TBC1D23
protein-codingTBC1 domain family member 23
Gene summary
Involved in brain development; retrograde transport, endosome to Golgi; and vesicle tethering to Golgi. Located in WASH complex; cytoplasmic vesicle; and trans-Golgi network. Implicated in pontocerebellar hypoplasia type 11. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~64.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0054669
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0054669
Submitter: G2P
Clinical Genomic Database (CGD)
Manifestation: Neurologic
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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TBC1D23 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001199198.3. 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 | 3 | 10 | 3 | 16 | ||
| missense | 91 | 6 | 1 | 98 | ||
| nonsense | 1 | 2 | 1 | 4 | ||
| start loss | 0 | |||||
| frameshift | 4 | 7 | 11 | |||
| splice donor/acceptor (+/-2bp) | 4 | 1 | 4 | 9 | ||
| Total | 9 | 10 | 99 | 16 | 4 | 138 |
Highest pathogenic variant AF is 0.0001480149
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001186127.1 | 19 | MANE Select | |
| Ensembl | ENSP00000377700.4 | 19 | MANE Select | |
| RefSeq | NP_060779.2 | 18 | Standard | |
| Ensembl | ENSP00000340693.5 | 18 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| tbc1d23 | Danio rerio | Structure: brainstem Quality: decreased size abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- brain development
- vesicle-mediated transport
- neuron projection development
- regulation of tumor necrosis factor production
- positive regulation of interleukin-6 production
Molecular Function
- protein binding
Cellular Component
- Golgi apparatus
- trans-Golgi network
- cytosol
- cytoplasmic vesicle
- WASH complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000394144
- Coding exons
- 19
- Length
- 64252
- Individuals with no LoFs
- 125711
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 37
- Defined
- 125748
- p
- 0.000147
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.89 | 258 | 359 | 0.719 | 0.0000175 | 4608 |
| Missense (PolyPhen) | 53 | 82.984 | 0.63868 | 1057 | ||
| Synonymous | 0.787 | 115 | 126 | 0.911 | 0.00000643 | 1262 |
| Loss of Function | 3.50 | 15 | 38.5 | 0.390 | 0.00000176 | 511 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.00026 | 0.00023 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00014 | 0.00014 | rare |
| South Asian | 0.00019 | 0.00016 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Putative Rab GTPase-activating protein which plays a role in vesicular trafficking (PubMed:28823707). Involved in endosome-to-Golgi trafficking. Acts as a bridging protein by binding simultaneously to golgins, including GOLGA1 and GOLGA4, located at the trans-Golgi, and to the WASH complex, located on endosome-derived vesicles (PubMed:29084197, PubMed:29426865). Together with WDR11 complex facilitates the golgin-mediated capture of vesicles generated using AP-1 (PubMed:29426865). Plays a role in brain development, including in cortical neuron positioning (By similarity). May also be important for neurite outgrowth, possibly through its involvement in membrane trafficking and cargo delivery, 2 processes that are essential for axonal and dendritic growth (By similarity). May act as a general inhibitor of innate immunity signaling, strongly inhibiting multiple TLR and dectin/CLEC7A-signaling pathways. Does not alter initial activation events, but instead affects maintenance of inflammatory gene expression several hours after bacterial lipopolysaccharide (LPS) challenge (By similarity). {ECO:0000250|UniProtKB:Q8K0F1, ECO:0000269|PubMed:28823707, ECO:0000269|PubMed:29084197, ECO:0000269|PubMed:29426865}.;
Intolerance Scores
- LoFtool
- 0.797
- RVIS EVS
- -0.8
- RVIS percentile EVS
- 12.46
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.154
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |