COG2

Chr 1AR

component of oligomeric golgi complex 2

Also known as: CDG2Q, LDLC

NCBI Gene: 22796 ENSG00000135775 UniProt: Q14746 OMIM: 606974

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a subunit of the conserved oligomeric Golgi complex that is required for maintaining normal structure and activity of the Golgi complex. The encoded protein specifically interacts with the USO1 vesicle docking protein and may be necessary for normal Golgi ribbon formation and trafficking of Golgi enzymes. Mutations of this gene are associated with abnormal glycosylation within the Golgi apparatus. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Feb 2009]

OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 0.591 OMIM phenotype

Clinical Summary— COG2

🧬

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.

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.59LOEUF

pLI 0.000

Z-score 3.63

OE 0.39 (0.26–0.59)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.85Z-score

OE missense 0.88 (0.81–0.96)

351 obs / 399.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.39 (0.26–0.59)

0≤0.351.4

Missense OE?0.88 (0.81–0.96)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 16 / 41.1Missense obs/exp: 351 / 399.0Syn Z: -1.04

This gene — mechanism propensity

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.