RPS27A

Chr 2

ribosomal protein S27a

Also known as: CEP80, HEL112, S27A, UBA80, UBCEP1, UBCEP80, eS31

NCBI Gene: 6233 ENSG00000143947 UniProt: P62979 OMIM: 191343

Ubiquitin, a highly conserved protein that has a major role in targeting cellular proteins for degradation by the 26S proteosome, is synthesized as a precursor protein consisting of either polyubiquitin chains or a single ubiquitin fused to an unrelated protein. This gene encodes a fusion protein consisting of ubiquitin at the N terminus and ribosomal protein S27a at the C terminus. When expressed in yeast, the protein is post-translationally processed, generating free ubiquitin monomer and ribosomal protein S27a. Ribosomal protein S27a is a component of the 40S subunit of the ribosome and belongs to the S27AE family of ribosomal proteins. It contains C4-type zinc finger domains and is located in the cytoplasm. Pseudogenes derived from this gene are present in the genome. As with ribosomal protein S27a, ribosomal protein L40 is also synthesized as a fusion protein with ubiquitin; similarly, ribosomal protein S30 is synthesized as a fusion protein with the ubiquitin-like protein fubi. Multiple alternatively spliced transcript variants that encode the same proteins have been identified.[provided by RefSeq, Sep 2008]

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

0.37

LOEUF

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.37LOEUF

pLI 0.919

Z-score 2.63

OE 0.00 (0.00–0.37)

Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.86Z-score

OE missense 0.74 (0.60–0.91)

62 obs / 84.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.37)

0≤0.351.4

Missense OE?0.74 (0.60–0.91)

0≤0.61.4

Synonymous OE?1.29

0≤1.21.6

LoF obs/exp: 0 / 8.1Missense obs/exp: 62 / 84.3Syn Z: -1.24

Background carrier burden — how many people carry a rare variant somewhere in RPS27A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 1,100

138 rare PASS variants

Rare truncating (LoF)

1 in 50,000

5 rare PASS variants

Rare synonymous (reference)

1 in 760

81 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RPS27A. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 8 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 1,100	≈ 1 in 140,000
South Asian	~43k	1 in 830	≈ 1 in 43,000
Remaining (unassigned)	~30k	1 in 540	none seen
Admixed American	~22k	1 in 510	none seen
African / African American	~21k	1 in 600	≈ 1 in 21,000
East Asian	~20k	1 in 840	none seen
Ashkenazi Jewish	~13k	1 in 870	none seen
Middle Eastern	~2,883	1 in 580	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 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓