DET1

Chr 15

DET1 partner of COP1 E3 ubiquitin ligase

NCBI Gene: 55070 ENSG00000140543 UniProt: Q7L5Y6 OMIM: 608727

The protein is a component of the E3 ubiquitin ligase DCX DET1-COP1 complex that mediates ubiquitination and degradation of target proteins including JUN. Mutations cause autosomal recessive intellectual disability with seizures and hypotonia. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.43), suggesting intolerance to complete loss of function.

OMIM ResearchSummary from RefSeq, UniProt

Enables ubiquitin protein ligase binding activity and ubiquitin-like ligase-substrate adaptor activity. Involved in positive regulation of proteasomal ubiquitin-dependent protein catabolic process; protein ubiquitination; and protein-containing complex assembly. Part of Cul4A-RING E3 ubiquitin ligase complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.43

Clinical Summary— DET1

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.68) — some intolerance to loss-of-function variants.

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ClinVar Variants

91 VUS of 103 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.43LOEUF

pLI 0.679

Z-score 3.46

OE 0.19 (0.09–0.43)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.83Z-score

OE missense 0.87 (0.79–0.96)

297 obs / 339.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.19 (0.09–0.43)

0≤0.351.4

Missense OE?0.87 (0.79–0.96)

0≤0.61.4

Synonymous OE?1.26

0≤1.21.6

LoF obs/exp: 4 / 21.2Missense obs/exp: 297 / 339.8Syn Z: -2.25

This gene — mechanism propensity

0.4586th %ile

GOF

0.2895th %ile

LOF

0.65top 25%

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

LOFprediction above median · LOEUF 0.43

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

103 submitted variants in ClinVar

ClinVar

Classification Summary

VUS91

Likely Benign5

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	91	0	91
Likely Benign	0	5	5
Benign	0	0	0
Total	91	5	96

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

View in ClinVar →

33 pathogenic / likely-pathogenic (of 35) ClinVar copy-number / structural variants overlap DET1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →