RC3H2

Chr 9

ring finger and CCCH-type domains 2

Also known as: MNAB, RNF164

RC3H2 encodes a post-transcriptional repressor that binds to conserved decay elements in mRNAs to promote their degradation, regulates microRNA processing, and functions as a ubiquitin E3 ligase involved in protein polyubiquitination. Mutations cause autosomal dominant neurodevelopmental disorder through loss-of-function mechanisms. The protein is highly intolerant to loss-of-function variants, indicating haploinsufficiency as the likely pathogenic mechanism.

OMIMResearchSummary from RefSeq, UniProt, Mechanism
LOFmechanismLOEUF 0.17
Clinical SummaryRC3H2
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.17LOEUF
pLI 1.000
Z-score 6.72
OE 0.08 (0.040.17)
Highly constrained

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

Missense Constraint
2.45Z-score
OE missense 0.73 (0.670.79)
463 obs / 636.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.08 (0.040.17)
00.351.4
Missense OE0.73 (0.670.79)
00.61.4
Synonymous OE0.95
01.21.6
LoF obs/exp: 5 / 62.2Missense obs/exp: 463 / 636.9Syn Z: 0.65
DN
0.2499th %ile
GOF
0.3987th %ile
LOF
0.80top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.17

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

RC3H2 · 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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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC