COG2

Chr 1AR

component of oligomeric golgi complex 2

This protein is a subunit of the conserved oligomeric Golgi complex required for maintaining normal Golgi structure and function, specifically interacting with vesicle docking proteins and enabling proper trafficking of Golgi enzymes. Mutations cause congenital disorder of glycosylation type IIq, inherited in an autosomal recessive pattern. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.591), and abnormal glycosylation within the Golgi apparatus underlies the disease pathophysiology.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismARLOEUF 0.591 OMIM phenotype
Clinical SummaryCOG2
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Gene-Disease Validity (ClinGen)
congenital disorder of glycosylation, type IIq · ARLimited

Limited evidence — not for standalone diagnostic reporting

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

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.59LOEUF
pLI 0.000
Z-score 3.63
OE 0.39 (0.260.59)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.85Z-score
OE missense 0.88 (0.810.96)
351 obs / 399.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.39 (0.260.59)
00.351.4
Missense OE0.88 (0.810.96)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 16 / 41.1Missense obs/exp: 351 / 399.0Syn Z: -1.04
DN
0.7033th %ile
GOF
0.5759th %ile
LOF
0.2776th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

COG2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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