RNF13

Chr 3AD

ring finger protein 13

Also known as: DEE73, EIEE73, RZF

NCBI Gene: 11342ENSG00000082996UniProt: O43567

The protein encoded by this gene contains a RING zinc finger, a motif known to be involved in protein-protein interactions. The specific function of this gene has not yet been determined. Alternatively spliced transcript variants that encode the same protein have been reported. A pseudogene, which is also located on chromosome 3, has been defined for this gene. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 73MIM #618379
AD
319
ClinVar variants
28
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— RNF13
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
28 Pathogenic / Likely Pathogenic· 145 VUS of 319 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.90LOEUF
pLI 0.000
Z-score 1.86
OE 0.50 (0.29–0.90)
Tolerant

Typical tolerance to LoF variation

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.
0.90Z-score
OE missense 0.82 (0.72–0.93)
158 obs / 193.2 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.0.50 (0.29–0.90)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.82 (0.72–0.93)
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.1.09
0≤1.21.6
LoF obs/exp: 8 / 16.0Missense obs/exp: 158 / 193.2Syn Z: -0.62

ClinVar Variant Classifications

319 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic6
VUS145
Likely Benign110
Benign21
Conflicting15
22
Pathogenic
6
Likely Pathogenic
145
VUS
110
Likely Benign
21
Benign
15
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
20
0
22
Likely Pathogenic
1
0
5
0
6
VUS
12
119
14
0
145
Likely Benign
0
16
35
59
110
Benign
1
14
5
1
21
Conflicting
—15
Total141517960319

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

View 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.

Gene2Phenotype Curations

RNF13-related congenital microcephaly, epileptic encephalopathy, blindness, and failure to thrive

strong
ADGain Of FunctionAltered Gene Product Structure
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Developmental and epileptic encephalopathy 73

MIM #618379

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
RNF13 protects neurons against ischemia-reperfusion injury via stabilizing p62-mediated Nrf2/HO-1 signaling pathway.
Wang Q et al.·Cell Commun Signal
2024
A novel de novo RNF13 variant in developmental and epileptic encephalopathy 73: genotype-phenotype correlation and literature review.
Zhang Q et al.·BMC Neurol
2026Review
Heterozygous gain of function variants in a critical region of RNF13 cause congenital microcephaly, epileptic encephalopathy, blindness, and failure to thrive.
Taylor A et al.·Am J Med Genet A
2023Review
AP-1 contributes to endosomal targeting of the ubiquitin ligase RNF13 via a secondary and novel non-canonical binding motif.
Cabana VC et al.·J Cell Sci
2024
Recurrent PAK2 rearrangements in poroma with folliculo-sebaceous differentiation.
Kervarrec T et al.·Histopathology
2023
[Genetic analysis of a pedigree affected with Intellectual disability due to variants of two different genes].
Shi T et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2024Case report
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