SUMO1

Chr 2Isolated cases

small ubiquitin like modifier 1

Also known as: DAP1, GMP1, OFC10, PIC1, SMT3, SMT3C, SMT3H3, UBL1

NCBI Gene: 7341 ENSG00000116030 UniProt: P63165 OMIM: 601912

The protein functions as a small ubiquitin-like modifier that covalently attaches to target proteins to regulate nuclear transport, DNA replication and repair, transcriptional regulation, and signal transduction rather than targeting proteins for degradation. Pathogenic variants cause an autosomal recessive neurodevelopmental disorder characterized by intellectual disability, developmental delay, and cleft palate. The gene is highly constrained against loss-of-function variants in the population, indicating that such variants are likely to be pathogenic when present.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a protein that is a member of the SUMO (small ubiquitin-like modifier) protein family. It functions in a manner similar to ubiquitin in that it is bound to target proteins as part of a post-translational modification system. However, unlike ubiquitin which targets proteins for degradation, this protein is involved in a variety of cellular processes, such as nuclear transport, transcriptional regulation, apoptosis, and protein stability. It is not active until the last four amino acids of the carboxy-terminus have been cleaved off. Several pseudogenes have been reported for this gene. Alternate transcriptional splice variants encoding different isoforms have been characterized. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismIsolated casesLOEUF 0.461 OMIM phenotype

Clinical Summary— SUMO1

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.86) — some intolerance to loss-of-function variants.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 14 VUS of 31 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.46LOEUF

pLI 0.861

Z-score 2.36

OE 0.00 (0.00–0.46)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.51Z-score

OE missense 0.38 (0.26–0.57)

18 obs / 47.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.46)

0≤0.351.4

Missense OE?0.38 (0.26–0.57)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 0 / 6.5Missense obs/exp: 18 / 47.1Syn Z: -0.19

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

limitedSUMO1-related cleft lip with or without cleft palateLOFAD

This gene — mechanism propensity

0.3892th %ile

GOF

0.2895th %ile

LOF

0.75top 10%

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

LOFprediction above median · LOEUF 0.46

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

31 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1

VUS14

Likely Benign2

Benign4

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	0	0	0
Likely Pathogenic	0	1	1
VUS	2	12	14
Likely Benign	0	2	2
Benign	0	4	4
Total	2	19	21

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

View in ClinVar →

29 pathogenic / likely-pathogenic (of 33) ClinVar copy-number / structural variants overlap SUMO1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →