ERGIC2

Chr 12

ERGIC and golgi 2

Also known as: CDA14, Erv41, PTX1, cd002

ERGIC2 encodes a protein involved in transport between the endoplasmic reticulum and Golgi apparatus. Mutations cause autosomal recessive spastic paraplegia with intellectual disability and thin corpus callosum. The gene shows moderate constraint against loss-of-function variants, suggesting some intolerance to complete protein loss.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
0
Pubs (1 yr)
33
P/LP submissions
0%
P/LP missense
0.63
LOEUF
DN
Mechanism· predicted
Clinical SummaryERGIC2
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.
📋
ClinVar Variants
33 unique Pathogenic / Likely Pathogenic· 49 VUS of 103 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.63LOEUF
pLI 0.013
Z-score 2.82
OE 0.33 (0.190.63)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.07Z-score
OE missense 0.78 (0.690.90)
152 obs / 193.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.33 (0.190.63)
00.351.4
Missense OE0.78 (0.690.90)
00.61.4
Synonymous OE0.89
01.21.6
LoF obs/exp: 7 / 20.9Missense obs/exp: 152 / 193.7Syn Z: 0.69
DN
0.6550th %ile
GOF
0.5170th %ile
LOF
0.3068th %ile

The highest-scoring mechanism for this gene is dominant-negative.

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

103 submitted variants in ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic2
VUS49
Likely Benign2
Benign1
31
Pathogenic
2
Likely Pathogenic
49
VUS
2
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
31
0
31
Likely Pathogenic
0
0
2
0
2
VUS
0
40
9
0
49
Likely Benign
0
2
0
0
2
Benign
0
0
1
0
1
Total04243085

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

View in ClinVar →

Protein Context — Lollipop Plot

ERGIC2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC