UNC13B

Chr 9

unc-13 homolog B

Also known as: MUNC13, UNC13, Unc13h2, munc13-2

NCBI Gene: 10497ENSG00000198722UniProt: O14795

This gene is expressed in the kidney cortical epithelial cells and is upregulated by hyperglycemia. The encoded protein shares a high level of similarity to the rat homolog, and contains 3 C2 domains and a diacylglycerol-binding C1 domain. Hyperglycemia increases the levels of diacylglycerol, which has been shown to induce apoptosis in cells transfected with this gene and thus contribute to the renal cell complications of hyperglycemia. Studies in other species also indicate a role for this protein in the priming step of synaptic vesicle exocytosis. [provided by RefSeq, Jul 2008]

334
ClinVar variants
71
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— UNC13B
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
71 Pathogenic / Likely Pathogenic· 218 VUS of 334 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.59LOEUF
pLI 0.000
Z-score 4.99
OE 0.46 (0.36–0.59)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.45Z-score
OE missense 0.87 (0.82–0.92)
794 obs / 917.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.46 (0.36–0.59)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.87 (0.82–0.92)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.91
0≤1.21.6
LoF obs/exp: 45 / 98.4Missense obs/exp: 794 / 917.3Syn Z: 1.30

ClinVar Variant Classifications

334 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic63
Likely Pathogenic8
VUS218
Likely Benign13
Benign5
63
Pathogenic
8
Likely Pathogenic
218
VUS
13
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
63
0
63
Likely Pathogenic
0
0
8
0
8
VUS
1
207
10
0
218
Likely Benign
0
9
1
3
13
Benign
0
2
1
2
5
Total1218835307

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

View in ClinVar →

Protein Context — Lollipop Plot

UNC13B · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
UNC13 HOMOLOG B; UNC13B
MIM #605836 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
UNC13B variants associated with partial epilepsy with favourable outcome.
Wang J et al.·Brain
2021
Rare UNC13B variations and risk of schizophrenia: Whole-exome sequencing in a multiplex family and follow-up resequencing and a case-control study.
Egawa J et al.·Am J Med Genet B Neuropsychiatr Genet
2016Case report
De novo UNC13B mutation identified in a bipolar disorder patient increases a rare exon-skipping variant.
Nakamura T et al.·Neuropsychopharmacol Rep
2018
Genetic associations in diabetic nephropathy: a meta-analysis.
Mooyaart AL et al.·Diabetologia
2011Meta-analysis
Development and clinical validation of a novel 9-gene prognostic model based on multi-omics in pancreatic adenocarcinoma.
Xu D et al.·Pharmacol Res
2021Functional
Going Deep into Synaptic Vesicle Machinery Genes and Migraine Susceptibility - A Case-Control Association Study.
Quintas M et al.·Headache
2020
Identification of diagnostic and prognostic phospholipid biomarkers in idiopathic pulmonary fibrosis via machine learning and in vivo validation.
Yang L et al.·Hum Genomics
2025
Linkage of Alzheimer disease families with Puerto Rican ancestry identifies a chromosome 9 locus.
Rajabli F et al.·Neurobiol Aging
2021
Identification of Prognostic Organic Cation and Anion Transporters in Different Cancer Entities by In Silico Analysis.
Edemir B·Int J Mol Sci
2020
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools