TBC1D23

Chr 3AR

TBC1 domain family member 23

Also known as: NS4ATP1, PCH11

NCBI Gene: 55773ENSG00000036054UniProt: Q9NUY8OMIM: 617687

TBC1D23 encodes a Rab GTPase-activating protein that facilitates endosome-to-Golgi trafficking by bridging the WASH complex on endosome-derived vesicles to golgins at the trans-Golgi, and plays a role in cortical neuron positioning during brain development. Mutations cause pontocerebellar hypoplasia type 11, a severe neurodevelopmental disorder with autosomal recessive inheritance. The gene is highly constrained against loss-of-function variants (pLI near 0, LOEUF 0.601), indicating that complete protein loss is likely incompatible with normal development.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.601 OMIM phenotype
Clinical Summary— TBC1D23
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
24 unique Pathogenic / Likely Pathogenic· 102 VUS of 174 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.60LOEUF
pLI 0.000
Z-score 3.50
OE 0.39 (0.26–0.60)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.89Z-score
OE missense 0.72 (0.65–0.80)
258 obs / 358.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.39 (0.26–0.60)
0≤0.351.4
Missense OE0.72 (0.65–0.80)
0≤0.61.4
Synonymous OE0.91
0≤1.21.6
LoF obs/exp: 15 / 38.5Missense obs/exp: 258 / 358.7Syn Z: 0.79
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveTBC1D23-related non-degenerative pontocerebellar hypoplasiaLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6258th %ile
GOF
0.5563th %ile
LOF
0.3066th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

174 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic8
VUS102
Likely Benign13
Benign18
Conflicting1
16
Pathogenic
8
Likely Pathogenic
102
VUS
13
Likely Benign
18
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
0
7
0
16
Likely Pathogenic
6
0
2
0
8
VUS
1
91
9
1
102
Likely Benign
0
3
3
7
13
Benign
0
1
13
4
18
Conflicting
—1
Total16953412158

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TBC1D23 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Homozygous Mutations in TBC1D23 Lead to a Non-degenerative Form of Pontocerebellar Hypoplasia.
Marin-Valencia I et al.·Am J Hum Genet
2017
TBC1D23 drives lymphatic metastasis in pancreatic ductal adenocarcinoma by altering EGFR cell surface dynamics and signaling.
Chao YJ et al.·Cell Oncol (Dordr)
2026
Mapping autosomal recessive intellectual disability: combined microarray and exome sequencing identifies 26 novel candidate genes in 192 consanguineous families.
Harripaul R et al.·Mol Psychiatry
2018
Identification and functional analysis of a novel TBC1D23 pathogenic variant in a Chinese family with pontocerebellar hypoplasia.
Liu K et al.·Hum Genomics
2025Functional
Clinical, radiological, and genetic variation in pontocerebellar hypoplasia disorder and our clinical experience.
Bilge S et al.·Ital J Pediatr
2022
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients