CDRT15

Chr 17

CMT1A duplicated region transcript 15

The protein encoded by this gene functions as a component of the ribosome involved in protein synthesis. Mutations cause autosomal recessive neurodevelopmental disorder with severe intellectual disability, seizures, and brain malformations. This gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely incompatible with normal development.

MultiplemechanismLOEUF 1.89
Clinical SummaryCDRT15
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
112 unique Pathogenic / Likely Pathogenic· 37 VUS of 155 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.89LOEUF
pLI 0.000
Z-score -0.66
OE 1.29 (0.731.89)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.57Z-score
OE missense 1.16 (1.001.36)
111 obs / 95.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.29 (0.731.89)
00.351.4
Missense OE1.16 (1.001.36)
00.61.4
Synonymous OE1.05
01.21.6
LoF obs/exp: 8 / 6.2Missense obs/exp: 111 / 95.4Syn Z: -0.25
DN
0.6551th %ile
GOF
0.7029th %ile
LOF
0.3067th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

155 submitted variants in ClinVar

Classification Summary

Pathogenic108
Likely Pathogenic4
VUS37
Likely Benign1
108
Pathogenic
4
Likely Pathogenic
37
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
108
0
108
Likely Pathogenic
0
0
4
0
4
VUS
1
30
6
0
37
Likely Benign
0
0
1
0
1
Benign
0
0
0
0
0
Total1301190150

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

View in ClinVar →

Protein Context — Lollipop Plot

CDRT15 · 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
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found