RPL35A

Chr 3

ribosomal protein L35a

Also known as: DBA5, L35A, eL33

NCBI Gene: 6165 ENSG00000182899 UniProt: P18077

Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L35AE family of ribosomal proteins. It is located in the cytoplasm. The rat protein has been shown to bind to both initiator and elongator tRNAs, and thus, it is located at the P site, or P and A sites, of the ribosome. Although this gene was originally mapped to chromosome 18, it has been established that it is located at 3q29-qter. Alternative splicing results in multiple transcript variants. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Oct 2015]

GeneReviews Research

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtDiamond-Blackfan anemia 5

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

0.41

LOEUF

LOF

Mechanism· predicted

📖

GeneReview available — RPL35A

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.41LOEUF

pLI 0.895

Z-score 2.51

OE 0.00 (0.00–0.41)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.37Z-score

OE missense 0.52 (0.39–0.69)

33 obs / 63.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.41)

0≤0.351.4

Missense OE?0.52 (0.39–0.69)

0≤0.61.4

Synonymous OE?1.51

0≤1.21.6

LoF obs/exp: 0 / 7.3Missense obs/exp: 33 / 63.8Syn Z: -1.86

Background carrier burden — how many people carry a rare variant somewhere in RPL35A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 990

94 rare PASS variants

Rare truncating (LoF)

1 in 240,000

3 rare PASS variants

Rare synonymous (reference)

1 in 1,200

62 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RPL35A. 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 1,700	≈ 1 in 190,000
South Asian	~43k	1 in 980	none seen
Remaining (unassigned)	~30k	1 in 640	none seen
European (Finnish)	~27k	≈ 1 in 5,300	none seen
Admixed American	~22k	1 in 680	none seen
African / African American	~21k	1 in 1,300	none seen
East Asian	~20k	1 in 240	none seen
Ashkenazi Jewish	~13k	≈ 1 in 6,500	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): 3 of 4 coding exons well covered in gnomAD exomes; exon 5 marginal. Genomes: all 4.? see exons ↓