COG6

Chr 13AR

component of oligomeric golgi complex 6

NCBI Gene: 57511 ENSG00000133103 UniProt: Q9Y2V7 OMIM: 606977

This gene encodes a subunit of the conserved oligomeric Golgi complex that maintains normal Golgi apparatus structure and function, specifically as part of the lobe B sub-complex with COG components 5, 7, and 8. Mutations cause congenital disorder of glycosylation type IIl and Shaheen syndrome, both inherited in an autosomal recessive pattern. The gene shows no significant constraint against loss-of-function variants (pLI near zero, LOEUF ~1), which is consistent with the recessive inheritance pattern where heterozygous carriers are typically unaffected.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Required for normal Golgi function

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Congenital disorder of glycosylation, type IIlMIM #614576

Shaheen syndromeMIM #615328

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · COG6-congenital disorder of glycosylation · AR · ClinGen 2024

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.02

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.02LOEUF

pLI 0.000

Z-score 1.46

OE 0.75 (0.56–1.02)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.18Z-score

OE missense 1.03 (0.94–1.12)

371 obs / 361.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.75 (0.56–1.02)

0≤0.351.4

Missense OE?1.03 (0.94–1.12)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 29 / 38.8Missense obs/exp: 371 / 361.2Syn Z: 0.54

Background carrier burden — how many people carry a rare variant somewhere in COG6?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 65

883 rare PASS variants

Rare truncating (LoF)

1 in 1,000

178 rare PASS variants

Rare synonymous (reference)

1 in 180

314 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for COG6. 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 91	1 in 1,100
South Asian	~43k	1 in 63	1 in 450
Remaining (unassigned)	~30k	1 in 55	1 in 1,300
European (Finnish)	~27k	1 in 350	1 in 1,600
Admixed American	~22k	1 in 61	1 in 750
African / African American	~21k	1 in 64	1 in 890
East Asian	~20k	1 in 70	1 in 1,200
Ashkenazi Jewish	~13k	1 in 260	1 in 1,900
Middle Eastern	~2,884	1 in 71	1 in 570

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.