RNF2

Chr 1AD

ring finger protein 2

Also known as: BAP-1, BAP1, DING, HIPI3, LUSYAM, RING1B, RING2

NCBI Gene: 6045 ENSG00000121481 UniProt: Q99496 OMIM: 608985

Polycomb group (PcG) of proteins form the multiprotein complexes that are important for the transcription repression of various genes involved in development and cell proliferation. The protein encoded by this gene is one of the PcG proteins. It has been shown to interact with, and suppress the activity of, transcription factor CP2 (TFCP2/CP2). Studies of the mouse counterpart suggested the involvement of this gene in the specification of anterior-posterior axis, as well as in cell proliferation in early development. This protein was also found to interact with huntingtin interacting protein 2 (HIP2), an ubiquitin-conjugating enzyme, and possess ubiquitin ligase activity. [provided by RefSeq, Jul 2008]

OMIM Research

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Luo-Schoch-Yamamoto syndromeMIM #619460

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Luo-Schoch-Yamamoto syndrome; no ClinGen or GenCC tier

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

0.17

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.17LOEUF

pLI 0.997

Z-score 3.88

OE 0.00 (0.00–0.17)

Highly constrained

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

Missense Constraint?

2.52Z-score

OE missense 0.48 (0.40–0.57)

87 obs / 183.2 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.17)

0≤0.351.4

Missense OE?0.48 (0.40–0.57)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 0 / 17.5Missense obs/exp: 87 / 183.2Syn Z: 0.40

Background carrier burden — how many people carry a rare variant somewhere in RNF2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 600

271 rare PASS variants

Rare truncating (LoF)

1 in 32,000

12 rare PASS variants

Rare synonymous (reference)

1 in 540

146 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RNF2. 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 910	1 in 56,000
South Asian	~43k	1 in 350	≈ 1 in 43,000
Remaining (unassigned)	~30k	1 in 400	≈ 1 in 30,000
European (Finnish)	~27k	1 in 3,800	≈ 1 in 27,000
Admixed American	~22k	1 in 430	none seen
African / African American	~21k	1 in 470	≈ 1 in 21,000
East Asian	~20k	1 in 270	none seen
Ashkenazi Jewish	~13k	1 in 2,200	none seen
Middle Eastern	~2,884	≈ 1 in 720	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 6 coding exons well covered in gnomAD exomes and genomes.? see exons ↓