SUMO1

small ubiquitin like modifier 1

Basic information

Region (hg38): 2:202206181-202238599

Previous symbols: [ "UBL1" ]

Links

ENSG00000116030 ∙ NCBI:7341 ∙ OMIM:601912 ∙ HGNC:12502 ∙ Uniprot:P63165 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• orofacial cleft 5 (Limited), mode of inheritance: AD
• orofacial cleft 10 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Orofacial cleft 10	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial	16990542

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SUMO1 gene.

• Orofacial cleft 10 (14 variants)
• not provided (3 variants)
• Cleft Lip +/- Cleft Palate, Autosomal Dominant (1 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SUMO1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			1			1
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding			12	2	3	17
Total	0	0	13	2	3

Variants in SUMO1

This is a list of pathogenic ClinVar variants found in the SUMO1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-202206215-G-A		Orofacial cleft 10	Uncertain significance (Jan 12, 2018)
2-202206309-C-G		Orofacial cleft 10	Uncertain significance (Jan 12, 2018)
2-202206369-T-C		Orofacial cleft 10	Uncertain significance (Jan 13, 2018)
2-202206439-C-T		Orofacial cleft 10	Uncertain significance (Jan 13, 2018)
2-202206477-T-A		Orofacial cleft 10	Uncertain significance (Apr 27, 2017)
2-202206500-G-C		Orofacial cleft 10	Uncertain significance (Jan 13, 2018)
2-202206529-T-C		Orofacial cleft 10	Uncertain significance (Jan 12, 2018)
2-202206708-C-A		Orofacial cleft 10	Uncertain significance (Jan 13, 2018)
2-202206778-T-C		Orofacial cleft 10	Uncertain significance (Jan 13, 2018)
2-202207275-G-A		not specified	Uncertain significance (Mar 14, 2023)
2-202214442-G-A		Orofacial cleft 10	Uncertain significance (Jan 12, 2018)
2-202214444-TAAAAAAG-T		Cleft Lip +/- Cleft Palate, Autosomal Dominant	Uncertain significance (Jun 14, 2016)
2-202214584-T-C			Benign (Nov 12, 2018)
2-202220266-G-C			Benign (May 22, 2021)
2-202238189-A-G			Benign (Jun 19, 2021)
2-202238483-A-C		Orofacial cleft 10	Likely benign (Jan 13, 2018)
2-202238499-G-A		Orofacial cleft 10	Uncertain significance (Apr 27, 2017)
2-202238534-T-C		Orofacial cleft 10	Uncertain significance (Jan 12, 2018)
2-202238545-C-T		Orofacial cleft 10	Likely benign (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SUMO1	protein_coding	protein_coding	ENST00000392246	5	32429

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.861	0.137	124729	0	1	124730	0.00000401

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.51	18	47.1	0.382	0.00000199	666
Missense in Polyphen		2	10.599	0.1887		153
Synonymous	-0.185	16	15.1	1.06	7.31e-7	164
Loss of Function	2.36	0	6.47	0.00	2.71e-7	91

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000883	0.00000883
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Ubiquitin-like protein that can be covalently attached to proteins as a monomer or a lysine-linked polymer. Covalent attachment via an isopeptide bond to its substrates requires prior activation by the E1 complex SAE1-SAE2 and linkage to the E2 enzyme UBE2I, and can be promoted by E3 ligases such as PIAS1-4, RANBP2 or CBX4. This post-translational modification on lysine residues of proteins plays a crucial role in a number of cellular processes such as nuclear transport, DNA replication and repair, mitosis and signal transduction. Involved for instance in targeting RANGAP1 to the nuclear pore complex protein RANBP2. Covalently attached to the voltage-gated potassium channel KCNB1; this modulates the gating characteristics of KCNB1 (PubMed:19223394). Polymeric SUMO1 chains are also susceptible to polyubiquitination which functions as a signal for proteasomal degradation of modified proteins. May also regulate a network of genes involved in palate development. Covalently attached to ZFHX3 (PubMed:24651376). {ECO:0000269|PubMed:18408734, ECO:0000269|PubMed:18538659, ECO:0000269|PubMed:19223394, ECO:0000269|PubMed:21965678, ECO:0000269|PubMed:24651376, ECO:0000269|PubMed:9019411, ECO:0000269|PubMed:9162015}.
• Disease: DISEASE: Non-syndromic orofacial cleft 10 (OFC10) [MIM:613705]: A birth defect consisting of cleft lips with or without cleft palate. Cleft lips are associated with cleft palate in two-third of cases. A cleft lip can occur on one or both sides and range in severity from a simple notch in the upper lip to a complete opening in the lip extending into the floor of the nostril and involving the upper gum. {ECO:0000269|PubMed:16990542}. Note=The disease is caused by mutations affecting the gene represented in this entry. A chromosomal aberration involving SUMO1 is the cause of OFC10. Translocation t(2;8)(q33.1;q24.3). The breakpoint occurred in the SUMO1 gene and resulted in haploinsufficiency confirmed by protein assays.
• Pathway: RNA transport - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);TGF-Ncore;Androgen receptor signaling pathway;TP53 Network;TGF-beta Signaling Pathway;Exercise-induced Circadian Regulation;HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA);DNA Repair;Gene expression (Transcription);Nonhomologous End-Joining (NHEJ);DNA Double-Strand Break Repair;sumoylation by ranbp2 regulates transcriptional repression;role of parkin in ubiquitin-proteasomal pathway;Generic Transcription Pathway;Cytokine Signaling in Immune system;SUMO is conjugated to E1 (UBA2:SAE1);SUMO is transferred from E1 to E2 (UBE2I, UBC9);SUMO is proteolytically processed;SUMOylation of DNA damage response and repair proteins;SUMOylation of transcription factors;SUMOylation of transcription cofactors;Homology Directed Repair;SUMOylation of chromatin organization proteins;SUMOylation of RNA binding proteins;Post-translational protein modification;SUMOylation of DNA replication proteins;SUMO E3 ligases SUMOylate target proteins;basic mechanisms of sumoylation;Metabolism of proteins;RNA Polymerase II Transcription;Regulation of IFNG signaling;G2/M DNA damage checkpoint;G2/M Checkpoints;Cell Cycle Checkpoints;Immune System;Processing and activation of SUMO;sumoylation as a mechanism to modulate ctbp-dependent gene responses;SUMOylation;regulation of transcriptional activity by pml;TGF_beta_Receptor;Signaling events mediated by HDAC Class II;Interferon gamma signaling;Negative regulation of activity of TFAP2 (AP-2) family transcription factors;Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors;Cell Cycle;TNFalpha;Formation of Incision Complex in GG-NER;Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks;DNA Double Strand Break Response;Global Genome Nucleotide Excision Repair (GG-NER);Interferon Signaling;Processing of DNA double-strand break ends;Sumoylation by RanBP2 regulates transcriptional repression;Signaling events mediated by HDAC Class I;Nucleotide Excision Repair (Consensus)

Recessive Scores

• pRec: 0.697

Intolerance Scores

• rvis_EVS: 0.1
• rvis_percentile_EVS: 60.96

Haploinsufficiency Scores

• hipred: Y
• hipred_score: 0.830
• ghis: 0.673

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.998

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Low	Low	Low
Primary Immunodeficiency	Low	Low	Low
Cancer	Low	Low	Low

Mouse Genome Informatics

• Gene name: Sumo1
• Phenotype: digestive/alimentary phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; growth/size/body region phenotype; craniofacial phenotype; cellular phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;DNA repair;double-strand break repair via nonhomologous end joining;viral process;protein sumoylation;PML body organization;positive regulation of protein complex assembly;positive regulation of proteasomal ubiquitin-dependent protein catabolic process;regulation of protein localization;cellular response to heat;negative regulation of DNA binding;negative regulation of DNA-binding transcription factor activity;negative regulation of action potential;negative regulation of transcription, DNA-templated;protein stabilization;roof of mouth development;regulation of interferon-gamma-mediated signaling pathway;cellular response to cadmium ion;regulation of cardiac muscle cell contraction;protein localization to nuclear pore;positive regulation of calcium-transporting ATPase activity;negative regulation of delayed rectifier potassium channel activity
• Cellular component: heterochromatin;fibrillar center;XY body;nucleus;nuclear envelope;nuclear pore;nucleoplasm;nucleolus;cytosol;plasma membrane;voltage-gated potassium channel complex;nuclear body;PML body;nuclear speck;dendrite;SUMO activating enzyme complex;nuclear membrane;synapse;nuclear stress granule
• Molecular function: transcription corepressor binding;RNA binding;protein binding;protein C-terminus binding;transcription factor binding;potassium channel regulator activity;SUMO transferase activity;enzyme binding;protein binding, bridging;protein tag;ubiquitin protein ligase binding;glucocorticoid receptor binding;small protein activating enzyme binding;ubiquitin-like protein ligase binding