COG6

Chr 13AR

component of oligomeric golgi complex 6

Also known as: CDG2L, COD2, SHNS

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

This gene encodes a subunit of the conserved oligomeric Golgi complex that is required for maintaining normal structure and activity of the Golgi apparatus. The encoded protein is organized with conserved oligomeric Golgi complex components 5, 7 and 8 into a sub-complex referred to as lobe B. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Feb 2009]

OMIM ResearchGenerating clinical summary…

ARLOEUF 1.022 OMIM phenotypes

Clinical Summary— COG6

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Gene-Disease Validity (ClinGen)

COG6-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

36 unique Pathogenic / Likely Pathogenic· 196 VUS of 452 total submissions

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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

ClinVar Variant Classifications

452 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16

Likely Pathogenic20

VUS196

Likely Benign103

Benign81

Conflicting14

Pathogenic

Likely Pathogenic

196

VUS

103

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	14	1	1	0	16
Likely Pathogenic	16	1	2	1	20
VUS	5	150	34	7	196
Likely Benign	0	5	53	45	103
Benign	0	4	76	1	81
Conflicting	—				14
Total	35	161	166	54	430

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

View in ClinVar →

48 pathogenic / likely-pathogenic (of 53) ClinVar copy-number / structural variants overlap COG6 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →