TVP23C

Chr 17

trans-golgi network vesicle protein 23 homolog C

Also known as: FAM18B2

NCBI Gene: 201158 ENSG00000175106 UniProt: Q96ET8

The protein is predicted to function in protein secretion and vesicle-mediated transport at the Golgi membrane. Mutations in this gene have not been definitively associated with any recognized human disease or syndrome. The gene appears to tolerate loss-of-function variants well based on population genetic data.

ResearchSummary from RefSeq

Predicted to be involved in protein secretion and vesicle-mediated transport. Predicted to be located in membrane. Predicted to be active in Golgi membrane. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.43

Clinical Summary— TVP23C

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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

1 VUS of 2 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.43LOEUF

pLI 0.000

Z-score 0.60

OE 0.80 (0.47–1.43)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.52Z-score

OE missense 1.12 (0.99–1.27)

167 obs / 149.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.80 (0.47–1.43)

0≤0.351.4

Missense OE?1.12 (0.99–1.27)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 8 / 10.1Missense obs/exp: 167 / 149.0Syn Z: 0.01

This gene — mechanism propensity

0.6258th %ile

GOF

0.7030th %ile

LOF

0.3550th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

2 submitted variants in ClinVar

ClinVar

Classification Summary

VUS1

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	1	0	1
Likely Benign	0	1	1
Benign	0	0	0
Total	1	1	2

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

View in ClinVar →

120 pathogenic / likely-pathogenic (of 127) ClinVar copy-number / structural variants overlap TVP23C — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →