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CIR1

Chr 20

ubiquitin conjugating enzyme E2 V1

Also known as: CIR1, CROC-1, CROC1, UBE2V, UEV-1, UEV1, UEV1A

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 encoded by this gene is located in the nucleus and can cause transcriptional activation of the human FOS proto-oncogene. It is thought to be involved in the control of differentiation by altering cell cycle behavior. Alternatively spliced transcript variants encoding multiple isoforms have been described for this gene, and multiple pseudogenes of this gene have been identified. Co-transcription of this gene and the neighboring upstream gene generates a rare transcript (Kua-UEV), which encodes a fusion protein comprised of sequence sharing identity with each individual gene product. [provided by RefSeq, Apr 2012]

OMIMResearchGenerating clinical summary…
MultiplemechanismLOEUF 0.99
Clinical SummaryCIR1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
10 VUS of 10 total submissions
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.99LOEUF
pLI 0.000
Z-score 1.60
OE 0.64 (0.430.99)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
1.04Z-score
OE missense 0.80 (0.710.91)
179 obs / 222.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.64 (0.430.99)
00.351.4
Missense OE?0.80 (0.710.91)
00.61.4
Synonymous OE?1.13
01.21.6
LoF obs/exp: 15 / 23.3Missense obs/exp: 179 / 222.6Syn Z: -0.91

This gene — mechanism propensity

DN
0.77top 25%
GOF
0.6834th %ile
LOF
0.3551th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

10 submitted variants in ClinVar

Classification Summary

VUS10
10
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
0
10
0
0
10
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total0100010

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

View in ClinVar →

5 pathogenic / likely-pathogenic (of 9) ClinVar copy-number / structural variants overlap CIR1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

CIR1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →