RNF11

Chr 1

ring finger protein 11

Also known as: CGI-123, SID1669

NCBI Gene: 26994 ENSG00000123091 UniProt: Q9Y3C5 OMIM: 612598

RNF11 encodes a RING-H2 finger protein that functions as an essential component of a ubiquitin-editing complex that terminates inflammatory signaling pathways by promoting RIPK1 degradation and downregulating NF-kappa-B activation. The gene shows significant constraint against loss-of-function variants (LOEUF 0.69), but pathogenic variants and associated human disease phenotypes have not yet been established. RNF11 expression is induced by mutant RET proteins associated with multiple endocrine neoplasia, suggesting potential involvement in endocrine signaling pathways.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene contains a RING-H2 finger motif, which is known to be important for protein-protein interactions. The expression of this gene has been shown to be induced by mutant RET proteins (MEN2A/MEN2B). The germline mutations in RET gene are known to be responsible for the development of multiple endocrine neoplasia (MEN). [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

GOFmechanismLOEUF 0.69

Clinical Summary— RNF11

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.58) — some intolerance to loss-of-function variants.

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ClinVar Variants

16 VUS of 21 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.69LOEUF

pLI 0.579

Z-score 2.08

OE 0.15 (0.05–0.69)

Moderately constrained

Typical tolerance to LoF variation

Missense Constraint?

1.48Z-score

OE missense 0.55 (0.44–0.70)

48 obs / 86.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.15 (0.05–0.69)

0≤0.351.4

Missense OE?0.55 (0.44–0.70)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 1 / 6.9Missense obs/exp: 48 / 86.7Syn Z: 0.32

This gene — mechanism propensity

0.5772th %ile

GOF

0.6737th %ile

LOF

0.4332th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction 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.

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

ClinVar Variant Classifications

21 submitted variants in ClinVar

ClinVar

Classification Summary

VUS16

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	16	16
Likely Benign	0	0
Benign	0	0
Total	16	16

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

View in ClinVar →

8 pathogenic / likely-pathogenic (of 12) ClinVar copy-number / structural variants overlap RNF11 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →