UCN3

Chr 10

urocortin 3

Also known as: SCP, SPC, UCNIII

This gene encodes urocortin 3, a peptide hormone secreted by pancreatic beta and alpha cells that regulates insulin secretion in response to glucose levels and suppresses food intake. Mutations cause maturity-onset diabetes of the young type 14 (MODY14), an autosomal dominant form of early-onset diabetes typically presenting in adolescence or young adulthood. The gene shows tolerance to loss-of-function variants, suggesting that complete loss of function may not be the primary disease mechanism in affected patients.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
7
Pubs (1 yr)
25
P/LP submissions
0%
P/LP missense
1.73
LOEUF
DN
Mechanism· predicted
Clinical SummaryUCN3
Population Constraint (gnomAD)
Low constraint (pLI 0.04) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
25 unique Pathogenic / Likely Pathogenic· 44 VUS of 78 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.73LOEUF
pLI 0.044
Z-score 0.55
OE 0.66 (0.261.73)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.14Z-score
OE missense 1.04 (0.891.23)
103 obs / 99.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.66 (0.261.73)
00.351.4
Missense OE1.04 (0.891.23)
00.61.4
Synonymous OE1.02
01.21.6
LoF obs/exp: 2 / 3.0Missense obs/exp: 103 / 99.0Syn Z: -0.10
DN
0.76top 25%
GOF
0.5269th %ile
LOF
0.3355th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

78 submitted variants in ClinVar

Classification Summary

Pathogenic23
Likely Pathogenic2
VUS44
Likely Benign6
Benign2
23
Pathogenic
2
Likely Pathogenic
44
VUS
6
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
23
0
23
Likely Pathogenic
0
0
2
0
2
VUS
0
34
10
0
44
Likely Benign
0
3
1
2
6
Benign
0
0
1
1
2
Total03737377

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

View in ClinVar →

Protein Context — Lollipop Plot

UCN3 · 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 →
Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗