TBC1D21

protein-coding

TBC1 domain family member 21

Gene summary

Enables GTPase activator activity and small GTPase binding activity. Predicted to be involved in plasma membrane to endosome transport; sperm axoneme assembly; and sperm mitochondrial sheath assembly. Located in extracellular exosome. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_153356.3

Inheritance

—

ClinVar variants

U:45B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.67

Max pathogenic AF

—

Genomic locus

chr15:73,873,564-73,889,214

External References & Databases

Ensembl (ENSG00000167139)

Transcript & Mutation Effects

hg38 • Region Span ~15.7 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 TBC1D21 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 47

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_153356.3. 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				1 clinvar		1
missense			45 clinvar	1 clinvar		46
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	45	2	0	47

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_153356.3	RefSeq	NP_699187.1	11	MANE Select
ENST00000300504.7	Ensembl	ENSP00000300504.2	11	MANE Select
NM_001286434.2	RefSeq	NP_001273363.1	10	Standard
ENST00000535547.6	Ensembl	ENSP00000439325.2	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

intracellular protein transport
spermatogenesis
cell differentiation
activation of GTPase activity
regulation of cilium assembly

Molecular Function

actin binding
GTPase activator activity
Rab GTPase binding

Cellular Component

acrosomal vesicle
cytoskeleton
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000300504
Coding exons: 11
Length: 15607
Individuals with no LoFs: 125714
Homozygous LoFs: 0
Heterozygous LoFs: 34
Defined: 125748
p: 0.000135

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.486	175	194	0.902	0.0000109	2252
Missense (PolyPhen)		55	65.827	0.83553		822
Synonymous	0.456	71	76.1	0.934	0.00000460	578
Loss of Function	1.36	13	19.5	0.667	8.31e-7	220

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00074	0.00074	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00011	0.000088	rare
South Asian	0.000098	0.000098	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May act as a GTPase-activating protein for Rab family protein(s) (PubMed:19077034). May be involved in acrosome formation and cytoskeletal reorganization during spermiogenesis, possibly by regulating RAB3A activity (PubMed:21128978). {ECO:0000305|PubMed:19077034, ECO:0000305|PubMed:21128978}.;

Intolerance Scores

LoFtool: 0.689
RVIS EVS: -0.14
RVIS percentile EVS: 43.77

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0222

Gene Damage Prediction

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