TBC1D23

Chr 3AR

TBC1 domain family member 23

Also known as: NS4ATP1, PCH11

NCBI Gene: 55773 ENSG00000036054 UniProt: Q9NUY8 OMIM: 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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.601 OMIM phenotype

Clinical Summary— TBC1D23

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

15 unique Pathogenic / Likely Pathogenic· 98 VUS of 161 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 OE?0.39 (0.26–0.60)

0≤0.351.4

Missense OE?0.72 (0.65–0.80)

0≤0.61.4

Synonymous OE?0.91

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

This gene — mechanism propensity

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

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

161 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9

Likely Pathogenic6

VUS98

Likely Benign13

Benign18

Conflicting1

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	9	0	0	0	9
Likely Pathogenic	6	0	0	0	6
VUS	1	91	5	1	98
Likely Benign	0	3	3	7	13
Benign	0	1	13	4	18
Conflicting	—				1
Total	16	95	21	12	145

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

View in ClinVar →

9 pathogenic / likely-pathogenic (of 13) ClinVar copy-number / structural variants overlap TBC1D23 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →