TBC1D22A

protein-coding

TBC1 domain family member 22A

Gene summary

Enables 14-3-3 protein binding activity and protein homodimerization activity. Predicted to be active in Golgi apparatus. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

C22orf4

MANE transcript

NM_014346.5

Inheritance

—

ClinVar variants

U:76B:5

Top phenotype

Rare

gnomAD constraint

pLI —, LoF o/e 0.22

Max pathogenic AF

—

Genomic locus

chr22:46,762,617-47,175,699

External References & Databases

Ensembl (ENSG00000054611)

Transcript & Mutation Effects

hg38 • Region Span ~413.1 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 TBC1D22A variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 71

not providedTotal: 3

RareTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014346.5. 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	2 clinvar		4
missense			70 clinvar	1 clinvar	2 clinvar	73
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	76	3	2	81

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 61 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014346.5	RefSeq	NP_055161.1	13	MANE Select
ENST00000337137.9	Ensembl	ENSP00000336724.4	13	MANE Select
NM_001284303.2	RefSeq	NP_001271232.1	11	Standard
NM_001284304.2	RefSeq	NP_001271233.1	12	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
protein homodimerization activity
14-3-3 protein binding

Cellular Component

cell

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000337137
Coding exons: 13
Length: 412819
Individuals with no LoFs: 125733
Homozygous LoFs: 0
Heterozygous LoFs: 15
Defined: 125748
p: 0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.20	268	329	0.814	0.0000213	3410
Missense (PolyPhen)		92	147.73	0.62275		1571
Synonymous	-1.00	158	143	1.11	0.0000107	977
Loss of Function	3.76	6	27.1	0.221	0.00000126	307

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000055	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000062	0.000062	rare
South Asian	0.00017	0.00016	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May act as a GTPase-activating protein for Rab family protein(s). {ECO:0000250}.;

Recessive Scores

pRec: 0.0965

Intolerance Scores

LoFtool: 0.493
RVIS EVS: 0.2
RVIS percentile EVS: 67.43

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.868

Gene Damage Prediction

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