TBC1D8

protein-coding

TBC1 domain family member 8, the group of GRAM domain containing

Gene summary

Predicted to enable GTPase activator activity. Predicted to be involved in blood circulation and positive regulation of cell population proliferation. Predicted to be located in membrane. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001330348.2

Inheritance

—

ClinVar variants

U:178B:11

Top phenotype

RPL31-related condition

gnomAD constraint

pLI —, LoF o/e 0.51

Max pathogenic AF

—

Genomic locus

chr2:101,007,228-101,252,866

External References & Databases

Ensembl (ENSG00000204634)

Transcript & Mutation Effects

hg38 • Region Span ~245.6 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 TBC1D8 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 174

not providedTotal: 11

RPL31-related conditionTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001330348.2. 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			2 clinvar	1 clinvar	3 clinvar	6
missense			173 clinvar	7 clinvar		180
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	178	8	3	189

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 70 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001330348.2	RefSeq	NP_001317277.1	20	MANE Select
ENST00000409318.2	Ensembl	ENSP00000386856.1	20	MANE Select
NM_001102426.3	RefSeq	NP_001095896.1	20	Standard
ENST00000376840.8	Ensembl	ENSP00000366036.4	20	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cell Cycle

Biological Process

intracellular protein transport
blood circulation
positive regulation of cell population proliferation
activation of GTPase activity
regulation of cilium assembly

Molecular Function

GTPase activator activity
Rab GTPase binding

Cellular Component

cell
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000376840
Coding exons: 20
Length: 245250
Individuals with no LoFs: 125210
Homozygous LoFs: 0
Heterozygous LoFs: 97
Defined: 125307
p: 0.000387

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.39	553	653	0.847	0.0000392	7531
Missense (PolyPhen)		191	259.44	0.73619		2926
Synonymous	0.186	281	285	0.986	0.0000196	2155
Loss of Function	3.44	30	58.4	0.514	0.00000349	619

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00061	0.00057	rare
Latino/Admixed American	0.00036	0.00035	rare
Ashkenazi Jewish	0.00040	0.00040	rare
East Asian	0.00028	0.00027	rare
Finnish	0.00033	0.00032	rare
European (Non-Finnish)	0.00044	0.00043	rare
South Asian	0.00023	0.00023	rare
Other	0.00067	0.00066	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May act as a GTPase-activating protein for Rab family protein(s).;

Recessive Scores

pRec: 0.130

Intolerance Scores

LoFtool: 0.525
RVIS EVS: -1.01
RVIS percentile EVS: 8.21

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.281

Gene Damage Prediction

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