SIMC1

Summary

SIMC1 (SUMO interacting motifs containing 1, HGNC:24779) is a protein-coding gene on chromosome 5q35.2, encoding SUMO-interacting motif-containing protein 1 (Q8NDZ2). Plays a role in SMC5-SMC6 complex recruitment for viral restriction.

Enables SUMO polymer binding activity and peptidase inhibitor activity. Located in PML body and sarcomere.

Source: NCBI Gene 375484 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 90 total
• MANE Select transcript: NM_001308195

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24779
Approved symbol	SIMC1
Name	SUMO interacting motifs containing 1
Location	5q35.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ44216, OOMA1, PLEIAD
Ensembl gene	ENSG00000170085
Ensembl biotype	protein_coding
OMIM	618102
Entrez	375484

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 13 protein_coding, 4 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000332772, ENST00000341199, ENST00000429602, ENST00000430704, ENST00000443967, ENST00000467472, ENST00000481515, ENST00000495423, ENST00000503595, ENST00000508769, ENST00000514128, ENST00000881279, ENST00000938812, ENST00000938813, ENST00000938814, ENST00000943631, ENST00000943632, ENST00000943633, ENST00000943634

RefSeq mRNA: 4 — MANE Select: NM_001308195 NM_001308195, NM_001308196, NM_001308200, NM_198567

CCDS: CCDS4398, CCDS78088, CCDS78089, CCDS78090

Canonical transcript exons

ENST00000429602 — 10 exons

Exon	Start	End
ENSE00002262057	176238424	176238637
ENSE00003467970	176313691	176313845
ENSE00003509417	176295030	176295262
ENSE00003888955	176289654	176290955
ENSE00003889084	176322273	176322425
ENSE00003889916	176337062	176337146
ENSE00003891189	176336720	176336876
ENSE00003892985	176345183	176345989
ENSE00003895041	176296251	176296320
ENSE00003895274	176324629	176324757

Expression profiles

Bgee: expression breadth ubiquitous, 246 present calls, max score 93.12.

FANTOM5 (CAGE): breadth broad, TPM avg 1.5373 / max 40.9090, expressed in 828 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
60398	1.4916	827
60399	0.0303	3
60401	0.0109	3
60400	0.0043	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	93.12	gold quality
left ovary	UBERON:0002119	92.91	gold quality
adrenal tissue	UBERON:0018303	91.97	gold quality
ovary	UBERON:0000992	91.71	gold quality
right ovary	UBERON:0002118	91.55	gold quality
right adrenal gland	UBERON:0001233	90.72	gold quality
right adrenal gland cortex	UBERON:0035827	90.16	gold quality
adrenal gland	UBERON:0002369	89.56	gold quality
adrenal cortex	UBERON:0001235	89.47	gold quality
left adrenal gland	UBERON:0001234	89.20	gold quality
left testis	UBERON:0004533	89.16	gold quality
adult organism	UBERON:0007023	89.10	gold quality
testis	UBERON:0000473	89.06	gold quality
oviduct epithelium	UBERON:0004804	89.02	gold quality
right testis	UBERON:0004534	88.98	gold quality
left adrenal gland cortex	UBERON:0035825	88.91	gold quality
decidua	UBERON:0002450	88.53	gold quality
mucosa of stomach	UBERON:0001199	87.94	gold quality
cortical plate	UBERON:0005343	86.68	gold quality
fallopian tube	UBERON:0003889	86.08	gold quality
urethra	UBERON:0000057	85.52	gold quality
cardia of stomach	UBERON:0001162	85.21	gold quality
germinal epithelium of ovary	UBERON:0001304	84.79	gold quality
adenohypophysis	UBERON:0002196	84.79	gold quality
pituitary gland	UBERON:0000007	84.73	gold quality
ganglionic eminence	UBERON:0004023	84.45	gold quality
epithelial cell of pancreas	CL:0000083	84.22	silver quality
secondary oocyte	CL:0000655	84.04	gold quality
mucosa of paranasal sinus	UBERON:0005030	83.90	gold quality
ventricular zone	UBERON:0003053	83.80	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.46

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

43 targeting SIMC1, 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-5692A	100.00	74.40	6850
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-657	99.48	66.02	848
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-133A-3P	99.27	71.53	1270
HSA-MIR-133B	99.27	71.53	1270
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-548L	99.06	70.90	2560
HSA-MIR-922	99.02	67.23	1838
HSA-MIR-4742-5P	98.89	68.41	1542
HSA-MIR-3145-3P	98.85	69.07	2031
HSA-MIR-4303	98.01	68.13	2304

Literature-anchored findings (GeneRIF, showing 1)

• Authors found that PLEIAD also interacts with CTBP1 (C-terminal binding protein 1), a transcriptional co-regulator, and CTBP1 is proteolyzed in COS7 cells expressing CAPN3. (PMID:23707407)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	simc1	ENSDARG00000098209
mus_musculus	Simc1	ENSMUSG00000043183
rattus_norvegicus	Simc1	ENSRNOG00000016932

Paralogs (2): SKIDA1 (ENSG00000180592), EPOP (ENSG00000273604)

Protein

Protein identifiers

SUMO-interacting motif-containing protein 1 — Q8NDZ2 (reviewed: Q8NDZ2)

Alternative names: Platform element for inhibition of autolytic degradation

All UniProt accessions (1): Q8NDZ2

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in SMC5-SMC6 complex recruitment for viral restriction. Forms a complex with SLF2 and this complex is required to recruit SMC5-SMC6 complex to PML nuclear bodies and sites of viral replication. Inhibits the protease activity of CAPN3. Inhibits the protease activity of CAPN3.

Subunit / interactions. Forms a heterodimer with SLF2. Interacts with SMC6 and ZNF451. Interacts (via SIM domains) with SUMO1 and SUMO2. Interacts with CAPN3 and CTBP1. Interacts with CAPN3 and CTBP1.

Subcellular location. Nucleus. PML body Cytoplasm. Cytoplasm. Myofibril. Sarcomere.

Tissue specificity. Skeletal muscle.

Isoforms (5)

UniProt ID	Names	Canonical?
Q8NDZ2-1	1, PLEIADa	yes
Q8NDZ2-2	2
Q8NDZ2-3	3
Q8NDZ2-4	4
Q8NDZ2-5	5, PLEIADf

RefSeq proteins (4): NP_001295124, NP_001295125, NP_001295129, NP_940969 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR052119	ElonginBC-PRC2_ViralRestrict	Family

UniProt features (59 total): helix 21, splice variant 8, region of interest 7, compositionally biased region 5, sequence variant 4, mutagenesis site 4, sequence conflict 3, turn 3, short sequence motif 2, chain 1, strand 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7T5P	ELECTRON MICROSCOPY	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NDZ2-F1	59.59	0.29

Functional residue map

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

Mutagenesis-validated functional residues (4):

Position	Phenotype
473	loss of interaction with smc6; when associated with a-477, k-480 and k-481.
477	loss of interaction with smc6; when associated with d-473, k-480 and k-481.
480	loss of interaction with smc6; when associated with d-473, a-477 and k-481.
481	loss of interaction with smc6; when associated with d-473, a-477 and k-480.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 82 (showing top): ATACCTC_MIR202, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, ACEVEDO_LIVER_CANCER_UP, GOCC_NUCLEAR_BODY, GOCC_PML_BODY, GOMF_PEPTIDASE_REGULATOR_ACTIVITY, GOMF_UBIQUITIN_LIKE_PROTEIN_BINDING, GOMF_SUMO_BINDING, GOMF_ENZYME_INHIBITOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, CHICAS_RB1_TARGETS_SENESCENT, LEE_BMP2_TARGETS_DN, PURBEY_TARGETS_OF_CTBP1_NOT_SATB1_UP, LIM_MAMMARY_STEM_CELL_UP, GOCC_SUPRAMOLECULAR_COMPLEX

GO Biological Process (0):

GO Molecular Function (3): peptidase inhibitor activity (GO:0030414), SUMO polymer binding (GO:0032184), protein binding (GO:0005515)

GO Cellular Component (4): cytoplasm (GO:0005737), PML body (GO:0016605), sarcomere (GO:0030017), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
enzyme inhibitor activity	1
peptidase activity	1
peptidase regulator activity	1
SUMO binding	1
binding	1
intracellular anatomical structure	1
nuclear body	1
myofibril	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

780 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SIMC1	CAPN3	P20807	627
SIMC1	RNF111	Q6ZNA4	541
SIMC1	FAM153B	P0C7A2	479
SIMC1	UBE2I	P50550	457
SIMC1	RAB24	Q969Q5	439
SIMC1	MC2R	Q01718	420
SIMC1	OR2T34	Q8NGX1	418
SIMC1	GNS	P15586	407
SIMC1	NOP16	Q9Y3C1	399
SIMC1	ZNF354B	Q96LW1	398
SIMC1	SOBP	A7XYQ1	390
SIMC1	GFUS	Q13630	390
SIMC1	WDR55	Q9H6Y2	348
SIMC1	KIAA1586	Q9HCI6	348
SIMC1	RNF4	P78317	348

IntAct

56 interactions, top by confidence:

A	B	Type	Score
SMC6	SMC5	psi-mi:“MI:0914”(association)	0.860
DNAJB11	HSPA5	psi-mi:“MI:0914”(association)	0.830
SLF1	SLF2	psi-mi:“MI:0914”(association)	0.780
SLF2	SIMC1	psi-mi:“MI:0403”(colocalization)	0.750
SLF2	SIMC1	psi-mi:“MI:0915”(physical association)	0.750
SLF2	SIMC1	psi-mi:“MI:0407”(direct interaction)	0.750
SIMC1	SLF2	psi-mi:“MI:0914”(association)	0.750
DNAJB11	SIMC1	psi-mi:“MI:0915”(physical association)	0.660
TUBB3	POTEF	psi-mi:“MI:0914”(association)	0.530
NPY2R	RTL8C	psi-mi:“MI:0914”(association)	0.530
KBTBD4	KPNA5	psi-mi:“MI:0914”(association)	0.530
SDF4	GTPBP6	psi-mi:“MI:0914”(association)	0.530
NSMCE1	PMF1	psi-mi:“MI:0914”(association)	0.530
ZNF451	SIMC1	psi-mi:“MI:0915”(physical association)	0.490
SIMC1	CSNK2B	psi-mi:“MI:0915”(physical association)	0.370
PLK1	SIMC1	psi-mi:“MI:0915”(physical association)	0.370
TUBA1A	KIF2A	psi-mi:“MI:0914”(association)	0.350
C5AR2	ILVBL	psi-mi:“MI:0914”(association)	0.350
RFPL4B	KRBA1	psi-mi:“MI:0914”(association)	0.350
IL17RA	DDX11L8	psi-mi:“MI:0914”(association)	0.350
BBS7	PER1	psi-mi:“MI:0914”(association)	0.350
KLHL10	BCL2L11	psi-mi:“MI:0914”(association)	0.350
CSNK2A2	VWA8	psi-mi:“MI:0914”(association)	0.350

BioGRID (68): SUMO2 (Reconstituted Complex), SIMC1 (Affinity Capture-MS), SIMC1 (Affinity Capture-MS), SIMC1 (Affinity Capture-MS), SIMC1 (Affinity Capture-MS), SIMC1 (Affinity Capture-MS), SIMC1 (Affinity Capture-MS), SIMC1 (Affinity Capture-MS), SIMC1 (Affinity Capture-MS), SIMC1 (Affinity Capture-MS), SIMC1 (Affinity Capture-MS), SIMC1 (Affinity Capture-MS), SIMC1 (Affinity Capture-MS), SIMC1 (Affinity Capture-MS), SIMC1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0M3U1B0, A1A5Q6, A2AFS9, A2AVR2, A2CI98, A2CJ06, A2RTY3, A2RUW0, O70167, O70173, P0C2Y1, P15304, P59729, Q08EC4, Q3SYK4, Q3TYG6, Q3U1D0, Q4R744, Q4R9E9, Q5R4B2, Q5T4T6, Q5TGP6, Q5VWK0, Q68CQ1, Q6AYJ3, Q6IFT4, Q6IRU7, Q6REY9, Q6ZUA9, Q7Z572, Q80VH0, Q86WZ0, Q86XG9, Q8C0X8, Q8CCC3, Q8ND61, Q8NDZ2, Q8TB24, Q96M43, Q96QP1

Diamond homologs: E9Q6E9, F1LWT0, Q8NDZ2

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 66 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
SUMOylation of DNA damage response and repair proteins	5	18.8×	3e-04
Interferon Signaling	5	15.4×	5e-04
Recruitment of NuMA to mitotic centrosomes	5	14.9×	5e-04
EML4 and NUDC in mitotic spindle formation	6	14.3×	2e-04
RHO GTPases Activate Formins	7	13.9×	1e-04
Cilium Assembly	5	13.9×	6e-04
Resolution of Sister Chromatid Cohesion	6	13.3×	3e-04
Mitotic Prometaphase	7	12.4×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
regulation of telomere maintenance	6	88.7×	7e-09
protein sumoylation	8	45.5×	2e-09
double-strand break repair via homologous recombination	6	16.4×	2e-04
DNA damage response	7	6.6×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	74
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2216 predictions. Top by Δscore:

Variant	Effect	Δscore
5:176295231:G:GT	donor_gain	1.0000
5:176295234:GCC:G	donor_gain	1.0000
5:176295263:G:GG	donor_gain	1.0000
5:176295317:GGCA:G	donor_gain	1.0000
5:176313685:CCACA:C	acceptor_loss	1.0000
5:176313686:CACAG:C	acceptor_loss	1.0000
5:176313687:ACAG:A	acceptor_gain	1.0000
5:176313688:CA:C	acceptor_loss	1.0000
5:176313689:A:AG	acceptor_gain	1.0000
5:176313689:A:C	acceptor_loss	1.0000
5:176313689:AG:A	acceptor_gain	1.0000
5:176313689:AGG:A	acceptor_gain	1.0000
5:176313690:G:A	acceptor_gain	1.0000
5:176313690:G:GG	acceptor_gain	1.0000
5:176313690:GGG:G	acceptor_gain	1.0000
5:176313690:GGGA:G	acceptor_gain	1.0000
5:176313690:GGGAC:G	acceptor_gain	1.0000
5:176313842:TCAGG:T	donor_gain	1.0000
5:176313843:CAGGT:C	donor_gain	1.0000
5:176313844:AGGT:A	donor_loss	1.0000
5:176313844:AGGTA:A	donor_gain	1.0000
5:176313845:GGTAA:G	donor_gain	1.0000
5:176313846:G:GA	donor_loss	1.0000
5:176313846:GT:G	donor_gain	1.0000
5:176313847:T:A	donor_loss	1.0000
5:176322268:TACA:T	acceptor_loss	1.0000
5:176322271:A:AC	acceptor_loss	1.0000
5:176322271:A:AG	acceptor_gain	1.0000
5:176322271:AG:A	acceptor_gain	1.0000
5:176322271:AGG:A	acceptor_gain	1.0000

AlphaMissense

5797 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:176313743:T:C	L577P	1.000
5:176324655:T:C	L671P	1.000
5:176324664:C:A	A674D	1.000
5:176324685:C:A	P681H	1.000
5:176324693:A:C	S684R	1.000
5:176324695:C:A	S684R	1.000
5:176324695:C:G	S684R	1.000
5:176324709:C:A	A689D	1.000
5:176337108:T:C	L773P	1.000
5:176337117:T:C	L776P	1.000
5:176337125:A:C	S779R	1.000
5:176337127:T:A	S779R	1.000
5:176337127:T:G	S779R	1.000
5:176295055:T:A	I467N	0.999
5:176295124:T:C	F490S	0.999
5:176295127:T:C	L491S	0.999
5:176295132:G:C	D493H	0.999
5:176295135:T:C	F494L	0.999
5:176295137:T:A	F494L	0.999
5:176295137:T:G	F494L	0.999
5:176295157:C:A	P501Q	0.999
5:176295244:T:C	L530P	0.999
5:176295247:T:C	L531P	0.999
5:176296253:T:C	L537P	0.999
5:176296255:C:G	H538D	0.999
5:176296282:T:A	W547R	0.999
5:176296282:T:C	W547R	0.999
5:176296288:T:A	W549R	0.999
5:176296288:T:C	W549R	0.999
5:176313815:T:A	L601H	0.999

dbSNP variants (sampled 300 via entrez): RS1000013784 (5:176294860 G>A,C), RS1000018476 (5:176341136 G>A), RS1000037761 (5:176257641 C>T), RS1000066142 (5:176294627 T>A), RS1000111705 (5:176304343 A>C,G,T), RS1000136070 (5:176319950 C>A), RS1000142855 (5:176304241 A>C,G), RS1000150673 (5:176275110 A>G), RS1000162924 (5:176334995 G>C,T), RS1000167184 (5:176319608 T>C), RS1000209243 (5:176315331 G>T), RS1000230211 (5:176245140 A>G), RS1000257718 (5:176320609 A>G), RS1000299517 (5:176280222 TATCTA>T), RS1000301768 (5:176320132 G>A,C)

Disease associations

OMIM: gene MIM:618102 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008745_52	Estimated glomerular filtration rate in non-diabetics	1.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, decreases methylation, increases expression, affects expression	4
Air Pollutants	affects expression, increases abundance, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	increases expression	1
zinc chromate	decreases expression, increases abundance	1
tobacco tar	increases expression	1
potassium chromate(VI)	increases expression	1
nickel sulfate	increases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
2-palmitoylglycerol	increases expression	1
abrine	decreases expression	1
NSC 689534	affects binding, decreases expression	1
Acetaminophen	increases expression	1
Arsenic	affects methylation	1
Copper	affects binding, decreases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Doxorubicin	decreases expression	1
Ozone	affects expression, increases abundance	1
Tretinoin	decreases expression	1
Vanadates	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cadmium Chloride	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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