UNC13A

Chr 19

unc-13 homolog A

Also known as: IDDSF, Munc13-1, NEDHES, NEDSMS

NCBI Gene: 23025ENSG00000130477UniProt: Q9UPW8

This gene encodes a member of the UNC13 family. UNC13 proteins bind to phorbol esters and diacylglycerol and play important roles in neurotransmitter release at synapses. Single nucleotide polymorphisms in this gene may be associated with sporadic amyotrophic lateral sclerosis. [provided by RefSeq, Feb 2012]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtNeurodevelopmental disorder with hypotonia, epilepsy, and absent speech
UniProtNeurodevelopmental disorder with speech delay, movement abnormalities, and seizures
UniProtIntellectual development disorder with seizures and dysmorphic facies

Clinical highlights

Gene-disease validity (ClinGen)
neurodevelopmental disorder with speech delay, movement abnormalities, and seizures · ADDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total
Interpreting a novel variant
Curated mechanisms (Gene2Phenotype) include both loss of function and gain of function. Which applies is variant-dependent — do not assume a null variant is, or isn’t, the pathogenic class without checking the specific variant.Curated gene-level mechanism — a prior for triage, not a per-variant call.
0
Active trials
37
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.16
LOEUF· LoF intol.
Multiple*
Mechanism· G2P
📖
GeneReview available — UNC13A
Authoritative clinical overview · Recommended first read
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?
0.16LOEUF
pLI 1.000
Z-score 8.39
OE 0.09 (0.05–0.16)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
5.63Z-score
OE missense 0.50 (0.47–0.54)
513 obs / 1018.3 exp
Constrained

Extremely missense-constrained (top ~0.01%)

Observed / Expected Ratios?
LoF OE?0.09 (0.05–0.16)
0≤0.351.4
Missense OE?0.50 (0.47–0.54)
0≤0.61.4
Synonymous OE?1.00
0≤1.21.6
LoF obs/exp: 9 / 99.1Missense obs/exp: 513 / 1018.3Syn Z: -0.03

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

UNC13A · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients