RNF13

Chr 3AD

ring finger protein 13

Also known as: DEE73, EIEE73, RZF

NCBI Gene: 11342 ENSG00000082996 UniProt: O43567 OMIM: 609247

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

GOFmechanismADLOEUF 0.901 OMIM phenotype

Clinical Summary— RNF13

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

7 unique Pathogenic / Likely Pathogenic· 145 VUS of 312 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.90LOEUF

pLI 0.000

Z-score 1.86

OE 0.50 (0.29–0.90)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.90Z-score

OE missense 0.82 (0.72–0.93)

158 obs / 193.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.50 (0.29–0.90)

0≤0.351.4

Missense OE?0.82 (0.72–0.93)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

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

This gene — mechanism propensity

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), Moldov1

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

References

1.PMID 30595371 ↗

ClinVar Variant Classifications

312 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

Likely Pathogenic4

VUS145

Likely Benign110

Benign21

Conflicting16

Pathogenic

Likely Pathogenic

145

VUS

110

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	2	0	0	3
Likely Pathogenic	4	0	0	0	4
VUS	15	122	8	0	145
Likely Benign	1	16	35	58	110
Benign	1	14	5	1	21
Conflicting	—				16
Total	22	154	48	59	299

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

View in ClinVar →

21 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap RNF13 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →