RCE1

Chr 11

Ras converting CAAX endopeptidase 1

Also known as: FACE2, RCE1A, RCE1B

NCBI Gene: 9986 ENSG00000173653 UniProt: Q9Y256 OMIM: 605385

This metalloproteinase processes prenylated proteins by removing the C-terminal three amino acids from CAAX motif-containing proteins including Ras proteins, which is essential for proper cellular signaling. Mutations cause autosomal recessive intellectual disability with dysmorphic features and developmental delay. The gene shows moderate constraint against loss-of-function variants.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes an integral membrane protein which is classified as a member of the metalloproteinase family. This enzyme is thought to function in the maintenance and processing of CAAX-type prenylated proteins. [provided by RefSeq, Jul 2008]

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

0.62

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.62LOEUF

pLI 0.160

Z-score 2.59

OE 0.27 (0.13–0.62)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.78Z-score

OE missense 0.84 (0.74–0.96)

158 obs / 188.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.27 (0.13–0.62)

0≤0.351.4

Missense OE?0.84 (0.74–0.96)

0≤0.61.4

Synonymous OE?1.34

0≤1.21.6

LoF obs/exp: 4 / 14.8Missense obs/exp: 158 / 188.2Syn Z: -2.43

Background carrier burden — how many people carry a rare variant somewhere in RCE1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 220

456 rare PASS variants

Rare truncating (LoF)

1 in 3,200

74 rare PASS variants

Rare synonymous (reference)

1 in 140

280 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RCE1. 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 190	1 in 4,100
South Asian	~43k	1 in 170	1 in 5,200
Remaining (unassigned)	~30k	1 in 240	none seen
European (Finnish)	~27k	1 in 560	1 in 1,900
Admixed American	~22k	1 in 130	1 in 2,600
African / African American	~21k	1 in 280	1 in 1,800
East Asian	~20k	1 in 210	1 in 1,600
Ashkenazi Jewish	~13k	1 in 450	≈ 1 in 5,800
Middle Eastern	~2,884	1 in 130	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 8 coding exons well covered in gnomAD exomes and genomes.? see exons ↓