DCUN1D1

Chr 3

defective in cullin neddylation 1 domain containing 1

Also known as: DCNL1, DCUN1L1, RP42, SCCRO, SCRO, Tes3

NCBI Gene: 54165 ENSG00000043093 UniProt: Q96GG9 OMIM: 605905

Enables cullin family protein binding activity. Involved in positive regulation of protein neddylation and regulation of protein ubiquitination. Located in cytosol and nucleoplasm. Part of ubiquitin ligase complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.28

Clinical Summary— DCUN1D1

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

14 VUS of 25 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.28LOEUF

pLI 0.985

Z-score 3.62

OE 0.06 (0.02–0.28)

Highly constrained

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

Missense Constraint?

1.98Z-score

OE missense 0.51 (0.42–0.63)

67 obs / 130.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.06 (0.02–0.28)

0≤0.351.4

Missense OE?0.51 (0.42–0.63)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 1 / 17.2Missense obs/exp: 67 / 130.7Syn Z: 0.09

This gene — mechanism propensity

0.4388th %ile

GOF

0.73top 25%

LOF

0.51top 25%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFLOEUF 0.28

GOFprediction 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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

25 submitted variants in ClinVar

ClinVar

Classification Summary

VUS14

Benign1

VUS

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	14	0	14
Likely Benign	0	0	0
Benign	0	1	1
Total	14	1	15

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

View in ClinVar →

33 pathogenic / likely-pathogenic (of 36) ClinVar copy-number / structural variants overlap DCUN1D1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →