CTDSPL

Chr 3

CTD small phosphatase like

Also known as: C3orf8, HYA22, PSR1, RBSP3, SCP3

NCBI Gene: 10217ENSG00000144677UniProt: O15194OMIM: 608592

CTDSPL encodes a phosphatase that dephosphorylates the C-terminal domain of RNA polymerase II and is recruited by REST to silence neuronal genes in non-neuronal cells. The gene shows low constraint to loss-of-function variants (pLI = 0.003, LOEUF = 0.961), and no specific Mendelian diseases have been definitively associated with CTDSPL mutations to date. Further research is needed to establish clear genotype-phenotype correlations for this gene.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.96
Clinical Summary— CTDSPL
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
11 unique Pathogenic / Likely Pathogenic· 37 VUS of 54 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.96LOEUF
pLI 0.003
Z-score 1.67
OE 0.49 (0.27–0.96)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
2.08Z-score
OE missense 0.54 (0.46–0.65)
89 obs / 164.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.49 (0.27–0.96)
0≤0.351.4
Missense OE0.54 (0.46–0.65)
0≤0.61.4
Synonymous OE0.91
0≤1.21.6
LoF obs/exp: 6 / 12.3Missense obs/exp: 89 / 164.1Syn Z: 0.54
DN
0.6745th %ile
GOF
0.5267th %ile
LOF
0.2969th %ile

The highest-scoring mechanism for this gene is dominant-negative.

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

54 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic1
VUS37
10
Pathogenic
1
Likely Pathogenic
37
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
10
0
10
Likely Pathogenic
0
0
1
0
1
VUS
0
28
9
0
37
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total02820048

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

View in ClinVar →

Protein Context — Lollipop Plot

CTDSPL · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
miR-100-5p Enhances Cell Cycle-Mediated Chemoresistance by Modulating the CTDSPL/pRB/E2F1 Signaling Pathway in Oxaliplatin-Resistant Colorectal Cancer Cells.
Chen YP et al.·Oncol Res
2026Open Access
MicroRNA-18a prevents senescence of mesenchymal stem cells by targeting CTDSPL.
Sun B et al.·Aging (Albany NY)
2024Open Access
Hsa-miR-503-5p regulates CTDSPL to accelerate cisplatin resistance and angiogenesis of lung adenocarcinoma cells.
Han J et al.·Chem Biol Drug Des
2023
The miR-181 family promotes cell cycle by targeting CTDSPL, a phosphatase-like tumor suppressor in uveal melanoma.
Zhang L et al.·J Exp Clin Cancer Res
2018Open Access
Integration of ALV into CTDSPL and CTDSPL2 genes in B-cell lymphomas promotes cell immortalization, migration and survival.
Winans S et al.·Oncotarget
2017Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients