PEDS1-UBE2V1

Chr 20

PEDS1-UBE2V1 readthrough

Also known as: CROC-1B, CROC1B, KUA-UEV, TMEM189-UBE2V1

NCBI Gene: 387522 ENSG00000124208 OMIM: 610994

The protein encoded by this read-through transcript contains UEV1 B domains and localizes to the cytoplasm, but its biological function remains undetermined. This gene shows low constraint against loss-of-function variants (pLI = 0.008, LOEUF = 0.67), and no established disease associations have been reported in the literature.

OMIM ResearchSummary from RefSeq

The TMEM189-UEV mRNA is an infrequent but naturally occurring read-through transcript of the neighboring TMEM189 and UBE2V1 genes. Ubiquitin-conjugating E2 enzyme variant proteins constitute a distinct subfamily within the E2 protein family. They have sequence similarity to other ubiquitin-conjugating enzymes but lack the conserved cysteine residue that is critical for the catalytic activity of E2s. The protein produced by this transcript has UEV1 B domains but the protein is localized to the cytoplasm rather than to the nucleus. The significance of this read-through mRNA and the function of its protein product has not yet been determined. [provided by RefSeq, Oct 2010]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.67

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.67LOEUF

pLI 0.008

Z-score 2.65

OE 0.36 (0.20–0.67)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

2.43Z-score

OE missense 0.53 (0.45–0.62)

112 obs / 211.4 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.36 (0.20–0.67)

0≤0.351.4

Missense OE?0.53 (0.45–0.62)

0≤0.61.4

Synonymous OE?1.17

0≤1.21.6

LoF obs/exp: 7 / 19.7Missense obs/exp: 112 / 211.4Syn Z: -1.18

Background carrier burden — how many people carry a rare variant somewhere in PEDS1-UBE2V1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 260

353 rare PASS variants

Rare truncating (LoF)

1 in 13,000

35 rare PASS variants

Rare synonymous (reference)

1 in 140

197 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PEDS1-UBE2V1. 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 190	1 in 20,000
South Asian	~43k	1 in 180	1 in 7,500
Remaining (unassigned)	~30k	1 in 310	≈ 1 in 14,000
European (Finnish)	~27k	1 in 590	1 in 3,600
Admixed American	~22k	1 in 200	≈ 1 in 11,000
African / African American	~21k	1 in 160	≈ 1 in 21,000
East Asian	~20k	1 in 380	≈ 1 in 9,900
Ashkenazi Jewish	~13k	1 in 920	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 220	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): 7 of 8 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 8.? see exons ↓