RNF111

Chr 15

ring finger protein 111

Also known as: ARK, hRNF111

NCBI Gene: 54778 ENSG00000157450 UniProt: Q6ZNA4 OMIM: 605840

The protein encoded by this gene is a nuclear RING-domain containing E3 ubiquitin ligase. This protein interacts with the transforming growth factor (TGF) -beta/NODAL signaling pathway by promoting the ubiquitination and proteosomal degradation of negative regulators, like SMAD proteins, and thereby enhances TGF-beta target-gene transcription. As a modulator of the nodal signaling cascade, this gene plays a critical role in the induction of mesoderm during embryonic development. Alternative splicing of this gene results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2012]

OMIM Research

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.21

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.21LOEUF

pLI 1.000

Z-score 5.51

OE 0.09 (0.04–0.21)

Highly constrained

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

Missense Constraint?

0.32Z-score

OE missense 0.96 (0.89–1.03)

520 obs / 541.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.09 (0.04–0.21)

0≤0.351.4

Missense OE?0.96 (0.89–1.03)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 4 / 43.0Missense obs/exp: 520 / 541.0Syn Z: -1.10

Background carrier burden — how many people carry a rare variant somewhere in RNF111?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 36

1,342 rare PASS variants

Rare truncating (LoF)

1 in 3,800

61 rare PASS variants

Rare synonymous (reference)

1 in 120

484 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RNF111. 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 49	1 in 6,800
South Asian	~43k	1 in 54	1 in 1,100
Remaining (unassigned)	~30k	1 in 45	≈ 1 in 6,600
European (Finnish)	~27k	1 in 170	1 in 3,800
Admixed American	~22k	1 in 49	1 in 810
African / African American	~21k	1 in 50	≈ 1 in 10,000
East Asian	~20k	1 in 49	≈ 1 in 19,000
Ashkenazi Jewish	~13k	1 in 250	≈ 1 in 3,300
Middle Eastern	~2,884	1 in 52	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): 11 of 13 coding exons well covered in gnomAD exomes; exons 12, 14 marginal. Genomes: all 13.? see exons ↓