SUN1

Summary

SUN1 (Sad1 and UNC84 domain containing 1, HGNC:18587) is a protein-coding gene on chromosome 7p22.3, encoding SUN domain-containing protein 1 (O94901). As a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex involved in the connection between the nuclear lamina and the cytoskeleton.

This gene is a member of the unc-84 homolog family and encodes a nuclear envelope protein with an Unc84 (SUN) domain. The protein is involved in nuclear anchorage and migration. Alternatively spliced transcript variants have been described.

Source: NCBI Gene 23353 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 693 total
• MANE Select transcript: NM_001130965

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18587
Approved symbol	SUN1
Name	Sad1 and UNC84 domain containing 1
Location	7p22.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0810, FLJ12407
Ensembl gene	ENSG00000164828
Ensembl biotype	protein_coding
OMIM	607723
Entrez	23353

Gene structure

Transcript identifiers

Ensembl transcripts: 201 — 183 protein_coding, 14 retained_intron, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000340926, ENST00000389574, ENST00000401592, ENST00000403868, ENST00000405266, ENST00000413171, ENST00000419312, ENST00000421580, ENST00000424128, ENST00000425407, ENST00000427969, ENST00000429178, ENST00000433212, ENST00000435699, ENST00000439679, ENST00000440380, ENST00000450538, ENST00000450881, ENST00000452783, ENST00000457378, ENST00000457598, ENST00000457861, ENST00000459810, ENST00000463848, ENST00000464442, ENST00000467483, ENST00000469755, ENST00000471349, ENST00000475971, ENST00000477950, ENST00000480475, ENST00000483996, ENST00000488628, ENST00000493681, ENST00000497943, ENST00000881147, ENST00000881148, ENST00000881149, ENST00000881150, ENST00000881151, ENST00000881152, ENST00000881153, ENST00000881154, ENST00000881155, ENST00000881156, ENST00000881157, ENST00000881158, ENST00000881159, ENST00000881160, ENST00000881161, ENST00000881162, ENST00000881163, ENST00000881164, ENST00000881165, ENST00000881166, ENST00000881167, ENST00000881168, ENST00000881169, ENST00000881170, ENST00000881171, ENST00000881172, ENST00000881173, ENST00000881174, ENST00000881175, ENST00000881176, ENST00000881177, ENST00000881178, ENST00000881179, ENST00000881180, ENST00000881181, ENST00000916963, ENST00000916964, ENST00000916965, ENST00000916966, ENST00000916967, ENST00000916968, ENST00000916969, ENST00000916970, ENST00000916971, ENST00000916972, ENST00000916973, ENST00000916974, ENST00000916975, ENST00000916976, ENST00000916977, ENST00000916978, ENST00000916979, ENST00000916980, ENST00000916981, ENST00000916982, ENST00000916983, ENST00000916984, ENST00000916985, ENST00000916986, ENST00000916987, ENST00000963073, ENST00000963074, ENST00000963075, ENST00000963076, ENST00000963077, ENST00000963078, ENST00000963079, ENST00000963080, ENST00000963081, ENST00000963082, ENST00000963083, ENST00000963084, ENST00000963085, ENST00000963086, ENST00000963087, ENST00000963088, ENST00000963089, ENST00000963090, ENST00000963091, ENST00000963093, ENST00000963094, ENST00000963096, ENST00000963098, ENST00000963099, ENST00000963100, ENST00000963101, ENST00000963102, ENST00000963103, ENST00000963104, ENST00000963105, ENST00000963106, ENST00000963107, ENST00000963108, ENST00000963109, ENST00000963110, ENST00000963111, ENST00000963112, ENST00000963113, ENST00000963114, ENST00000963115, ENST00000963116, ENST00000963117, ENST00000963118, ENST00000963119, ENST00000963120, ENST00000963121, ENST00000963122, ENST00000963123, ENST00000963124, ENST00000963125, ENST00000963126, ENST00000963127, ENST00000963128, ENST00000963129, ENST00000963130, ENST00000963131, ENST00000963132, ENST00000963133, ENST00000963134, ENST00000963135, ENST00000963136, ENST00000963137, ENST00000963138, ENST00000963139, ENST00000963140, ENST00000963141, ENST00000963142, ENST00000963143, ENST00000963144, ENST00000963145, ENST00000963146, ENST00000963147, ENST00000963148, ENST00000963149, ENST00000963150, ENST00000963151, ENST00000963152, ENST00000963153, ENST00000963154, ENST00000963155, ENST00000963156, ENST00000963157, ENST00000963158, ENST00000963159, ENST00000963160, ENST00000963161, ENST00000963162, ENST00000963163, ENST00000963164, ENST00000963165, ENST00000963166, ENST00000963167, ENST00000963168, ENST00000963169, ENST00000963170, ENST00000963171, ENST00000963172, ENST00000963173, ENST00000963174, ENST00000963175, ENST00000963176, ENST00000963177, ENST00000963178, ENST00000963179, ENST00000963180, ENST00000963181

RefSeq mRNA: 71 — MANE Select: NM_001130965 NM_001130965, NM_001171944, NM_001171945, NM_001171946, NM_001367633, NM_001367634, NM_001367635, NM_001367636, NM_001367638, NM_001367639, NM_001367640, NM_001367641, NM_001367642, NM_001367643, NM_001367644, NM_001367645, NM_001367646, NM_001367647, NM_001367648, NM_001367649, NM_001367651, NM_001367653, NM_001367655, NM_001367658, NM_001367660, NM_001367662, NM_001367664, NM_001367665, NM_001367666, NM_001367667, NM_001367668, NM_001367669, NM_001367670, NM_001367671, NM_001367672, NM_001367673, NM_001367674, NM_001367675, NM_001367676, NM_001367677, NM_001367678, NM_001367679, NM_001367680, NM_001367681, NM_001367682, NM_001367683, NM_001367684, NM_001367685, NM_001367686, NM_001367687, NM_001367688, NM_001367689, NM_001367690, NM_001367691, NM_001367692, NM_001367693, NM_001367694, NM_001367695, NM_001367696, NM_001367697, NM_001367698, NM_001367699, NM_001367700, NM_001367701, NM_001367702, NM_001367703, NM_001367704, NM_001367705, NM_001367706, NM_001367708, NM_025154

CCDS: CCDS43533, CCDS47525, CCDS55078, CCDS55079, CCDS55080, CCDS94043

Canonical transcript exons

ENST00000401592 — 19 exons

Exon	Start	End
ENSE00001087820	852810	852952
ENSE00003488547	854920	855006
ENSE00003524433	853409	853618
ENSE00003540778	851950	852043
ENSE00003554707	851384	851482
ENSE00003569233	843206	843232
ENSE00003569680	841946	842130
ENSE00003575416	872470	872562
ENSE00003596939	856358	856401
ENSE00003617407	869349	869516
ENSE00003645360	843341	843520
ENSE00003661366	857828	857957
ENSE00003669016	860128	860382
ENSE00003671366	865952	866067
ENSE00003684435	852609	852667
ENSE00003684688	861380	861464
ENSE00003788014	838798	838986
ENSE00003846297	873215	874934
ENSE00003846750	832476	832601

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.41.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.6573 / max 235.8016, expressed in 1809 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
76873	31.2118	1809
76876	0.2638	102
76875	0.1538	67
76874	0.0278	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.41	gold quality
oocyte	CL:0000023	99.38	gold quality
mucosa of stomach	UBERON:0001199	99.09	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.91	gold quality
right uterine tube	UBERON:0001302	98.79	gold quality
body of uterus	UBERON:0009853	98.64	gold quality
left ovary	UBERON:0002119	98.62	gold quality
bronchial epithelial cell	CL:0002328	98.61	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.58	gold quality
cerebellar hemisphere	UBERON:0002245	98.51	gold quality
endocervix	UBERON:0000458	98.45	gold quality
right ovary	UBERON:0002118	98.39	gold quality
skin of abdomen	UBERON:0001416	98.38	gold quality
skin of leg	UBERON:0001511	98.38	gold quality
cerebellar cortex	UBERON:0002129	98.33	gold quality
skin of hip	UBERON:0001554	98.29	gold quality
tibial nerve	UBERON:0001323	98.24	gold quality
ectocervix	UBERON:0012249	98.18	gold quality
epithelium of bronchus	UBERON:0002031	98.16	gold quality
cerebellum	UBERON:0002037	98.12	gold quality
bronchus	UBERON:0002185	98.11	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.11	gold quality
popliteal artery	UBERON:0002250	98.08	gold quality
tibial artery	UBERON:0007610	98.08	gold quality
zone of skin	UBERON:0000014	98.06	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.00	gold quality
lower esophagus	UBERON:0013473	97.99	gold quality
ovary	UBERON:0000992	97.96	gold quality
upper leg skin	UBERON:0004262	97.94	gold quality
pituitary gland	UBERON:0000007	97.90	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-CURD-97	no	431.09
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP63

miRNA regulators (miRDB)

61 targeting SUN1, 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-1252-5P	100.00	69.80	2774
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-379-3P	99.69	69.60	1524
HSA-MIR-411-3P	99.69	69.63	1524
HSA-MIR-4729	99.69	72.18	4233

Literature-anchored findings (GeneRIF, showing 38)

• Describes cloning and function of C. elegans unc-84 and cloning of human orthologs. (PMID:10375507)
• KIAA0810 is a novel 100-kDa transmembrane protein with similarity to Caenorhabditis elegans Unc-84A and resides in the inner nuclear membrane. It is likely to interact with the nuclear lamina. (PMID:11593002)
• Isolation of a cDNA encoding a mouse homolog of the human SUN1 (UNC84A) gene. (PMID:12036294)
• The Sun1 itself does not require functional A-type lamins for its localisation at the inner nuclear membrane in mammalian cells. (PMID:16079285)
• localization and anchoring of UNC84A is not dependent on the lamin proteins, in contrast to what had been observed for C. elegans UNC-84 (PMID:16445915)
• SUN1 and SUN2 may form a physical interaction between the nuclear envelope and the centrosome (PMID:17132086)
• chromosome de-condensation needs the function of an inner nuclear membrane (INM) protein hsSUN1 and a membrane-associated histone acetyltransferase (HAT), hALP. (PMID:17631499)
• Results suggest that Sun1 represents an important determinant of nuclear pore complex distribution across the nuclear surface. (PMID:17724119)
• perturbations in lamin A-SUN1 and SUN2 protein interactions may underlie the opposing effects of EDMD and HGPS mutations on nuclear and cellular mechanics (PMID:19933576)
• Nesprins, but not sun proteins, switch isoforms at the nuclear envelope during muscle development (PMID:20108321)
• These results demonstrate that the interplay between SUN1 and farnesylated prelamin A contributes to nuclear positioning in human myofibers and may be implicated in pathogenetic mechanisms. (PMID:21311568)
• POM121 and Sun1 interact transiently to promote early steps of interphase nuclear pore complexes assembly (PMID:21727197)
• Reduction of SUN1 overaccumulation in LMNA mutant fibroblasts and in cells derived from HGPS patients corrected nuclear defects and cellular senescence. (PMID:22541428)
• Results highlight the interactions at the nuclear envelope where mutations in the EMD and TMPO gene in combination with mutations in SUN1 have an impact on several components of the network. (PMID:24375709)
• Farnesylation of progerin enhances its interaction with SUN1 and reduces SUN1 mobility. (PMID:24522183)
• Codepletion of SUN1/2 slows cell proliferation and results in an accumulation of morphologically defective and disoriented mitotic spindles. (PMID:24662567)
• The Caenorhabditis elegans lamin, LMN-1, is required for nuclear migration and interacts with the nucleoplasmic domain of the SUN protein UNC-84. (PMID:25057012)
• An important role for SUN1 and SUN2 in muscle disease pathogenesis. (PMID:25210889)
• these data support a model whereby mitotic phosphorylation of SUN1 disrupts interactions with nucleoplasmic binding partners, promoting disassembly of the nuclear lamina and, potentially, its chromatin interactions (PMID:25482198)
• Nuclear envelope associated endosome-mediated transfer depends on the nuclear envelope proteins SUN1 and SUN2, as well as the Sec61 translocon complex. (PMID:26356418)
• SUN1 plays a role in hnRNP-involved mRNA export. (PMID:26476453)
• wndchrm revealed a consistent negative correlation between SUN1 expression and the size of nucleoli in human breast cancer tissues. (PMID:26962703)
• SUN1/SUN2 may function redundantly in early HIV-1 infection steps and therefore influence HIV-1 replication and pathogenesis. (PMID:28747499)
• Results provide evidence that SUN1 is involved in mRNA export and this function is regulated by phosphorylation of serine 113 in the N-terminal domain. (PMID:28831067)
• Thus, AID is a conserved functional domain in SUN proteins and this work provides the structural evidence to support the conversation of the AID-mediated autoinhibition of SUN proteins. (PMID:29408528)
• Mechanisms of SUN1 Oligomerization in the Nuclear Envelope (PMID:29539404)
• Low SUN1 expression is associated with HIV infections. (PMID:29643244)
• While Sun1 and Sun2 in HeLa cells are each able to bind KASH-domains, Sun1 is more efficiently incorporated into LINC complexes under normal growth conditions. Furthermore, the balance of Sun1 and Sun2 incorporated into LINC complexes is cell type-specific and is correlated with SRF/Mkl1-dependent gene expression. (PMID:29813079)
• Progerin overexpression increased levels of SUN1, which couples the nucleus to microtubules through nesprin-2G and dynein, and microtubule association with the nucleus. Reducing microtubule-nuclear connections through SUN1 depletion or dynein inhibition rescued the polarity defects. (PMID:30808750)
• SUN1/2 Are Essential for RhoA/ROCK-Regulated Actomyosin Activity in Isolated Vascular Smooth Muscle Cells. (PMID:31935926)
• The SUN1 splicing variants SUN1_888 and SUN1_916 differentially regulate nucleolar structure. (PMID:32931086)
• The SUN2-nesprin-2 LINC complex and KIF20A function in the Golgi dispersal. (PMID:33686165)
• The SUN1-SPDYA interaction plays an essential role in meiosis prophase I. (PMID:34039995)
• Nuclear restriction of HIV-1 infection by SUN1. (PMID:34580332)
• Homozygous missense mutation in CCDC155 disrupts the transmembrane distribution of CCDC155 and SUN1, resulting in non-obstructive azoospermia and premature ovarian insufficiency in humans. (PMID:35587281)
• Loss of SUN1 function in spermatocytes disrupts the attachment of telomeres to the nuclear envelope and contributes to non-obstructive azoospermia in humans. (PMID:36933034)
• SUN1 facilitates CHMP7 nuclear influx and injury cascades in sporadic amyotrophic lateral sclerosis. (PMID:37639327)
• SUN1 inhibits osteogenesis and promotes adipogenesis of human adipose-derived stem cells by regulating alpha-tubulin and CD36 expression. (PMID:39383106)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	sun1b	ENSDARG00000055350
danio_rerio	sun1a	ENSDARG00000077178
mus_musculus	Sun1	ENSMUSG00000036817
rattus_norvegicus	Sun1	ENSRNOG00000001299

Paralogs (4): SPAG4 (ENSG00000061656), SUN2 (ENSG00000100242), SUN3 (ENSG00000164744), SUN5 (ENSG00000167098)

Protein

Protein identifiers

SUN domain-containing protein 1 — O94901 (reviewed: O94901)

Alternative names: Protein unc-84 homolog A, Sad1/unc-84 protein-like 1

All UniProt accessions (14): A0A146IHP0, A0A8I5G938, C9JJU6, C9JK55, C9JR15, C9JS54, C9K051, E9PHI4, O94901, H0Y6N5, H0Y742, H7C019, H7C2K3, H7C3X3

UniProt curated annotations — full annotation on UniProt →

Function. As a 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. Required for interkinetic nuclear migration (INM) and essential for nucleokinesis and centrosome-nucleus coupling during radial neuronal migration in the cerebral cortex and during glial migration. Involved in telomere attachment to nuclear envelope in the prophase of meiosis implicating a SUN1/2:KASH5 LINC complex in which SUN1 and SUN2 seem to act at least partial redundantly. Required for gametogenesis and involved in selective gene expression of coding and non-coding RNAs needed for gametogenesis. Helps to define the distribution of nuclear pore complexes (NPCs). Required for efficient localization of SYNE4 in the nuclear envelope. May be involved in nuclear remodeling during sperm head formation in spermatogenesis. May play a role in DNA repair by suppressing non-homologous end joining repair to facilitate the repair of DNA cross-links.

Subunit / interactions. Core component of the LINC complex which is composed of inner nuclear membrane SUN domain-containing proteins coupled to outer nuclear membrane KASH domain-containing nesprins. SUN and KASH domain-containing proteins seem to bind each other promiscuously; however, differentially expression of LINC complex constituents is giving rise to specific assemblies. At least SUN1/2-containing core LINC complexes are proposed to be hexameric composed of three protomers of each KASH and SUN domain-containing protein. Interacts with KASH5 (via the last 22 amino acids); this interaction mediates KASH5 telomere localization by forming a SUN1:KASH5 LINC complex. May interact with SYNE3. Interacts with SYNE2 and SYNE1; probably forming respective LINC complexes. Interacts with A-type lamin with a strong preference for unprocessed A-type lamin compared with the mature protein. Interaction with lamins B1 and C is hardly detectable. Interacts with NAT10. Interacts with EMD and TSNAX. Associates with the nuclear pore complex (NPC). Interacts with CCDC79/TERB1; promoting the accumulation of the LINC complex complexes at the telomere-nuclear envelope attachment sites. Interacts (via KASH domain) with TMEM258.

Subcellular location. Nucleus inner membrane.

Post-translational modifications. The disulfide bond with KASH domain-containing nesprins is required for stability of the respective LINC complexes under tensile forces.

Domain organisation. The coiled coil domains differentially mediate trimerization required for binding to nesprins and are proposed to dynamically regulate the oligomeric state by locking the SUN domain in an inactive confirmation. The coiled coil domains are proposed to be involved in load-bearing and force transmission from the cytoskeleton. The SUN domain may play a role in nuclear anchoring and/or migration.

Isoforms (8)

UniProt ID	Names	Canonical?
O94901-8	1	yes
O94901-2	2
O94901-3	3
O94901-4	4
O94901-5	5
O94901-6	6
O94901-7	7
O94901-9	8

RefSeq proteins (71): NP_001124437, NP_001165415, NP_001165416, NP_001165417, NP_001354562, NP_001354563, NP_001354564, NP_001354565, NP_001354567, NP_001354568, NP_001354569, NP_001354570, NP_001354571, NP_001354572, NP_001354573, NP_001354574, NP_001354575, NP_001354576, NP_001354577, NP_001354578, NP_001354580, NP_001354582, NP_001354584, NP_001354587, NP_001354589, NP_001354591, NP_001354593, NP_001354594, NP_001354595, NP_001354596, NP_001354597, NP_001354598, NP_001354599, NP_001354600, NP_001354601, NP_001354602, NP_001354603, NP_001354604, NP_001354605, NP_001354606, NP_001354607, NP_001354608, NP_001354609, NP_001354610, NP_001354611, NP_001354612, NP_001354613, NP_001354614, NP_001354615, NP_001354616, NP_001354617, NP_001354618, NP_001354619, NP_001354620, NP_001354621, NP_001354622, NP_001354623, NP_001354624, NP_001354625, NP_001354626, NP_001354627, NP_001354628, NP_001354629, NP_001354630, NP_001354631, NP_001354632, NP_001354633, NP_001354634, NP_001354635, NP_001354637, NP_079430 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012919	SUN_dom	Domain
IPR032680	SUN1_N	Domain
IPR040994	Sun_CC2	Domain
IPR045119	SUN1-5	Family

Pfam: PF07738, PF09387, PF18580

UniProt features (58 total): strand 13, splice variant 11, sequence conflict 8, modified residue 5, helix 5, region of interest 4, sequence variant 3, topological domain 2, chain 1, disulfide bond 1, cross-link 1, transmembrane region 1, turn 1, domain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
6R2I	X-RAY DIFFRACTION	1.54
8B46	X-RAY DIFFRACTION	1.67
6R15	X-RAY DIFFRACTION	1.82
8B5X	X-RAY DIFFRACTION	1.98
8AU0	X-RAY DIFFRACTION	2.07
7Z8Y	X-RAY DIFFRACTION	2.29
6R16	X-RAY DIFFRACTION	2.75
7E34	X-RAY DIFFRACTION	3.19

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O94901-F1	60.99	0.18

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 (6): 138, 344, 195, 333, 48, 100

Disulfide bonds (1): 630

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-1221632	Meiotic synapsis
R-HSA-1474165	Reproduction
R-HSA-1500620	Meiosis
R-HSA-1640170	Cell Cycle

MSigDB gene sets: 247 (showing top): GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, GOBP_CHROMOSOME_ORGANIZATION, REACTOME_MEIOTIC_SYNAPSIS, GOBP_CHROMOSOME_LOCALIZATION, DARWICHE_SKIN_TUMOR_PROMOTER_UP, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_UP, GOBP_NEUROGENESIS, DARWICHE_SQUAMOUS_CELL_CARCINOMA_UP, GOBP_MALE_GAMETE_GENERATION, GOBP_ORGANELLE_TRANSPORT_ALONG_MICROTUBULE, GOBP_FOREBRAIN_DEVELOPMENT, chr7p22, GOBP_FOREBRAIN_CELL_MIGRATION, GOBP_ORGANELLE_FISSION

GO Biological Process (10): ossification (GO:0001503), homologous chromosome pairing at meiosis (GO:0007129), spermatogenesis (GO:0007283), response to mechanical stimulus (GO:0009612), nucleokinesis involved in cell motility in cerebral cortex radial glia guided migration (GO:0021817), centrosome localization (GO:0051642), meiotic attachment of telomere to nuclear envelope (GO:0070197), nuclear matrix anchoring at nuclear membrane (GO:0090292), cell differentiation (GO:0030154), meiotic cell cycle (GO:0051321)

GO Molecular Function (5): lamin binding (GO:0005521), identical protein binding (GO:0042802), protein-membrane adaptor activity (GO:0043495), cytoskeleton-nuclear membrane anchor activity (GO:0140444), protein binding (GO:0005515)

GO Cellular Component (8): chromosome, telomeric region (GO:0000781), nuclear envelope (GO:0005635), nuclear inner membrane (GO:0005637), cytoplasm (GO:0005737), nuclear membrane (GO:0031965), meiotic nuclear membrane microtubule tethering complex (GO:0034993), nucleus (GO:0005634), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Meiosis	1
Reproduction	1
Cell Cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	2
nucleus	2
cellular anatomical structure	2
multicellular organismal process	1
homologous chromosome segregation	1
chromosome organization involved in meiotic cell cycle	1
developmental process involved in reproduction	1
male gamete generation	1
response to external stimulus	1
response to abiotic stimulus	1
modulation of microtubule cytoskeleton involved in cerebral cortex radial glia guided migration	1
nuclear migration along microtubule	1
microtubule organizing center localization	1
meiotic telomere tethering at nuclear periphery	1
chromosome attachment to the nuclear envelope	1
meiotic cell cycle process	1
nuclear matrix organization	1
maintenance of protein location in nucleus	1
cellular developmental process	1
cell cycle	1
sexual reproduction	1
reproductive process	1
meiotic nuclear division	1
protein-macromolecule adaptor activity	1
protein-membrane adaptor activity	1
binding	1
chromosomal region	1
endomembrane system	1
organelle envelope	1
organelle inner membrane	1
nuclear membrane	1
intracellular anatomical structure	1
nuclear envelope	1
organelle membrane	1
microtubule organizing center attachment site	1
nuclear membrane microtubule tethering complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1502 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SUN1	SYNE2	Q8WXH0	999
SUN1	SYNE1	Q8NF91	999
SUN1	EMD	P50402	997
SUN1	KASH5	Q8N6L0	995
SUN1	LMNA	P02545	978
SUN1	TERB1	Q8NA31	968
SUN1	SUN2	Q9UH99	966
SUN1	TMEM201	Q5SNT2	950
SUN1	NUP153	P49790	919
SUN1	LMNB1	P20700	894
SUN1	SYNE4	Q8N205	855
SUN1	LMNB2	Q03252	842
SUN1	SYNE3	Q6ZMZ3	838
SUN1	TERB2	Q8NHR7	826
SUN1	H0YEC1	H0YEC1	815

IntAct

125 interactions, top by confidence:

A	B	Type	Score
FBXO28	TRAF5	psi-mi:“MI:0914”(association)	0.740
SUN1	SYNE1	psi-mi:“MI:0407”(direct interaction)	0.710
SYNE1	SUN1	psi-mi:“MI:0914”(association)	0.710
SUN1	SYNE4	psi-mi:“MI:0407”(direct interaction)	0.650
STX12	SNAP23	psi-mi:“MI:0914”(association)	0.640
SUN1	KASH5	psi-mi:“MI:0407”(direct interaction)	0.620
SUN1	IRAG2	psi-mi:“MI:0407”(direct interaction)	0.620
IRAG2	SUN1	psi-mi:“MI:0407”(direct interaction)	0.620
SUN1	SUN1	psi-mi:“MI:0407”(direct interaction)	0.610
EFTUD2	SART1	psi-mi:“MI:0914”(association)	0.610

BioGRID (217): SUN1 (Affinity Capture-MS), ZNF507 (Affinity Capture-MS), TYW5 (Affinity Capture-MS), TRIP6 (Affinity Capture-MS), SUN1 (Affinity Capture-MS), SUN1 (Affinity Capture-MS), SUN1 (Affinity Capture-MS), SUN1 (Affinity Capture-MS), SUN1 (Affinity Capture-MS), SUN1 (Affinity Capture-MS), SUN1 (Proximity Label-MS), SUN1 (Proximity Label-MS), SUN1 (Affinity Capture-MS), SUN1 (Proximity Label-MS), SUN1 (Affinity Capture-MS)

ESM2 similar proteins: A0A8M9PDM1, A0A8M9QN10, A1L3I3, A2AWH2, A2CI97, A2CI98, A4IFM1, A4IHZ3, A7E2V4, A7E305, B1AL88, B6CKP4, E7F211, F8W3R9, O55034, O94901, P35054, P51864, P86275, P98153, P98154, Q0VCT2, Q3UHH1, Q498C7, Q4KM46, Q4TUC0, Q58T08, Q5EB20, Q5HZE8, Q5RD34, Q5VUB5, Q6UW32, Q6V9Y8, Q7TNI2, Q7Z5A8, Q80ZA7, Q86VZ4, Q8CB67, Q8CCS2, Q8N0W7

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

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
PLK1	“down-regulates activity”	SUN1	phosphorylation
CDK1	“down-regulates activity”	SUN1	phosphorylation
PKC	“down-regulates activity”	SUN1	phosphorylation
SUN1	“up-regulates activity”	NUP153	binding
SUN1	“up-regulates activity”	NXF1	binding
SUN1	“up-regulates activity”	TERB1	binding
SUN1	“up-regulates activity”	MAJIN	binding
SUN1	“up-regulates activity”	SPDYA	binding
TP63	“up-regulates quantity by expression”	SUN1	“transcriptional regulation”
SUN1	“form complex”	“LINC complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	333
Likely benign	238
Benign	77

Top pathogenic / likely-pathogenic (0)

SpliceAI

6070 predictions. Top by Δscore:

Variant	Effect	Δscore
7:816672:AGGT:A	donor_loss	1.0000
7:816673:GGTG:G	donor_loss	1.0000
7:816674:G:C	donor_loss	1.0000
7:832493:C:A	acceptor_gain	1.0000
7:832503:A:AG	acceptor_gain	1.0000
7:832503:AGTAT:A	acceptor_gain	1.0000
7:832504:G:GG	acceptor_gain	1.0000
7:832504:GTATG:G	acceptor_gain	1.0000
7:838796:A:AG	acceptor_gain	1.0000
7:838797:G:GT	acceptor_gain	1.0000
7:838797:GTTCC:G	acceptor_gain	1.0000
7:838983:CCAGG:C	donor_loss	1.0000
7:838985:AGGT:A	donor_loss	1.0000
7:841941:CTTA:C	acceptor_loss	1.0000
7:841944:A:AG	acceptor_gain	1.0000
7:841945:G:GG	acceptor_gain	1.0000
7:841945:GA:G	acceptor_gain	1.0000
7:841945:GAA:G	acceptor_gain	1.0000
7:841945:GAAC:G	acceptor_gain	1.0000
7:841945:GAACA:G	acceptor_gain	1.0000
7:842127:TGGG:T	donor_gain	1.0000
7:842128:GGG:G	donor_gain	1.0000
7:842128:GGGG:G	donor_gain	1.0000
7:842129:GG:G	donor_gain	1.0000
7:842129:GGG:G	donor_gain	1.0000
7:842130:GG:G	donor_gain	1.0000
7:842131:G:GG	donor_gain	1.0000
7:842132:T:G	donor_loss	1.0000
7:843448:G:GT	donor_gain	1.0000
7:843516:AAAAT:A	donor_gain	1.0000

AlphaMissense

5111 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000023864 (7:867836 A>G), RS1000039222 (7:840487 C>T), RS1000054903 (7:871715 CAG>C), RS1000125234 (7:837645 G>C), RS1000139778 (7:868027 C>T), RS1000176324 (7:872586 C>A,G,T), RS1000221813 (7:859083 G>A), RS1000253980 (7:842907 G>A), RS1000295227 (7:849806 G>C), RS1000297020 (7:872745 A>C), RS1000312973 (7:858896 T>C), RS1000362023 (7:817054 G>A,C), RS1000364022 (7:847237 C>T), RS1000492509 (7:863312 G>A), RS1000517194 (7:823696 T>A)

Disease associations

OMIM: gene MIM:607723 | disease phenotypes: MIM:310300

GenCC curated gene-disease

Mondo (1): Emery-Dreifuss muscular dystrophy (MONDO:0016830)

Orphanet (1): Emery-Dreifuss muscular dystrophy (Orphanet:261)

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST004070_14	Cerebrospinal P-tau181p levels	5.000000e-07
GCST004864_43	Perceived unattractiveness to mosquitoes	6.000000e-06
GCST006061_204	Atrial fibrillation	5.000000e-08
GCST90002404_277	Red cell distribution width	2.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004763	p-tau measurement
EFO:0008380	perceived unattractiveness to mosquitos measurement
EFO:0009188	Red cell distribution width

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D020389	Muscular Dystrophy, Emery-Dreifuss	C05.651.534.500.350; C10.668.491.175.500.350; C16.320.322.625; C16.320.577.350

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

43 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation	3
Acetaminophen	increases expression	2
Valproic Acid	affects expression, increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
bisphenol A	increases methylation, affects cotreatment	1
trichostatin A	affects expression	1
arsenite	decreases reaction, affects binding	1
sodium arsenite	decreases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
AM 251	decreases expression	1
K 7174	increases expression	1
bisphenol S	affects cotreatment, decreases methylation	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Fulvestrant	increases methylation, decreases methylation, affects cotreatment	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Air Pollutants	affects cotreatment, decreases expression, increases abundance	1
Benztropine	affects cotreatment, decreases expression	1
Cannabidiol	affects cotreatment, decreases expression	1
Copper	affects binding, increases expression	1
Cuprizone	affects cotreatment, decreases expression	1
Disulfiram	affects binding, increases expression	1
Doxorubicin	increases expression	1
Endosulfan	decreases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C7YP	HAP1 SUN1 (-) SUN2 (-)	Cancer cell line	Male
CVCL_C7YQ	HAP1 SUN1 (-) 1	Cancer cell line	Male
CVCL_E2L8	HAP1 SUN1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01403402	Not specified	RECRUITING	Congenital Muscle Disease Study of Patient and Family Reported Medical Information