SENP3

Chr 17

SUMO specific peptidase 3

Also known as: SMT3IP1, SSP3, Ulp1

NCBI Gene: 26168 ENSG00000161956 UniProt: Q9H4L4 OMIM: 612844

SENP3 encodes a SUMO-specific protease that removes SUMO2 and SUMO3 modifications from target proteins, regulating processes including ribosomal RNA processing, transcriptional activation, and DNA repair. The gene is highly constrained against loss-of-function variants (pLI = 0.85, LOEUF = 0.36), but specific disease associations and inheritance patterns have not yet been established in the provided data.

OMIM ResearchSummary from RefSeq, UniProt

The reversible posttranslational modification of proteins by the addition of small ubiquitin-like SUMO proteins (see SUMO1; MIM 601912) is required for numerous biologic processes. SUMO-specific proteases, such as SENP3, are responsible for the initial processing of SUMO precursors to generate a C-terminal diglycine motif required for the conjugation reaction. They also have isopeptidase activity for the removal of SUMO from high molecular mass SUMO conjugates (Di Bacco et al., 2006 [PubMed 16738315]).[supplied by OMIM, Jun 2009]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.36

Clinical Summary— SENP3

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.85) — some intolerance to loss-of-function variants.

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ClinVar Variants

53 VUS of 54 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.36LOEUF

pLI 0.848

Z-score 4.32

OE 0.18 (0.10–0.36)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.56Z-score

OE missense 0.61 (0.54–0.68)

204 obs / 336.2 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.18 (0.10–0.36)

0≤0.351.4

Missense OE?0.61 (0.54–0.68)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 6 / 32.6Missense obs/exp: 204 / 336.2Syn Z: 0.30

This gene — mechanism propensity

0.3296th %ile

GOF

0.4480th %ile

LOF

0.68top 25%

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

LOFprediction above median · LOEUF 0.36

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

54 submitted variants in ClinVar

ClinVar

Classification Summary

VUS53

Likely Benign1

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	53	0	53
Likely Benign	0	1	1
Benign	0	0	0
Total	53	1	54

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

View in ClinVar →

21 pathogenic / likely-pathogenic (of 31) ClinVar copy-number / structural variants overlap SENP3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →