RPL17

Chr 18AD

ribosomal protein L17

Also known as: DBA22, L17, PD-1, RPL23, uL22

RPL17 encodes a ribosomal protein that is a component of the large 60S ribosomal subunit responsible for protein synthesis. Mutations cause Diamond-Blackfan anemia 22, inherited in an autosomal dominant pattern. The gene is highly constrained against loss-of-function variants (pLI 0.92, LOEUF 0.38), reflecting the essential nature of ribosomal function.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Diamond-Blackfan anemia 22MIM #621262
AD
0
Active trials
11
Pubs (1 yr)
42
P/LP submissions
0%
P/LP missense
0.38
LOEUF
LOF
Mechanism· predicted
Clinical SummaryRPL17
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.92). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
40 unique Pathogenic / Likely Pathogenic· 15 VUS of 58 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.38LOEUF
pLI 0.924
Z-score 3.03
OE 0.08 (0.030.38)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.34Z-score
OE missense 0.65 (0.540.79)
74 obs / 114.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.08 (0.030.38)
00.351.4
Missense OE0.65 (0.540.79)
00.61.4
Synonymous OE1.12
01.21.6
LoF obs/exp: 1 / 12.6Missense obs/exp: 74 / 114.2Syn Z: -0.58
DN
0.4388th %ile
GOF
0.1899th %ile
LOF
0.71top 10%

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

LOFprediction above median · LOEUF 0.38

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

ClinVar Variant Classifications

58 submitted variants in ClinVar

Classification Summary

Pathogenic37
Likely Pathogenic3
VUS15
Likely Benign1
Benign1
37
Pathogenic
3
Likely Pathogenic
15
VUS
1
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
37
0
37
Likely Pathogenic
1
0
2
0
3
VUS
0
12
3
0
15
Likely Benign
0
0
1
0
1
Benign
0
0
1
0
1
Total11244057

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

View in ClinVar →

Protein Context — Lollipop Plot

RPL17 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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