SUN3

Summary

SUN3 (Sad1 and UNC84 domain containing 3, HGNC:22429) is a protein-coding gene on chromosome 7p12.3, encoding SUN domain-containing protein 3 (Q8TAQ9). As a probable component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex, involved in the connection between the nuclear lamina and the cytoskeleton.

Predicted to enable protein-membrane adaptor activity. Predicted to be located in nuclear inner membrane. Predicted to be part of meiotic nuclear membrane microtubule tethering complex. Predicted to be active in nuclear envelope.

Source: NCBI Gene 256979 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 48 total
• MANE Select transcript: NM_001030019

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22429
Approved symbol	SUN3
Name	Sad1 and UNC84 domain containing 3
Location	7p12.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC33329
Ensembl gene	ENSG00000164744
Ensembl biotype	protein_coding
OMIM	618984
Entrez	256979

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000297325, ENST00000395572, ENST00000412142, ENST00000412371, ENST00000438771, ENST00000449896, ENST00000453071, ENST00000461953, ENST00000473723

RefSeq mRNA: 3 — MANE Select: NM_001030019 NM_001030019, NM_001284350, NM_152782

CCDS: CCDS34636, CCDS64647

Canonical transcript exons

ENST00000297325 — 10 exons

Exon	Start	End
ENSE00001345150	48028817	48029107
ENSE00003529336	48025877	48025938
ENSE00003549686	48017262	48017365
ENSE00003559756	47987148	47987449
ENSE00003567874	47996031	47996146
ENSE00003576570	47988788	47988880
ENSE00003589171	48007165	48007327
ENSE00003631119	48005969	48006053
ENSE00003677551	47994315	47994482
ENSE00003748474	48009035	48009075

Expression profiles

Bgee: expression breadth ubiquitous, 142 present calls, max score 91.64.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0611 / max 19.3967, expressed in 19 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
84083	0.0247	5
84081	0.0148	7
84080	0.0093	3
84084	0.0071	4
84082	0.0051	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	91.64	gold quality
left testis	UBERON:0004533	91.50	gold quality
sperm	CL:0000019	90.99	gold quality
testis	UBERON:0000473	89.36	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.95	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.44	gold quality
adult organism	UBERON:0007023	73.66	gold quality
buccal mucosa cell	CL:0002336	64.87	gold quality
kidney epithelium	UBERON:0004819	55.17	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
epithelial cell of pancreas	CL:0000083	53.65	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
nucleus accumbens	UBERON:0001882	52.54	gold quality
putamen	UBERON:0001874	52.40	gold quality
caudate nucleus	UBERON:0001873	52.00	gold quality
pancreatic ductal cell	CL:0002079	51.77	silver quality
placenta	UBERON:0001987	50.81	gold quality
Brodmann (1909) area 9	UBERON:0013540	50.71	gold quality
mucosa of transverse colon	UBERON:0004991	50.66	gold quality
hypothalamus	UBERON:0001898	50.59	gold quality
myocardium	UBERON:0002349	50.25	gold quality
anterior cingulate cortex	UBERON:0009835	49.33	gold quality
tibialis anterior	UBERON:0001385	49.26	silver quality
sural nerve	UBERON:0015488	49.09	gold quality
right uterine tube	UBERON:0001302	48.64	gold quality
amygdala	UBERON:0001876	48.27	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	47.88	gold quality
right coronary artery	UBERON:0001625	47.64	gold quality
nasal cavity epithelium	UBERON:0005384	47.49	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.88

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

7 targeting SUN3, 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-1179	99.71	68.70	1040
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-4778-5P	97.96	68.06	1634
HSA-MIR-4638-3P	97.90	65.75	905

Literature-anchored findings (GeneRIF, showing 1)

• cDNA of Macaca fascicularis used to identify a novel human gene, SUNC1. (PMID:12498619)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Sun3	ENSMUSG00000040985
rattus_norvegicus	Sun3	ENSRNOG00000005105
caenorhabditis_elegans		WBGENE00006816

Paralogs (4): SPAG4 (ENSG00000061656), SUN2 (ENSG00000100242), SUN1 (ENSG00000164828), SUN5 (ENSG00000167098)

Protein

Protein identifiers

SUN domain-containing protein 3 — Q8TAQ9 (reviewed: Q8TAQ9)

Alternative names: Sad1/unc-84 domain-containing protein 1

All UniProt accessions (4): Q8TAQ9, F8WDT4, H7BZA7, H7C2N0

UniProt curated annotations — full annotation on UniProt →

Function. As a probable component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex, involved in the connection between the nuclear lamina and the cytoskeleton. The nucleocytoplasmic interactions established by the LINC complex play an important role in the transmission of mechanical forces across the nuclear envelope and in nuclear movement and positioning. May be involved in nuclear remodeling during sperm head formation in spermatogenesis. A probable SUN3:SYNE1 LINC complex may tether spermatid nuclei to posterior cytoskeletal structures such as the manchette.

Subunit / interactions. Self-associates. Interacts with SYNE1 and SPAG4/SUN4. Proposed to form a spermatogenesis-specific LINC complex with SYNE1 during sperm head formation possibly implicating a SUN domain-based heterotrimer with SPAG4/SUN4 associating with SYNE1.

Subcellular location. Membrane. Nucleus envelope. Nucleus inner membrane.

Domain organisation. The short coiled coil domain is proposed to be not involved in load-bearing and force transmission from the cytoskeleton but in mere nucleus anchorage instead.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8TAQ9-1	1	yes
Q8TAQ9-2	2
Q8TAQ9-3	3

RefSeq proteins (3): NP_001025190, NP_001271279, NP_689995 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012919	SUN_dom	Domain
IPR045119	SUN1-5	Family

Pfam: PF07738

UniProt features (13 total): splice variant 3, topological domain 2, sequence variant 2, sequence conflict 2, chain 1, transmembrane region 1, domain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TAQ9-F1	75.92	0.38

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 33 (showing top): SENESE_HDAC3_TARGETS_DN, GOCC_NUCLEAR_ENVELOPE, GOCC_ORGANELLE_INNER_MEMBRANE, GOCC_NUCLEAR_INNER_MEMBRANE, GOCC_MEMBRANE_PROTEIN_COMPLEX, GOCC_NUCLEAR_MEMBRANE, chr7p12, GOCC_ORGANELLE_ENVELOPE, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, GOMF_PROTEIN_MEMBRANE_ADAPTOR_ACTIVITY, GOCC_MICROTUBULE_ORGANIZING_CENTER_ATTACHMENT_SITE, GSE5503_PLN_DC_VS_SPLEEN_DC_ACTIVATED_ALLOGENIC_TCELL_DN, HHEX_TARGET_GENES, MEF2D_TARGET_GENES, PAX7_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (1): protein-membrane adaptor activity (GO:0043495)

GO Cellular Component (5): nuclear envelope (GO:0005635), nuclear inner membrane (GO:0005637), meiotic nuclear membrane microtubule tethering complex (GO:0034993), nucleus (GO:0005634), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein-macromolecule adaptor activity	1
nucleus	1
endomembrane system	1
organelle envelope	1
organelle inner membrane	1
nuclear membrane	1
microtubule organizing center attachment site	1
nuclear membrane microtubule tethering complex	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

744 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SUN3	SYNE1	Q8NF91	813
SUN3	SYNE3	Q6ZMZ3	806
SUN3	SYNE2	Q8WXH0	638
SUN3	ODF1	Q14990	627
SUN3	KASH5	Q8N6L0	625
SUN3	SYNE4	Q8N205	624
SUN3	C7orf57	Q8NEG2	570
SUN3	EMD	P50402	567
SUN3	SPMAP2L	P0DJG4	528
SUN3	SEPTIN12	Q8IYM1	509
SUN3	SUN5	Q8TC36	486
SUN3	IRAG2	Q12912	481
SUN3	PLEC	Q15149	473
SUN3	HOOK1	Q9UJC3	459
SUN3	NRM	Q8IXM6	452

IntAct

2 interactions, top by confidence:

A	B	Type	Score
SUN3	GAS6	psi-mi:“MI:0914”(association)	0.350

BioGRID (7): SUN3 (Synthetic Lethality), PCYOX1L (Affinity Capture-MS), LPHN3 (Affinity Capture-MS), LAPTM4A (Affinity Capture-MS), TBC1D9 (Affinity Capture-MS), GAS6 (Affinity Capture-MS), XYLT2 (Affinity Capture-MS)

ESM2 similar proteins: A1L3I3, A2CI98, D3ZF92, O43278, O55034, O75509, O88393, O94901, P0C6P5, P35054, P59729, P98153, P98154, Q0II64, Q0VCT2, Q2KHT9, Q5BIR3, Q5HZE8, Q5PQS0, Q5RD34, Q5VUB5, Q61003, Q6AXX1, Q6DGF9, Q7TNI2, Q7TSI1, Q7Z2W4, Q80U38, Q8BJN4, Q8BJS4, Q8BZN4, Q8C2B3, Q8IUY3, Q8TAQ9, Q8TC36, Q8WUI4, Q8WYL5, Q91ZV2, Q91ZV3, Q95LV7

Diamond homologs: A0A0B4KEE4, O55034, O94901, Q09825, Q0II64, Q20745, Q5SS91, Q8BJS4, Q8TAQ9, Q8TC36, Q95LV7, Q9D666, Q9DA32, Q9JJF2, Q9NPE6, Q9UH99, Q9SG79, Q558Z2, Q9FF75

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SUN3	“form complex”	“LINC complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1710 predictions. Top by Δscore:

Variant	Effect	Δscore
7:48007150:AG:A	donor_gain	1.0000
7:48007166:T:TA	donor_gain	1.0000
7:48009033:A:AC	donor_gain	1.0000
7:48009034:C:CT	donor_gain	1.0000
7:48017250:A:C	donor_gain	1.0000
7:48017280:TGA:T	donor_gain	1.0000
7:48025876:CCTA:C	donor_gain	1.0000
7:48025937:CC:C	acceptor_gain	1.0000
7:48025938:CC:C	acceptor_gain	1.0000
7:48025939:C:CC	acceptor_gain	1.0000
7:47994313:A:AC	donor_gain	0.9900
7:47994314:C:CC	donor_gain	0.9900
7:47994328:T:TA	donor_gain	0.9900
7:47994351:T:TA	donor_gain	0.9900
7:47994478:TCCGG:T	acceptor_gain	0.9900
7:47994479:CCGG:C	acceptor_gain	0.9900
7:47994479:CCGGC:C	acceptor_gain	0.9900
7:47994480:CGGC:C	acceptor_gain	0.9900
7:47994483:C:CC	acceptor_gain	0.9900
7:47996025:CTTTA:C	donor_loss	0.9900
7:47996026:TTTAC:T	donor_loss	0.9900
7:47996027:TTA:T	donor_loss	0.9900
7:47996028:T:TG	donor_loss	0.9900
7:47996029:AC:A	donor_loss	0.9900
7:47996030:CCTG:C	donor_loss	0.9900
7:47996031:C:G	donor_loss	0.9900
7:47996143:GCTCC:G	acceptor_loss	0.9900
7:47996146:CCT:C	acceptor_loss	0.9900
7:47996148:T:C	acceptor_loss	0.9900
7:48009075:CCTG:C	acceptor_loss	0.9900

AlphaMissense

2356 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:47994391:A:T	V262D	0.993
7:47987367:C:G	R346P	0.991
7:47994456:C:A	W240C	0.991
7:47994456:C:G	W240C	0.991
7:47994319:A:T	V286D	0.990
7:47994395:C:G	A261P	0.990
7:47987358:A:T	V349D	0.989
7:47988797:A:C	F315L	0.989
7:47988797:A:T	F315L	0.989
7:47988799:A:G	F315L	0.989
7:47994458:A:G	W240R	0.987
7:47994458:A:T	W240R	0.987
7:47987415:A:G	L330P	0.981
7:47988833:A:C	F303L	0.981
7:47988833:A:T	F303L	0.981
7:47988835:A:G	F303L	0.981
7:48005983:G:T	A188D	0.980
7:47994334:G:T	P281H	0.979
7:48005980:A:G	L189P	0.979
7:47994324:A:C	F284L	0.978
7:47994324:A:T	F284L	0.978
7:47994326:A:G	F284L	0.978
7:47994325:A:G	F284S	0.976
7:47987364:A:G	F347S	0.975
7:47987360:C:A	R348S	0.973
7:47987360:C:G	R348S	0.973
7:47987399:G:C	N335K	0.973
7:47987399:G:T	N335K	0.973
7:47994339:A:C	S279R	0.973
7:47994339:A:T	S279R	0.973

dbSNP variants (sampled 300 via entrez): RS1000014556 (7:48024566 G>A), RS1000037577 (7:48009838 G>A), RS1000052287 (7:48009153 GAAAT>G), RS1000061909 (7:48033625 A>G), RS1000140707 (7:47993172 A>T), RS1000187558 (7:48035931 A>C), RS1000257208 (7:47992762 T>C), RS1000422940 (7:48021599 A>G), RS1000450328 (7:48028251 G>T), RS1000455494 (7:48029319 T>C,G), RS1000456298 (7:47991744 G>A,T), RS1000465476 (7:47987199 G>A), RS1000496841 (7:47998020 A>G), RS1000600868 (7:48004791 A>AGAAAT), RS1000651868 (7:48004472 C>G,T)

Disease associations

OMIM: gene MIM:618984 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, increases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
propionaldehyde	increases expression	1
bisphenol A	increases methylation	1
3,4-dichloroaniline	increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
coumarin	decreases phosphorylation	1
CGP 52608	affects binding, increases reaction	1
NSC 689534	affects binding, increases expression	1
(+)-JQ1 compound	decreases expression	1
Temozolomide	decreases expression	1
Cadmium	decreases expression, increases abundance	1
Copper	increases expression, affects binding	1
Diuron	increases expression	1
Formaldehyde	increases expression	1
Mustard Gas	increases expression	1
Silicon Dioxide	increases expression	1

Clinical trials (associated diseases)

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