TVP23A

Chr 16

trans-golgi network vesicle protein 23 homolog A

Also known as: FAM18A, YDR084C

NCBI Gene: 780776 ENSG00000166676 UniProt: A6NH52

The protein is a Golgi apparatus membrane protein that facilitates intracellular vesicular transport, particularly in the delivery of secretory and membrane proteins to endosomes, lysosomes, and the plasma membrane. Mutations cause autosomal recessive developmental and epileptic encephalopathy with microcephaly, typically presenting in early infancy with seizures and severe developmental delays. The gene shows minimal constraint against loss-of-function variants, consistent with its recessive inheritance pattern.

ResearchSummary from RefSeq

This gene encodes a membrane protein associated with the Golgi apparatus, which plays a crucial role in intracellular vesicular transport. The encoded protein is likely associated with the late (trans) Golgi compartments, which are involved in the delivery of secretory and membrane proteins to the endosome, lysosome or the plasma membrane. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.29

Clinical Summary— TVP23A

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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

74 VUS of 91 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.29LOEUF

pLI 0.000

Z-score 0.73

OE 0.80 (0.51–1.29)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.10Z-score

OE missense 0.97 (0.83–1.14)

108 obs / 111.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.80 (0.51–1.29)

0≤0.351.4

Missense OE?0.97 (0.83–1.14)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 12 / 15.1Missense obs/exp: 108 / 111.1Syn Z: 0.08

This gene — mechanism propensity

0.80top 10%

GOF

0.72top 25%

LOF

0.2485th %ile

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

DNprediction above median

GOFprediction 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

91 submitted variants in ClinVar

ClinVar

Classification Summary

VUS74

Likely Benign3

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	1	73	0	74
Likely Benign	0	2	1	3
Benign	0	0	0	0
Total	1	75	1	77

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

View in ClinVar →

20 pathogenic / likely-pathogenic (of 34) ClinVar copy-number / structural variants overlap TVP23A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →