COG8

Chr 16

component of oligomeric golgi complex 8

Also known as: CDG2H, DOR1

NCBI Gene: 84342 ENSG00000213380 UniProt: Q96MW5 OMIM: 606979

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).

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein that is a component of the conserved oligomeric Golgi (COG) complex, a multiprotein complex that plays a structural role in the Golgi apparatus, and is involved in intracellular membrane trafficking and glycoprotein modification. Mutations in this gene cause congenital disorder of glycosylation, type IIh, a disease that is characterized by under-glycosylated serum proteins, and whose symptoms include severe psychomotor retardation, failure to thrive, seizures, and dairy and wheat product intolerance. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 1.131 OMIM phenotype

Clinical Summary— COG8

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Gene-Disease Validity (ClinGen)

COG8-congenital disorder of glycosylation · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

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

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ClinVar Variants

17 unique Pathogenic / Likely Pathogenic· 205 VUS of 362 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.13LOEUF

pLI 0.000

Z-score 1.09

OE 0.75 (0.50–1.13)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.09Z-score

OE missense 1.01 (0.93–1.10)

375 obs / 369.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.75 (0.50–1.13)

0≤0.351.4

Missense OE?1.01 (0.93–1.10)

0≤0.61.4

Synonymous OE?1.14

0≤1.21.6

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

This gene — mechanism propensity

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

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

362 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5

Likely Pathogenic12

VUS205

Likely Benign91

Benign17

Conflicting23

Pathogenic

Likely Pathogenic

205

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	5	0	0	0	5
Likely Pathogenic	12	0	0	0	12
VUS	7	184	8	6	205
Likely Benign	0	13	21	57	91
Benign	0	2	13	2	17
Conflicting	—				23
Total	24	199	42	65	353

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

View in ClinVar →

23 pathogenic / likely-pathogenic (of 38) ClinVar copy-number / structural variants overlap COG8 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →