ESYT3

Chr 3

extended synaptotagmin 3

Also known as: CHR3SYT, E-Syt3, FAM62C

NCBI Gene: 83850 ENSG00000158220 UniProt: A0FGR9 OMIM: 616692

Predicted to enable calcium ion binding activity and phospholipid binding activity. Predicted to be involved in endoplasmic reticulum-plasma membrane tethering and lipid transport. Located in cytoplasmic side of plasma membrane; endoplasmic reticulum membrane; and endoplasmic reticulum-plasma membrane contact site. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

GOFmechanismLOEUF 1.11

Clinical Summary— ESYT3

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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

123 VUS of 148 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?

1.11LOEUF

pLI 0.000

Z-score 0.93

OE 0.86 (0.67–1.11)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.07Z-score

OE missense 0.99 (0.92–1.07)

490 obs / 494.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.86 (0.67–1.11)

0≤0.351.4

Missense OE?0.99 (0.92–1.07)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 42 / 49.0Missense obs/exp: 490 / 494.4Syn Z: 0.92

This gene — mechanism propensity

0.5771th %ile

GOF

0.6542th %ile

LOF

0.49top 25%

The highest-scoring mechanism for this gene is gain-of-function.

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

148 submitted variants in ClinVar

ClinVar

Classification Summary

VUS123

Likely Benign6

123

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	123	123
Likely Benign	6	6
Benign	0	0
Total	129	129

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

View in ClinVar →

22 pathogenic / likely-pathogenic (of 34) ClinVar copy-number / structural variants overlap ESYT3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →