SENP8

Chr 15

SUMO peptidase family member, NEDD8 specific

Also known as: DEN1, NEDP1, PRSC2

NCBI Gene: 123228 ENSG00000166192 UniProt: Q96LD8 OMIM: 608659

This gene encodes a cysteine protease that is a member of the sentrin-specific protease family. The encoded protein is involved in processing and deconjugation of the ubiquitin-like protein termed, neural precursor cell expressed developmentally downregulated 8. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Oct 2009]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.74

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.74LOEUF

pLI 0.001

Z-score 0.19

OE 0.91 (0.47–1.74)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.28Z-score

OE missense 0.65 (0.54–0.80)

70 obs / 107.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.91 (0.47–1.74)

0≤0.351.4

Missense OE?0.65 (0.54–0.80)

0≤0.61.4

Synonymous OE?1.20

0≤1.21.6

LoF obs/exp: 5 / 5.5Missense obs/exp: 70 / 107.4Syn Z: -1.03

Background carrier burden — how many people carry a rare variant somewhere in SENP8?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 340

218 rare PASS variants

Rare truncating (LoF)

1 in 8,100

31 rare PASS variants

Rare synonymous (reference)

1 in 370

104 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SENP8. 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 320	1 in 8,200
South Asian	~43k	1 in 340	≈ 1 in 14,000
Remaining (unassigned)	~30k	1 in 260	1 in 4,300
European (Finnish)	~27k	1 in 2,400	none seen
Admixed American	~22k	1 in 530	≈ 1 in 22,000
African / African American	~21k	1 in 370	≈ 1 in 17,000
East Asian	~20k	1 in 810	1 in 2,600
Ashkenazi Jewish	~13k	1 in 2,200	1 in 930
Middle Eastern	~2,884	1 in 360	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): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓