RPL35A

Chr 3AD

ribosomal protein L35a

Also known as: DBA5, L35A, eL33

NCBI Gene: 6165 ENSG00000182899 UniProt: P18077 OMIM: 180468

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 OMIM Research

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.411 OMIM phenotype

Clinical Summary— RPL35A

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.90) — some intolerance to loss-of-function variants.

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ClinVar Variants

14 unique Pathogenic / Likely Pathogenic· 66 VUS of 150 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — RPL35A

Authoritative clinical overview · Recommended first read

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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

This gene — mechanism propensity

0.2599th %ile

GOF

0.13100th %ile

LOF

0.85top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · 50% of P/LP variants are LoF · LOEUF 0.41

Literature Evidence

LOFWe show that RPL35A haploinsufficiency is a cause of DBA and we report a novel case with 3q27.2-qter deletion and immunodeficiency.1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

References

1.PMID 28432740 ↗

ClinVar Variant Classifications

150 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8

Likely Pathogenic6

VUS66

Likely Benign54

Benign6

Conflicting4

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	5	1	2	0	8
Likely Pathogenic	2	2	2	0	6
VUS	2	48	14	2	66
Likely Benign	0	2	29	23	54
Benign	0	0	6	0	6
Conflicting	—				4
Total	9	53	53	25	144

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

42 pathogenic / likely-pathogenic (of 60) ClinVar copy-number / structural variants overlap RPL35A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →