DCUN1D5

Chr 11

defective in cullin neddylation 1 domain containing 5

Also known as: DCNL5, SCCRO5

NCBI Gene: 84259 ENSG00000137692 UniProt: Q9BTE7 OMIM: 616522

Enables cullin family protein binding activity. Involved in DNA damage response; positive regulation of protein neddylation; and regulation of cell growth. Located in nucleus and spindle. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.19

LOEUF· LoF intol.

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.19LOEUF

pLI 0.994

Z-score 3.63

OE 0.00 (0.00–0.19)

Highly constrained

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

Missense Constraint?

2.28Z-score

OE missense 0.42 (0.33–0.53)

51 obs / 121.6 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.19)

0≤0.351.4

Missense OE?0.42 (0.33–0.53)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 0 / 15.4Missense obs/exp: 51 / 121.6Syn Z: 0.41

Background carrier burden — how many people carry a rare variant somewhere in DCUN1D5?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 220

189 rare PASS variants

Rare truncating (LoF)

1 in 20,000

18 rare PASS variants

Rare synonymous (reference)

1 in 1,100

93 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DCUN1D5. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 260	1 in 14,000
South Asian	~43k	1 in 240	≈ 1 in 41,000
Remaining (unassigned)	~30k	1 in 270	none seen
European (Finnish)	~27k	1 in 780	≈ 1 in 13,000
Admixed American	~22k	1 in 220	none seen
African / African American	~21k	1 in 390	none seen
East Asian	~20k	1 in 510	≈ 1 in 19,000
Ashkenazi Jewish	~13k	1 in 400	none seen
Middle Eastern	~2,884	1 in 410	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 6 of 8 coding exons well covered in gnomAD exomes; exons 3, 5 marginal. Genomes: all 8.? see exons ↓