TBC1D23

TBC1 domain family member 23

Basic information

Region (hg38): 3:100260992-100325251

Links

ENSG00000036054 ∙ NCBI:55773 ∙ OMIM:617687 ∙ HGNC:25622 ∙ Uniprot:Q9NUY8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pontocerebellar hypoplasia, type 11 (Strong), mode of inheritance: AR
• pontocerebellar hypoplasia, type 11 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pontocerebellar hypoplasia, type 11	AR	General	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	Neurologic	28823706; 28823707

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TBC1D23 gene.

• Inborn_genetic_diseases (80 variants)
• Pontocerebellar_hypoplasia,_type_11 (22 variants)
• not_provided (21 variants)
• TBC1D23-related_disorder (11 variants)
• not_specified (3 variants)
• Pontoneocerebellar_hypoplasia (3 variants)
• HP:0000750%3B_HP:0001263 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TBC1D23 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001199198.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	7	4	12
missense	1		87	2	1	91
nonsense		1	1			2
start loss						0
frameshift	3	5				8
splice donor/acceptor (+/-2bp)	4	1				5
Total	8	7	89	9	5

Highest pathogenic variant AF is 0.0000061976993

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TBC1D23	protein_coding	protein_coding	ENST00000394144	19	64252

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000178	1.00	125711	0	37	125748	0.000147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.89	258	359	0.719	0.0000175	4608
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000386	0.000386
Ashkenazi Jewish	0.00	0.00
East Asian	0.000219	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.000143	0.000141
Middle Eastern	0.000219	0.000217
South Asian	0.000191	0.000163
Other	0.000328	0.000326

dbNSFP

Source: dbNSFP

• 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

Haploinsufficiency Scores

• pHI: 0.289
• hipred: N
• hipred_score: 0.478
• ghis: 0.599

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.154

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tbc1d23
• Phenotype: immune system phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: tbc1d23
• Affected structure: brainstem
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: brain development;vesicle-mediated transport;neuron projection development;regulation of tumor necrosis factor production;positive regulation of interleukin-6 production;retrograde transport, endosome to Golgi;regulation of inflammatory response;vesicle tethering to Golgi;embryonic brain development
• Cellular component: Golgi apparatus;trans-Golgi network;cytosol;cytoplasmic vesicle;WASH complex
• Molecular function: protein binding