENSG00000167202)

Transcript & Mutation Effects

hg38 • Region Span ~93.7 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorder with seizures and gingival overgrowthSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859148

Submitter: PanelApp Australia

neurodevelopmental disorder with seizures and gingival overgrowthSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859148

Submitter: Labcorp Genetics (formerly Invitae)

neurodevelopmental disorder with seizures and gingival overgrowthSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859148

Submitter: G2P

Clinical Genomic Database (CGD)

Neurodevelopmental disorder with seizures and gingival overgrowthAR

Manifestation: Craniofacial; Dental; Musculoskeletal; Neurologic; Ophthalmologic

Intervention: General

Rationale: 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

Refs: 32623794

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TBC1D2B variants in ClinVar

5 Conditions Cataloged

Inborn genetic diseasesTotal: 152

not providedTotal: 19

Neurodevelopmental disorder with seizures and gingival overgrowthTotal: 15

not specifiedTotal: 12

TBC1D2B-related disorderTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_144572.2. 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	17 clinvar		18
missense			153 clinvar	11 clinvar		164
nonsense	4 clinvar	6 clinvar	2 clinvar			12
start loss						0
frameshift	2 clinvar	4 clinvar	1 clinvar			7
splice donor/acceptor (+/-2bp)						0
Total	6	10	157	28	0	201

Highest pathogenic variant AF is 0.000011983654

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 38 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_144572.2	RefSeq	NP_653173.1	13	MANE Select
ENST00000300584.8	Ensembl	ENSP00000300584.3	13	MANE Select
NM_001387142.1	RefSeq	NP_001374071.1	14	Standard
NM_001387143.1	RefSeq	NP_001374072.1	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

intracellular protein transport
activation of GTPase activity
regulation of cilium assembly

Molecular Function

GTPase activator activity
protein binding
Rab GTPase binding

Cellular Component

cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000300584
Coding exons: 13
Length: 93689
Individuals with no LoFs: 125554
Homozygous LoFs: 0
Heterozygous LoFs: 39
Defined: 125593
p: 0.000155

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.82	388	503	0.772	0.0000283	6268
Missense (PolyPhen)		120	197.99	0.60609		2324
Synonymous	-0.174	205	202	1.02	0.0000117	1861
Loss of Function	3.09	20	41.5	0.482	0.00000208	523

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00021	0.00020	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00011	0.00011	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00017	0.00016	rare
South Asian	0.00016	0.00016	rare
Other	0.00034	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May act as a GTPase-activating protein. {ECO:0000250}.;

Recessive Scores

pRec: 0.110

Intolerance Scores

LoFtool: 0.972
RVIS EVS: 0.07
RVIS percentile EVS: 59.04

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.916

Gene Damage Prediction

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