UBE2L6

Chr 11

ubiquitin conjugating enzyme E2 L6

Also known as: RIG-B, UBCH8

NCBI Gene: 9246 ENSG00000156587 UniProt: O14933 OMIM: 603890

The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s) and ubiquitin-protein ligases (E3s). This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. This enzyme is highly similar in primary structure to the enzyme encoded by the UBE2L3 gene. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, May 2011]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.34

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.34LOEUF

pLI 0.008

Z-score 0.99

OE 0.59 (0.29–1.34)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.54Z-score

OE missense 0.84 (0.71–1.01)

82 obs / 97.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.59 (0.29–1.34)

0≤0.351.4

Missense OE?0.84 (0.71–1.01)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 4 / 6.8Missense obs/exp: 82 / 97.1Syn Z: 0.23

Background carrier burden — how many people carry a rare variant somewhere in UBE2L6?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 320

217 rare PASS variants

Rare truncating (LoF)

1 in 2,400

33 rare PASS variants

Rare synonymous (reference)

1 in 510

81 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for UBE2L6. 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 360	1 in 4,100
South Asian	~43k	1 in 250	1 in 720
Remaining (unassigned)	~30k	1 in 260	1 in 2,700
European (Finnish)	~27k	≈ 1 in 5,300	none seen
Admixed American	~22k	1 in 280	1 in 2,000
African / African American	~21k	1 in 340	1 in 680
East Asian	~20k	1 in 260	1 in 650
Ashkenazi Jewish	~13k	≈ 1 in 6,500	none seen
Middle Eastern	~2,884	1 in 360	≈ 1 in 940

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 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓