RPL21

Chr 13AD

ribosomal protein L21

Also known as: HYPT12, L21, eL21

RPL21 encodes a ribosomal protein that is a component of the large 60S ribosomal subunit responsible for protein synthesis. Mutations cause hypotrichosis 12, an autosomal dominant condition characterized by sparse hair growth. The gene is highly constrained against loss-of-function variants (pLI 0.84, LOEUF 0.46), indicating that functional copies are critical for normal development.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.461 OMIM phenotype
Clinical SummaryRPL21
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.84) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
32 unique Pathogenic / Likely Pathogenic· 17 VUS of 69 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.46LOEUF
pLI 0.837
Z-score 2.69
OE 0.10 (0.030.46)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.53Z-score
OE missense 0.54 (0.430.69)
48 obs / 88.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.10 (0.030.46)
00.351.4
Missense OE0.54 (0.430.69)
00.61.4
Synonymous OE1.15
01.21.6
LoF obs/exp: 1 / 10.4Missense obs/exp: 48 / 88.4Syn Z: -0.62
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongRPL21-related hypotrichosisOTHERAD
DN
0.2399th %ile
GOF
0.2298th %ile
LOF
0.78top 5%

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

LOFprediction above median · LOEUF 0.46

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

69 submitted variants in ClinVar

Classification Summary

Pathogenic30
Likely Pathogenic2
VUS17
Likely Benign7
Benign13
30
Pathogenic
2
Likely Pathogenic
17
VUS
7
Likely Benign
13
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
29
0
30
Likely Pathogenic
0
0
2
0
2
VUS
0
11
5
1
17
Likely Benign
0
0
1
6
7
Benign
0
0
12
1
13
Total01249869

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

View in ClinVar →

Protein Context — Lollipop Plot

RPL21 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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