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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
TBC1D23
TBC1 domain family member 23
Chromosome 3 Β· 3q12.1-q12.2
NCBI Gene: 55773Ensembl: ENSG00000036054.14HGNC: HGNC:25622UniProt: Q9NUY8
42PubMed Papers
21Diseases
0Drugs
14Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
Golgi apparatusprotein bindingcytoplasmic vesiclebrain developmentNon-syndromic pontocerebellar hypoplasiapontocerebellar hypoplasiagenetic disorderIntellectual disability
✦AI Summary

TBC1D23 is a putative Rab GTPase-activating protein that serves as a critical regulator of endosome-to-Golgi trafficking 1. The protein functions as a bridging factor, simultaneously binding to trans-Golgi golgins (including GOLGA1 and GOLGA4) and the WASH complex on endosome-derived vesicles, facilitating vesicle capture and trafficking 2. Structurally, TBC1D23's C-terminal domain adopts a pleckstrin homology fold that selectively binds phosphatidylinositol 4-phosphate (PtdIns(4)P) while interacting with FAM21 on the opposite surface 2. The protein forms a direct complex with FAM91A1, cooperating to regulate endosomal trafficking of KIAA0319L, which is important for axonal growth 3. TBC1D23 also plays a role in STING-mediated innate immunity by regulating TBK1 trafficking from endosomes to the trans-Golgi network, affecting interferon production and antitumor immune responses 4. Homozygous mutations in TBC1D23 cause pontocerebellar hypoplasia type 11 (PCH11), a non-degenerative neurological disorder characterized by microcephaly, cerebellar and pontine hypoplasia, developmental delay, and ataxia 1. The protein's essential role in vesicular trafficking makes it critical for proper brain development and neuronal function.

Sources cited
1
TBC1D23 is a putative Rab GTPase-activating protein and mutations cause pontocerebellar hypoplasia type 11
PMID: 28823706
2
TBC1D23 C-terminal domain structure, phosphoinositide binding, and FAM21 interaction
PMID: 31624125
3
TBC1D23 forms complex with FAM91A1 and regulates trafficking of KIAA0319L
PMID: 37903274
4
TBC1D23 role in STING signaling and antitumor immunity through TBK1 trafficking
PMID: 41748771
⚠Limited data available β€” This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsβ“˜21
Non-syndromic pontocerebellar hypoplasiaOpen Targets
0.75Strong
pontocerebellar hypoplasiaOpen Targets
0.46Moderate
genetic disorderOpen Targets
0.41Moderate
Intellectual disabilityOpen Targets
0.37Weak
neurodegenerative diseaseOpen Targets
0.34Weak
glaucomaOpen Targets
0.12Weak
non-small cell lung carcinomaOpen Targets
0.07Suggestive
anemia (phenotype)Open Targets
0.02Suggestive
Hallux valgusOpen Targets
0.02Suggestive
neoplasmOpen Targets
0.02Suggestive
orofacial cleftOpen Targets
0.02Suggestive
Abnormality of the skeletal systemOpen Targets
0.02Suggestive
cryopyrin-associated periodic syndromeOpen Targets
0.01Suggestive
insulinomaOpen Targets
0.01Suggestive
pancreatic ductal adenocarcinomaOpen Targets
0.01Suggestive
melanomaOpen Targets
0.00Suggestive
cutaneous melanomaOpen Targets
0.00Suggestive
lymph node metastatic carcinomaOpen Targets
0.00Suggestive
Rett syndromeOpen Targets
0.00Suggestive
syphilisOpen Targets
0.00Suggestive
Pontocerebellar hypoplasia 11UniProt
Pathogenic Variants14
NM_001199198.3(TBC1D23):c.951_954del (p.Cys317fs)Pathogenic
not provided|Pontocerebellar hypoplasia, type 11
β˜…β˜…β˜†β˜†2024β†’ Residue 317
NM_001199198.3(TBC1D23):c.614_615del (p.Phe205fs)Pathogenic
Pontocerebellar hypoplasia, type 11
β˜…β˜…β˜†β˜†2024β†’ Residue 205
NM_001199198.3(TBC1D23):c.603dup (p.Gly202fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2026β†’ Residue 202
NM_001199198.3(TBC1D23):c.743_744del (p.Gln248fs)Pathogenic
Pontocerebellar hypoplasia, type 11
β˜…β˜†β˜†β˜†2024β†’ Residue 248
NM_001199198.3(TBC1D23):c.630del (p.Thr211fs)Likely pathogenic
Pontocerebellar hypoplasia, type 11
β˜…β˜†β˜†β˜†2022β†’ Residue 211
NM_001199198.3(TBC1D23):c.1687+2T>ALikely pathogenic
Pontocerebellar hypoplasia, type 11
β˜…β˜†β˜†β˜†2020
NM_001199198.3(TBC1D23):c.1092+2T>APathogenic
Pontocerebellar hypoplasia, type 11
β˜…β˜†β˜†β˜†2020
NM_001199198.3(TBC1D23):c.1687+1G>CPathogenic
Pontocerebellar hypoplasia, type 11
β˜…β˜†β˜†β˜†2018
NM_001199198.3(TBC1D23):c.1018del (p.Val340fs)Pathogenic
Pontocerebellar hypoplasia, type 11
β˜…β˜†β˜†β˜†β†’ Residue 340
NM_001199198.3(TBC1D23):c.1250del (p.Ala417fs)Likely pathogenic
HP:0000750; HP:0001263
β˜†β˜†β˜†β˜†2025β†’ Residue 417
NM_001199198.3(TBC1D23):c.1526delinsAA (p.Ile509fs)Pathogenic
Pontocerebellar hypoplasia, type 11|Pontoneocerebellar hypoplasia
β˜†β˜†β˜†β˜†2017β†’ Residue 509
NM_001199198.3(TBC1D23):c.1475_1476del (p.Val492fs)Pathogenic
Pontocerebellar hypoplasia, type 11|Pontoneocerebellar hypoplasia
β˜†β˜†β˜†β˜†2017β†’ Residue 492
NM_001199198.3(TBC1D23):c.1687+1G>APathogenic
Pontocerebellar hypoplasia, type 11
β˜†β˜†β˜†β˜†2017
NM_001199198.3(TBC1D23):c.1687+2T>GPathogenic
Pontocerebellar hypoplasia, type 11|Pontoneocerebellar hypoplasia
β˜†β˜†β˜†β˜†2017
View on ClinVar β†—
Related Genes
C17orf75Protein interaction97%FAM91A1Protein interaction82%GLRX3Protein interaction79%OSGEPProtein interaction79%API5Protein interaction72%GOLGA1Protein interaction71%
Tissue Expression6 tissues
Bone Marrow
100%
Heart
72%
Ovary
58%
Liver
54%
Lung
51%
Brain
51%
Gene Interaction Network
Click a node to explore
TBC1D23C17orf75FAM91A1GLRX3OSGEPAPI5GOLGA1
PROTEIN STRUCTURE
Preparing viewer…
PDB6JM5 Β· 1.60 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.88LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.62 [0.44–0.88]
RankingsWhere TBC1D23 stands among ~20K protein-coding genes
  • #9,947of 20,598
    Most Researched42
  • #2,534of 5,498
    Most Pathogenic Variants14
  • #7,851of 17,882
    Most Constrained (LOEUF)0.88
Genes detectedTBC1D23
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
FAM91A1-TBC1D23 complex structure reveals human genetic variations susceptible for PCH.
PMID: 37903274
Proc Natl Acad Sci U S A Β· 2023
1.00
2
Structural and functional studies of TBC1D23 C-terminal domain provide a link between endosomal trafficking and PCH.
PMID: 31624125
Proc Natl Acad Sci U S A Β· 2019
0.90
3
TBC1 domain family member 23 interacts with Ras-related protein Rab-11A to promote poor prognosis of non-small-cell lung cancer via Ξ²1-integrin.
PMID: 34363324
J Cell Mol Med Β· 2021
0.80
4
Pontocerebellar hypoplasia type 11: Does the genetic defect determine timing of cerebellar pathology?
PMID: 32360255
Eur J Med Genet Β· 2020
0.70
5
A CRISPR/Cas9 screen reveals proteins at the endosome-Golgi interface that modulate cellular anti-sense oligonucleotide activity.
PMID: 40588516
Nat Commun Β· 2025
0.60