COG8

Chr 16

component of oligomeric golgi complex 8

Also known as: CDG2H, DOR1

The protein is a component of the conserved oligomeric Golgi (COG) complex that maintains Golgi structure and enables intracellular membrane trafficking and glycoprotein modification. Mutations cause congenital disorder of glycosylation type IIh, characterized by severe psychomotor retardation, failure to thrive, seizures, and intolerance to dairy and wheat products due to under-glycosylated serum proteins. This follows autosomal recessive inheritance and the gene shows tolerance to loss-of-function variants (pLI near zero).

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismLOEUF 1.131 OMIM phenotype
Clinical SummaryCOG8
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Gene-Disease Validity (ClinGen)
COG8-congenital disorder of glycosylation · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📖
GeneReview available — COG8
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.13LOEUF
pLI 0.000
Z-score 1.09
OE 0.75 (0.501.13)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.09Z-score
OE missense 1.01 (0.931.10)
375 obs / 369.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.75 (0.501.13)
00.351.4
Missense OE1.01 (0.931.10)
00.61.4
Synonymous OE1.14
01.21.6
LoF obs/exp: 16 / 21.4Missense obs/exp: 375 / 369.9Syn Z: -1.35
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveCOG8-related congenital disorder of glycosylationLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6163th %ile
GOF
0.6444th %ile
LOF
0.3648th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

COG8 · 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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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC