CTDNEP1

Chr 17

CTD nuclear envelope phosphatase 1

Also known as: DULLARD, HSA011916, NET56

NCBI Gene: 23399ENSG00000175826UniProt: O95476OMIM: 610684

The protein is a serine/threonine phosphatase that forms an active complex with CNEP1R1 to dephosphorylate LPIN1 and LPIN2, which are key enzymes in fatty acid metabolism and conversion of phosphatidic acid to diacylglycerol. Mutations cause congenital lipodystrophy, a disorder affecting fat tissue distribution and metabolism, inherited in an autosomal recessive pattern. This gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely incompatible with normal development.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.26
Clinical Summary— CTDNEP1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
29 unique Pathogenic / Likely Pathogenic· 26 VUS of 74 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.26LOEUF
pLI 0.975
Z-score 3.12
OE 0.00 (0.00–0.26)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.54Z-score
OE missense 0.40 (0.32–0.50)
56 obs / 140.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.00 (0.00–0.26)
0≤0.351.4
Missense OE0.40 (0.32–0.50)
0≤0.61.4
Synonymous OE1.18
0≤1.21.6
LoF obs/exp: 0 / 11.3Missense obs/exp: 56 / 140.7Syn Z: -1.03
DN
0.3296th %ile
GOF
0.3887th %ile
LOF
0.66top 25%

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

LOFprediction above median · LOEUF 0.26

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

74 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic26
Likely Pathogenic3
VUS26
26
Pathogenic
3
Likely Pathogenic
26
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
26
0
26
Likely Pathogenic
0
0
3
0
3
VUS
0
16
10
0
26
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total01639055

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

View in ClinVar →

Protein Context — Lollipop Plot

CTDNEP1 · 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
Low CTDNEP1 Expression Predicts Poor Prognosis and Is Associated With Immune Modulation in Pancreatic Cancer.
Nii M et al.·Cancer Genomics Proteomics
2026Open Access
Structure and mechanism of the human CTDNEP1-NEP1R1 membrane protein phosphatase complex necessary to maintain ER membrane morphology.
Gao S et al.·Proc Natl Acad Sci U S A
2024Open AccessFunctional
Ctdnep1 phosphatase is required for negative regulation of RANKL-induced osteoclast differentiation in RAW264.7 cells.
Konno T et al.·Biochem Biophys Res Commun
2024
Loss of phosphatase CTDNEP1 potentiates aggressive medulloblastoma by triggering MYC amplification and genomic instability.
Luo Z et al.·Nat Commun
2023Open Access
Torsin and NEP1R1-CTDNEP1 phosphatase affect interphase nuclear pore complex insertion by lipid-dependent and lipid-independent mechanisms.
Jacquemyn J et al.·EMBO J
2021Open AccessFunctional
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