CTDNEP1

Chr 17

CTD nuclear envelope phosphatase 1

Also known as: DULLARD, HSA011916, NET56

NCBI Gene: 23399 ENSG00000175826 UniProt: O95476 OMIM: 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.

OMIM ResearchSummary from RefSeq, UniProt

Enables protein serine/threonine phosphatase activity. Involved in several processes, including positive regulation of triglyceride biosynthetic process; protein dephosphorylation; and protein localization to nucleus. Located in endoplasmic reticulum membrane; lipid droplet; and nuclear membrane. Part of Nem1-Spo7 phosphatase complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.26

Clinical Summary— CTDNEP1

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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

16 VUS of 35 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 OE?0.00 (0.00–0.26)

0≤0.351.4

Missense OE?0.40 (0.32–0.50)

0≤0.61.4

Synonymous OE?1.18

0≤1.21.6

LoF obs/exp: 0 / 11.3Missense obs/exp: 56 / 140.7Syn Z: -1.03

This gene — mechanism propensity

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

35 submitted variants in ClinVar

ClinVar

Classification Summary

VUS16

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	16	16
Likely Benign	0	0
Benign	0	0
Total	16	16

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

View in ClinVar →

30 pathogenic / likely-pathogenic (of 41) ClinVar copy-number / structural variants overlap CTDNEP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →