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…

Primary Disease Associations & Inheritance

?Congenital disorder of glycosylation, type IIqMIM #617395

Clinical highlights

Gene–disease validity (ClinGen)

Limited · congenital disorder of glycosylation, type IIq · AR · ClinGen 2024

not for standalone diagnostic reporting

Active trials

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Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.59

LOEUF

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in COG2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 82

889 rare PASS variants

Rare truncating (LoF)

1 in 2,200

119 rare PASS variants

Rare synonymous (reference)

1 in 91

352 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for COG2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 92	1 in 2,800
South Asian	~43k	1 in 61	1 in 2,200
Remaining (unassigned)	~30k	1 in 66	1 in 800
European (Finnish)	~27k	1 in 350	1 in 790
Admixed American	~22k	1 in 79	1 in 1,800
African / African American	~21k	1 in 51	1 in 1,100
East Asian	~20k	1 in 95	1 in 1,600
Ashkenazi Jewish	~13k	1 in 260	1 in 2,100
Middle Eastern	~2,884	1 in 66	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 13 of 18 coding exons well covered in gnomAD exomes; exons 3, 5, 6, 11, 14 marginal. Genomes: all 18.? see exons ↓