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…

Primary Disease Associations & Inheritance

Congenital disorder of glycosylation, type IIhMIM #611182

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · COG8-congenital disorder of glycosylation · AR · ClinGen 2026

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.13

LOEUF

LOF

Mechanism· G2P

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

Background carrier burden — how many people carry a rare variant somewhere in COG8?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 53

929 rare PASS variants

Rare truncating (LoF)

1 in 430

129 rare PASS variants

Rare synonymous (reference)

1 in 71

461 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for COG8. 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 94	1 in 1,000
South Asian	~43k	1 in 47	1 in 970
Remaining (unassigned)	~30k	1 in 50	1 in 380
European (Finnish)	~27k	1 in 180	1 in 1,000
Admixed American	~22k	1 in 49	1 in 610
African / African American	~21k	1 in 57	1 in 580
East Asian	~20k	1 in 64	1 in 1,300
Ashkenazi Jewish	~13k	1 in 290	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 52	none seen

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): All 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓