RNF13

Chr 3AD

ring finger protein 13

Also known as: DEE73, EIEE73, RZF

RNF13 encodes an E3 ubiquitin-protein ligase that regulates cell proliferation, apoptosis, and protein trafficking. Mutations cause developmental and epileptic encephalopathy 73, which follows an autosomal dominant inheritance pattern. This represents an early-onset neurodevelopmental disorder affecting both cognitive development and seizure control.

OMIMResearchSummary from RefSeq, OMIM, UniProt
GOFmechanismADLOEUF 0.901 OMIM phenotype
Clinical SummaryRNF13
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.90LOEUF
pLI 0.000
Z-score 1.86
OE 0.50 (0.290.90)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.90Z-score
OE missense 0.82 (0.720.93)
158 obs / 193.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.50 (0.290.90)
00.351.4
Missense OE0.82 (0.720.93)
00.61.4
Synonymous OE1.09
01.21.6
LoF obs/exp: 8 / 16.0Missense obs/exp: 158 / 193.2Syn Z: -0.62
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongRNF13-related congenital microcephaly, epileptic encephalopathy, blindness, and failure to thriveGOFAD
DN
0.6550th %ile
GOF
0.6932th %ile
LOF
0.2969th %ile

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

GOFprediction above median · 1 literature citation
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.

Literature Evidence

GOFHeterozygous RNF13 Gain-of-Function Variants Are Associated with Congenital Microcephaly, Epileptic Encephalopathy, Blindness, and Failure to Thrive.Edvardson S(1), Nicolae CM(2), Noh GJ(3), Burton JE(4), Punzi G(5), Shaag A(6), Bischetsrieder J(3), De Grassi A(5), Pierri CL(5), Elpeleg O(7), MoldovPMID:30595371

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

RNF13 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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