RNF152

Chr 18

ring finger protein 152

NCBI Gene: 220441 ENSG00000176641 UniProt: Q8N8N0 OMIM: 616512

RNF152 encodes an E3 ubiquitin ligase that negatively regulates mTORC1 signaling by ubiquitinating RagA and RHEB proteins in response to amino acid availability. Pathogenic variants cause autosomal recessive intellectual disability with developmental delay, hypotonia, and feeding difficulties in infancy. The gene shows moderate tolerance to loss-of-function variants in the general population.

OMIM ResearchSummary from RefSeq, UniProt

Enables small GTPase binding activity and ubiquitin protein ligase activity. Involved in several processes, including cellular response to amino acid starvation; negative regulation of TORC1 signaling; and protein ubiquitination. Located in lysosomal membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.13

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.13LOEUF

pLI 0.129

Z-score 1.39

OE 0.36 (0.15–1.13)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.65Z-score

OE missense 0.84 (0.72–0.98)

116 obs / 137.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.36 (0.15–1.13)

0≤0.351.4

Missense OE?0.84 (0.72–0.98)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 2 / 5.5Missense obs/exp: 116 / 137.4Syn Z: 0.72

Background carrier burden — how many people carry a rare variant somewhere in RNF152?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 290

280 rare PASS variants

Rare truncating (LoF)

1 in 6,600

31 rare PASS variants

Rare synonymous (reference)

1 in 230

121 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RNF152. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 340	1 in 8,100
South Asian	~43k	1 in 140	≈ 1 in 14,000
Remaining (unassigned)	~30k	1 in 290	none seen
European (Finnish)	~27k	1 in 3,000	≈ 1 in 6,700
Admixed American	~22k	1 in 300	1 in 2,000
African / African American	~21k	1 in 150	1 in 3,600
East Asian	~20k	1 in 150	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 730	none seen
Middle Eastern	~2,884	1 in 150	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓