RNF166

Chr 16

ring finger protein 166

NCBI Gene: 115992 ENSG00000158717 UniProt: Q96A37 OMIM: 617178

The protein is an E3 ubiquitin ligase that promotes ubiquitination of substrates involved in interferon production and autophagy, including roles in antiviral responses and targeting bacteria for degradation. Mutations cause autosomal recessive early-onset epileptic encephalopathy with developmental delay, affecting the nervous system primarily in infancy and early childhood. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.614), consistent with recessive inheritance patterns.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in protein polyubiquitination and ubiquitin-dependent protein catabolic process. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 0.61

Clinical Summary— RNF166

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.20) despite low pLI — interpret in context.

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ClinVar Variants

51 VUS of 56 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.61LOEUF

pLI 0.487

Z-score 2.39

OE 0.20 (0.08–0.61)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.73Z-score

OE missense 0.81 (0.68–0.96)

91 obs / 112.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.20 (0.08–0.61)

0≤0.351.4

Missense OE?0.81 (0.68–0.96)

0≤0.61.4

Synonymous OE?1.30

0≤1.21.6

LoF obs/exp: 2 / 10.2Missense obs/exp: 91 / 112.9Syn Z: -1.68

ClinVar Variant Classifications

56 submitted variants in ClinVar

ClinVar

Classification Summary

VUS51

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	51	0	51
Likely Benign	0	1	1
Benign	0	0	0
Total	51	1	52

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

View in ClinVar →

66 pathogenic / likely-pathogenic (of 92) ClinVar copy-number / structural variants overlap RNF166 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →