SUMO4

Summary

SUMO4 (small ubiquitin like modifier 4, HGNC:21181) is a protein-coding gene on chromosome 6q25.1, encoding Small ubiquitin-related modifier 4 (Q6EEV6). Ubiquitin-like protein which can be covalently attached to target lysines as a monomer.

This gene is a member of the SUMO gene family. This family of genes encode small ubiquitin-related modifiers that are attached to proteins and control the target proteins’ subcellular localization, stability, or activity. The protein described in this record is located in the cytoplasm and specifically modifies IKBA, leading to negative regulation of NF-kappa-B-dependent transcription of the IL12B gene. A specific polymorphism in this SUMO gene, which leads to the M55V substitution, has been associated with type I diabetes. The RefSeq contains this polymorphism.

Source: NCBI Gene 387082 — RefSeq curated summary.

At a glance

• Gene–disease (curated): type 1 diabetes mellitus 5 (Limited, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 22 total — 1 pathogenic
• MANE Select transcript: NM_001002255

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21181
Approved symbol	SUMO4
Name	small ubiquitin like modifier 4
Location	6q25.1
Locus type	gene with protein product
Status	Approved
Aliases	dJ281H8.4
Ensembl gene	ENSG00000177688
Ensembl biotype	protein_coding
OMIM	608829
Entrez	387082

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000326669

RefSeq mRNA: 1 — MANE Select: NM_001002255 NM_001002255

CCDS: CCDS34549

Canonical transcript exons

ENST00000326669 — 1 exons

Exon	Start	End
ENSE00001269172	149400262	149401278

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 94.64.

FANTOM5 (CAGE): breadth broad, TPM avg 0.5718 / max 16.4304, expressed in 309 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
204243	0.5718	309

Top tissues by expression

294 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	94.64	gold quality
buccal mucosa cell	CL:0002336	94.59	silver quality
mammary duct	UBERON:0001765	93.91	gold quality
pylorus	UBERON:0001166	92.67	gold quality
renal medulla	UBERON:0000362	92.50	gold quality
cranial nerve II	UBERON:0000941	92.31	gold quality
cardia of stomach	UBERON:0001162	92.22	gold quality
epithelium of mammary gland	UBERON:0003244	91.88	gold quality
pharyngeal mucosa	UBERON:0000355	91.58	gold quality
superior surface of tongue	UBERON:0007371	91.31	gold quality
vena cava	UBERON:0004087	90.88	gold quality
epithelium of nasopharynx	UBERON:0001951	90.48	gold quality
urethra	UBERON:0000057	90.45	gold quality
periodontal ligament	UBERON:0008266	90.39	silver quality
cartilage tissue	UBERON:0002418	90.37	gold quality
cauda epididymis	UBERON:0004360	90.23	gold quality
ventral tegmental area	UBERON:0002691	90.20	gold quality
trigeminal ganglion	UBERON:0001675	89.95	gold quality
caput epididymis	UBERON:0004358	89.91	gold quality
saphenous vein	UBERON:0007318	89.86	gold quality
skin of hip	UBERON:0001554	89.78	gold quality
body of tongue	UBERON:0011876	89.75	silver quality
nipple	UBERON:0002030	89.74	gold quality
pericardium	UBERON:0002407	89.72	silver quality
subthalamic nucleus	UBERON:0001906	89.70	gold quality
pancreatic ductal cell	CL:0002079	89.61	gold quality
superficial temporal artery	UBERON:0001614	89.57	gold quality
sperm	CL:0000019	89.56	gold quality
tongue	UBERON:0001723	89.43	gold quality
inferior vagus X ganglion	UBERON:0005363	89.36	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.34

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFKB

miRNA regulators (miRDB)

34 targeting SUMO4, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-6516-3P	99.65	68.57	1238
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-4687-3P	99.48	66.41	968
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-20B-3P	99.29	67.05	784
HSA-MIR-625-5P	99.02	68.64	2031
HSA-MIR-1183	98.75	67.10	1116
HSA-MIR-16-1-3P	98.70	69.23	1538
HSA-MIR-1261	98.62	68.10	896
HSA-MIR-4252	98.45	66.37	987
HSA-MIR-6516-5P	98.42	70.19	1551
HSA-MIR-10526-3P	97.86	64.97	1342
HSA-MIR-3190-3P	97.61	66.95	1406

Literature-anchored findings (GeneRIF, showing 40)

• we report evidence for an association between T1D and multiple single-nucleotide polymorphisms in 197 kb of genomic DNA in the IDDM5 interval. (PMID:15247916)
• SUMO4 sumoylation may play an important role in the regulation of intracellular stress (PMID:16236267)
• The M55V polymorphism was significantly associated with type 1 diabetes in Asian populations . (PMID:16306380)
• results indicate that the small ubiquitin-like protein 4(SUMO4) is a more common autoimmune disease gene and a supplementary risk factor to type 1 diabetes (PMID:16735488)
• SUMO4 SNP did not significantly influence predisposition to and features of rheumatoid artritis, in contrast to previous genetic and functional evidence that suggested its involvement. (PMID:16755651)
• Genetic and functional evidence is provided supporting SUMO4 as a type 1 diabetes mellitus susceptibility gene. (PMID:17130563)
• No significant association was found between SUMO4 M55V and LADA. (PMID:17130565)
• SUMO4 gene methionine-valine variant is associated with severity of diabetic nephropathy in patients with type 2 diabetes. (PMID:17229939)
• Our results show that Asian-Indians with T1DM are different from other Asian populations. Asian-Indians show more similarity to Caucasians with respect to the association of SUMO4 M55V variant in T1DM. (PMID:17373940)
• contribution of the SUMO4 Met55Val polymorphism to both type 1 and type 2 diabetes susceptibility in the Japanese population (PMID:17374705)
• SUMO4 protein appears to be either in extremely low abundance in human kidney or HEK293 cells or it is not present at all.It remains possible that SUMO4 protein is more abundant in other cell types or can be induced by hormonal or environmental challenges (PMID:17459725)
• we conclude that SUMO4 M55V is associated with type I diabetes melitus in association with high-risk HLA-DR3 and DR4, but not by itself. (PMID:17554341)
• study of the prevalence of four polymorphisms,CTLA-4 -318 C/T, 159 C/T, 3’ STR and SUMO4 163 AG in latent autoimmune diabetes in adults; no association with either of the polymorphisms has been found (PMID:17558709)
• reported a positive association of the SUMO4 M55V variant with diabetic nephropathy in an Asian cohort of 430 patients with type 2 diabetes (PMID:17660269)
• data indicate that the M55V polymorphism in the small ubiquitin-like protein 4(SUMO4) gene is associated with a reduced risk of diabetic retinopathy in type 1 diabetes (PMID:17926234)
• we will update the genetic evidence supporting SUMO4 as a T1D susceptibility gene and discuss the possible explanations for the discrepant associations observed in Caucasians vs Asians.[review] (PMID:17990297)
• no associations of the SUMO4 rs237025 A>G polymorphism with the susceptibility of psoriasis were detected. (PMID:18330586)
• SUMO4 +438 C allele is associated with susceptibility to Behcet’s Disease (BD) in HLA-B51 negative Chinese Han patients, while the AGAT haplotype is protectively associated with BD in HLA-B51 negative patients (PMID:18657476)
• These data not only confirmed previously published data, but also provided additional evidence suggesting a role for SUMO4 sumoylation in the regulation of intracellular stress. (PMID:18708028)
• This study examines whether small ubiquitin-like modifier 4 (SUMO4) polymorphisms were associated with Vogt-Koyanagi-Harada (VKH) syndrome in the Chinese Han population. (PMID:19122825)
• SUMO4 may act as a negative feedback regulator to prevent excessive activation of NFkappaB. (PMID:19222990)
• Association of the polymorphism of SUMO4 with risk of coronary heart disease in type 2 diabetes is suggested. (PMID:19410319)
• This study suggests that in Taiwan the SUMO4 Met 55Val polymorphism is associated with susceptibility to T2DM and Type 2 diabetic patients with GG genotype have worse glycemic control. (PMID:19915388)
• total of 2317 families were genotyped for 15 SNPs in the SUMO4 region. (PMID:19956095)
• The SUMO4 gene single nucleotide polymorphism variant is not associated with susceptibility of the type 2 diabetes polymorphism. (PMID:20728233)
• SUMO4 gene polymorphisms may be involved in the development of skin lesions, vascular Behcet’s disease, as well as the severity of the disease. (PMID:20868570)
• SUMO4 gene M55V variant is associated with the genetic susceptibility of type 1 diabetes mellitus (T1D) in Chinese children. (PMID:21158221)
• SUMO4 Met55Val variant was associated with increased insulin resistance in Chinese patients with newly diagnosed type 2 diabetes. (PMID:21671169)
• The C438T polymorphism in the SUMO4 gene is associated with significantly increased risk of papulopustular skin lesions in HLA-B51-positive Behcet’s disease patients. (PMID:21901353)
• Letter: report SUMO4 polymorphisms associated with protective effect in Tunisian rheumatoid arthritis patients. (PMID:21906435)
• the association between small ubiquitin-like modifier 4 (SUMO4) gene polymorphisms and type 2 diabetes mellitus (PMID:22425950)
• This meta-analysis indicates that the SUMO4 M55V polymorphism confers susceptibility to type I diabetes in Asians and Europeans. (PMID:22884980)
• study demonstrates significant associations of SUMO4 M55V polymorphism with type 1 diabetes mellitus in Asian and Caucasian population and with type 2 diabetes mellitus in Asian population (PMID:22936652)
• No association between SUMO4 gene polymorphisms and acoronary artery disease with and without type 2 diabetes mellitus. (PMID:23042402)
• SUMO4 M55V polymorphism and type-2 diabetes were significantly associated with a possible SUMO4 region to type-2 diabetes susceptibility. (PMID:25189908)
• study suggests that SUMO4 c.163 G to A polymorphism is associated with the susceptibility to diabetic nephropathy in north Indian subjects with type 2 diabetes (PMID:27055882)
• meta-analysis demonstrated that the G allele of the SUMO4 M55V polymorphism could be a susceptible risk locus to type 2 diabetes mellitus, mainly in the Chinese population, while the association in other ethnic population needs to be further validated (PMID:28494838)
• Results show that SUMO-4 is expressed in normal placental development. SUMO-4 expression was increased in pre-eclamptic placentas and in models of oxidative stress and hypoxic injury suggesting that SUMO-4 hyper-SUMOylation may be a potential post-translational mechanism in the stressed pre-eclamptic placenta. (PMID:28545138)
• Both donor and recipient SUMO4 rs237025 polymorphisms contribute to the development of new-onset diabetes mellitus after liver transplantation. (PMID:28689037)
• Donor SUMO4 rs237025 genetic variant was associated with higher tacrolimus C/D ratios in the early period after liver transplantation, which might be related to the down-regulation of CYP3A5 enzyme through the NF-kB signalling pathway. (PMID:28941036)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
drosophila_melanogaster	Sumo	FBGN0264922

Paralogs (3): NFATC2IP (ENSG00000176953), SUMO3 (ENSG00000184900), SUMO2 (ENSG00000188612)

Protein

Protein identifiers

Small ubiquitin-related modifier 4 — Q6EEV6 (reviewed: Q6EEV6)

Alternative names: Small ubiquitin-like protein 4

All UniProt accessions (1): Q6EEV6

UniProt curated annotations — full annotation on UniProt →

Function. Ubiquitin-like protein which can be covalently attached to target lysines as a monomer. Does not seem to be involved in protein degradation and may modulate protein subcellular localization, stability or activity. Upon oxidative stress, conjugates to various anti-oxidant enzymes, chaperones, and stress defense proteins. May also conjugate to NFKBIA, TFAP2A and FOS, negatively regulating their transcriptional activity, and to NR3C1, positively regulating its transcriptional activity. Covalent attachment to its substrates requires prior activation by the E1 complex SAE1-SAE2 and linkage to the E2 enzyme UBE2I.

Subunit / interactions. Interacts with SAE2. Covalently attached to a number of proteins.

Tissue specificity. Expressed mainly in adult and embryonic kidney. Expressed at various levels in immune tissues, with the highest expression in the lymph node and spleen.

Post-translational modifications. In contrast to SUMO1, SUMO2 and SUMO3, seems to be insensitive to sentrin-specific proteases due to the presence of Pro-90. This may impair processing to mature form and conjugation to substrates.

Disease relevance. Type 1 diabetes mellitus 5 (T1D5) [MIM:600320] A form of diabetes mellitus, a multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical features are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. Disease susceptibility may be associated with variants affecting the gene represented in this entry. Valine at position 55 results in greater NFKB1 transcriptional activity and IL12B expression and may be associated with susceptibility to insulin-dependent diabetes mellitus.

Similarity. Belongs to the ubiquitin family. SUMO subfamily.

RefSeq proteins (1): NP_001002255* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000626	Ubiquitin-like_dom	Domain
IPR022617	Rad60/SUMO-like_dom	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily

Pfam: PF11976

UniProt features (5 total): chain 1, propeptide 1, domain 1, cross-link 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6EEV6-F1	82.01	0.54

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 93

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 88 (showing top): GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, CAGCTG_AP4_Q5, GOBP_POSITIVE_REGULATION_OF_BINDING, chr6q25, GOBP_PEPTIDYL_LYSINE_MODIFICATION, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, WATANABE_RECTAL_CANCER_RADIOTHERAPY_RESPONSIVE_UP, ATF1_Q6, GOBP_PROTEIN_SUMOYLATION, GOBP_NEGATIVE_REGULATION_OF_MOLECULAR_FUNCTION, AAAGGGA_MIR204_MIR211, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, SCHLOSSER_SERUM_RESPONSE_DN, HFH1_01, AACTTT_UNKNOWN

GO Biological Process (7): protein sumoylation (GO:0016925), cellular response to oxidative stress (GO:0034599), regulation of canonical NF-kappaB signal transduction (GO:0043122), positive regulation of DNA binding (GO:0043388), negative regulation of DNA binding (GO:0043392), negative regulation of DNA-templated transcription (GO:0045892), regulation of protein localization to nucleus (GO:1900180)

GO Molecular Function (3): protein tag activity (GO:0031386), ubiquitin-like protein ligase binding (GO:0044389), protein binding (GO:0005515)

GO Cellular Component (2): nucleus (GO:0005634), SUMO ligase complex (GO:0106068)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA binding	2
regulation of DNA binding	2
peptidyl-lysine modification	1
protein modification by small protein conjugation	1
response to oxidative stress	1
cellular response to chemical stress	1
canonical NF-kappaB signal transduction	1
regulation of intracellular signal transduction	1
positive regulation of binding	1
negative regulation of binding	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
regulation of protein localization	1
protein localization to nucleus	1
molecular tag activity	1
enzyme binding	1
binding	1
intracellular membrane-bounded organelle	1
transferase complex	1

Protein interactions and networks

STRING

2566 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SUMO4	UBE2I	P50550	954
SUMO4	RAD18	Q9NS91	819
SUMO4	UBE2V2	Q15819	806
SUMO4	SAE1	Q9UBE0	759
SUMO4	UBE2N	P61088	725
SUMO4	SENP1	Q9P0U3	698
SUMO4	UBA2	Q9UBT2	697
SUMO4	RAD52	P43351	659
SUMO4	SENP3	Q9H4L4	645
SUMO4	NEDD8	Q15843	625
SUMO4	SENP5	Q96HI0	622
SUMO4	RANBP2	P49792	612
SUMO4	PIAS1	O75925	611
SUMO4	PIAS2	O75928	611
SUMO4	KLF5	Q13887	605

IntAct

8 interactions, top by confidence:

A	B	Type	Score
MED20	MED19	psi-mi:“MI:0914”(association)	0.840
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	CNOT1	psi-mi:“MI:0914”(association)	0.480
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
VCP	SHTN1	psi-mi:“MI:0914”(association)	0.350
VCP	FAM171A2	psi-mi:“MI:0914”(association)	0.350

BioGRID (20): SUMO4 (Co-fractionation), SUMO4 (Co-fractionation), SUMO4 (Co-fractionation), SUMO4 (Co-fractionation), SUMO4 (Co-fractionation), SUMO4 (Affinity Capture-MS), SUMO4 (Affinity Capture-MS), NFKBIA (Two-hybrid), NFKBIA (Affinity Capture-Western), SUMO4 (Affinity Capture-MS), SUMO4 (Affinity Capture-MS), SUMO4 (Positive Genetic), SUMO4 (Affinity Capture-MS), SUMO4 (Proximity Label-MS), SUMO4 (Affinity Capture-MS)

ESM2 similar proteins: A7WLH8, A7WLI0, B3H5R8, G2XKQ0, O13351, O57686, P29504, P55852, P55853, P55854, P55857, P61955, P61956, P61957, P61958, P61959, P62982, P62983, P63165, P63166, Q12306, Q17QV3, Q28H04, Q2EF74, Q2PFW2, Q3E8A8, Q5E9D1, Q5EAX4, Q5I0H3, Q5R6J4, Q5XIF4, Q5ZHQ1, Q5ZJM9, Q6DEP7, Q6DHL4, Q6DI05, Q6DK72, Q6EEV6, Q6GPW2, Q6LDZ8

Diamond homologs: A7WLH8, A7WLI0, B3H5R8, G2XKQ0, O13351, O57686, P55852, P55853, P55854, P55857, P61955, P61956, P61957, P61958, P61959, P63165, P63166, Q0P4K8, Q12306, Q17QV3, Q28H04, Q2EF74, Q2PFW2, Q5E9D1, Q5EAX4, Q5I0H3, Q5R6J4, Q5XIF4, Q5ZHQ1, Q5ZJM9, Q6DEP7, Q6DHL4, Q6DI05, Q6DK72, Q6EEV6, Q6GPW2, Q6LDZ8, Q6NV25, Q7SZ22, Q7SZR5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

22 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	15
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1460458	NC_000006.11:g.(?149691134)(149730855_?)del	Pathogenic

SpliceAI

317 predictions. Top by Δscore:

Variant	Effect	Δscore
6:149400457:G:GA	donor_gain	0.9600
6:149400456:T:TA	donor_gain	0.9400
6:149400685:G:T	donor_gain	0.9200
6:149400788:G:GG	donor_gain	0.9100
6:149400666:G:T	donor_gain	0.8700
6:149400787:A:AG	donor_gain	0.8400
6:149400790:AT:A	donor_gain	0.8200
6:149400305:T:A	acceptor_gain	0.8100
6:149400481:GC:G	donor_gain	0.7900
6:149400666:G:GT	donor_gain	0.7900
6:149400467:G:GT	donor_gain	0.7700
6:149400317:T:A	acceptor_gain	0.7200
6:149400369:C:G	donor_gain	0.7200
6:149400673:C:G	donor_gain	0.7000
6:149400416:G:GT	donor_gain	0.6700
6:149400314:T:A	acceptor_gain	0.6400
6:149400626:G:GT	donor_gain	0.6300
6:149400543:G:A	acceptor_gain	0.5900
6:149400984:C:T	donor_gain	0.5800
6:149400331:T:G	donor_gain	0.5600
6:149400542:C:CA	acceptor_gain	0.5600
6:149400420:TC:T	donor_gain	0.5500
6:149400684:G:GT	donor_gain	0.5500
6:149400413:G:GT	donor_gain	0.5400
6:149401016:G:GG	donor_gain	0.5400
6:149400302:T:TA	acceptor_gain	0.5200
6:149400416:GAA:G	donor_gain	0.5200
6:149400426:C:G	donor_gain	0.5200
6:149400303:G:GA	acceptor_gain	0.5100
6:149400632:G:GT	donor_gain	0.5100

AlphaMissense

626 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:149400485:T:C	F32L	0.929
6:149400487:T:A	F32L	0.929
6:149400487:T:G	F32L	0.929
6:149400569:T:C	F60L	0.913
6:149400571:C:A	F60L	0.913
6:149400571:C:G	F60L	0.913
6:149400575:T:C	F62L	0.873
6:149400577:T:A	F62L	0.873
6:149400577:T:G	F62L	0.873
6:149400650:T:C	F87L	0.847
6:149400652:T:A	F87L	0.847
6:149400652:T:G	F87L	0.847
6:149400486:T:C	F32S	0.739
6:149400570:T:C	F60S	0.729
6:149400450:T:C	L20S	0.723
6:149400490:G:C	K33N	0.649
6:149400490:G:T	K33N	0.649
6:149400523:G:A	M44I	0.630
6:149400523:G:C	M44I	0.630
6:149400523:G:T	M44I	0.630
6:149400522:T:C	M44T	0.626
6:149400570:T:G	F60C	0.616
6:149400496:G:C	K35N	0.614
6:149400496:G:T	K35N	0.614
6:149400624:T:C	M78T	0.597
6:149400517:A:C	K42N	0.591
6:149400517:A:T	K42N	0.591

dbSNP variants (sampled 300 via entrez): RS1000725887 (6:149399832 T>G), RS1000954908 (6:149401430 A>G,T), RS1004064088 (6:149399382 T>A,C), RS1005286707 (6:149399468 G>A), RS1006176676 (6:149401740 A>G), RS1006814775 (6:149399083 T>C), RS1007796508 (6:149399780 G>T), RS1008135193 (6:149400964 C>A), RS1009256033 (6:149401458 G>A), RS1009308742 (6:149401757 T>C), RS1009968535 (6:149401242 G>A), RS1010019502 (6:149400939 A>G), RS1011637781 (6:149399272 G>T), RS1013323486 (6:149399449 G>A,T), RS1014277874 (6:149400870 A>G)

Disease associations

OMIM: gene MIM:608829 | disease phenotypes: MIM:222100, MIM:600320

GenCC curated gene-disease

Disease	Classification	Inheritance
type 1 diabetes mellitus 5	Limited	Autosomal dominant

Mondo (2): type 1 diabetes mellitus (MONDO:0005147), type 1 diabetes mellitus 5 (MONDO:0010863)

Orphanet (1): NON RARE IN EUROPE: Diabetes mellitus type 1 (Orphanet:243377)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST004858_4	Dupuytren’s disease	1.000000e-17

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004229	Dupuytren Contracture

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D003922	Diabetes Mellitus, Type 1	C18.452.394.750.124; C19.246.267; C20.111.327
C563958	Diabetes Mellitus, Insulin-Dependent, 5 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs237025	Metabolism/PK	3	tacrolimus	Liver transplantation

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs237025	SUMO4, TAB2	3	1.00	1	tacrolimus
rs237024	SUMO4, TAB2		0.00	0

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects expression, increases abundance, decreases expression	3
Benzo(a)pyrene	decreases expression, increases expression	3
Particulate Matter	decreases expression, increases abundance	2
potassium chromate(VI)	affects cotreatment, increases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
licochalcone B	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Capsaicin	increases expression	1
Ozone	affects expression, increases abundance	1
Plant Extracts	increases expression, affects cotreatment	1
Valproic Acid	decreases expression	1
Aflatoxin B1	affects expression	1
Lactic Acid	increases expression	1

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00145353	PHASE4	UNKNOWN	Insulin NovoRapid Versus Actrapid in Treatment of Type 1 Diabetic Patients During Daily Adjustment of Insulin Dose
NCT00145379	PHASE4	COMPLETED	The Effect of Metformin in Overweight Patients With Dysregulated Type 1 Diabetes Mellitus
NCT00206401	PHASE4	COMPLETED	Lantus in the Treatment of Type 1 Diabetes Children
NCT00276393	PHASE4	COMPLETED	Treatment Trial Evaluating Long Acting Insulin in Type 1 Diabetes
NCT00291772	PHASE4	COMPLETED	Continuous Subcutaneous Infusion of Pramlintide and Insulin
NCT00315952	PHASE4	COMPLETED	Study to Estimate the Effects of Inhaled Versus Intravenous (IV) Infusion of Human Insulin in Subjects With Type 1 Diabetes
NCT00340613	PHASE4	COMPLETED	Lunch Time Insulin Injection by School Nurse for Poorly Controlled Diabetes
NCT00346996	PHASE4	COMPLETED	Insulin Analogues and Severe Hypoglycaemia
NCT00360984	PHASE4	COMPLETED	Prevention of Severe Hypoglycemia in Type 1 Diabetes
NCT00372086	PHASE4	COMPLETED	Rosiglitazone and Insulin in T1DM Adolescents
NCT00442767	PHASE4	COMPLETED	Post-meal Insulin Dosing With Adjuvant Pre-meal Pramlintide in Children With Type 1 Diabetes Mellitus
NCT00453934	PHASE4	TERMINATED	Patient Preference of h-Patch vs. Pen or Needle/Syringe as Insulin Administration Device
NCT00461331	PHASE4	COMPLETED	Comparison of Insulins Aspart and Lispro in Insulin Pumps
NCT00472875	PHASE4	UNKNOWN	Do Sulphonylureas Preserve Cortical Function During Hypoglycaemia?
NCT00497536	PHASE4	COMPLETED	Pharmacokinetics of IAsp Following CSII in Patients With T1DM
NCT00502138	PHASE4	COMPLETED	A Pilot Study of Continuous Subcutaneous Pramlintide Infusion Therapy in Patients With Type 1 Diabetes
NCT00505882	PHASE4	WITHDRAWN	Efficacy of Pramlintide on Prevention of Weight Gain Early Onset of Type 1 Diabetes
NCT00530023	PHASE4	COMPLETED	Feasibility Study for Training Pump Naïve Subjects To Use The Paradigm® System And Evaluate Effectiveness
NCT00542399	PHASE4	COMPLETED	Comparing the Metabolic Control of Once to Twice-daily Insulin Detemir Injections
NCT00564395	PHASE4	COMPLETED	Detemir: Role in Type 1 Diabetes
NCT00814476	PHASE4	COMPLETED	The Effects of Regular Home Use Vs Diabetic Team- Supported Use of the Medtronic CareLink Therapy Management System.
NCT00898534	PHASE4	COMPLETED	Effect of Immediate Hemoglobin A1c on Glycemic Control in Children With Type I Diabetes Mellitus
NCT00913497	PHASE4	COMPLETED	The Effect of Insulin Glulisine Compared With Insulin Aspart on Breakfast Post Prandial Glucose Levels in Prepubertal Children
NCT00978796	PHASE4	COMPLETED	Assessing Glucose Effects of Sitagliptin (Januvia) in Adult Patients With Type 1 Diabetes
NCT01019486	PHASE4	COMPLETED	Regadenoson Blood Flow in Type 1 Diabetes (RABIT1D)
NCT01235819	PHASE4	COMPLETED	Comparison Between GLP 1 Analogues and DPP 4 Inhibitors in Type 1 Diabetes Mellitus
NCT01269034	PHASE4	COMPLETED	New Onset Type 1 Diabetes: Role of Exenatide
NCT01269047	PHASE4	COMPLETED	Use of Exenatide and Pramlintide to Decrease Post-prandial Hyperglycemia
NCT01280682	PHASE4	COMPLETED	Immune Intervention With Rituximab to Preserve Beta Cell Function in Early Onset Type 1 Diabetes
NCT01331343	PHASE4	COMPLETED	Effectiveness Study of the Guardian RT in Type 1 Diabetics
NCT01351857	PHASE4	COMPLETED	Diabetes Care Management Compared to Standard Diabetes Care in Adolescents and Young Adults With Type 1 Diabetes
NCT01390480	PHASE4	COMPLETED	Effects of Vitamin D Supplementation in Subjects With New Onset of Type 1 Diabetes
NCT01400659	PHASE4	COMPLETED	Pizza-Salami Study in Children and Adolescents With Type 1 Diabetes
NCT01454700	PHASE4	COMPLETED	Effect of CSII and CGM on Progression of Late Diabetic Complications
NCT01488136	PHASE4	COMPLETED	Use of Diazoxide in Acute Hypoglycaemia
NCT01497912	PHASE4	COMPLETED	Treatment Effects of Atorvastatin on Hemostasis and Skin Microcirculation in Patients With Type 1 Diabetes
NCT01526733	PHASE4	COMPLETED	Randomized, Double Blind, 2 Way Crossover Study of CSII With, Versus Without, Pretreatment With Human Hyaluronidase
NCT01668485	PHASE4	COMPLETED	Mechanisms of Glucose Counterregulation in Pancreatic Islet Transplantation
NCT01678235	PHASE4	COMPLETED	Insulin Glulisine and Aspart in Postprandial Glycemic Control After High-GI Meal in Children With Type 1 Diabetes Mellitus
NCT01718093	PHASE4	COMPLETED	A Pilot Study to Assess the Glucose Lowering Effect of Metformin and Sitagliptin in Adolescents With Type 1 Diabetes