SYNE1

Summary

SYNE1 (spectrin repeat containing nuclear envelope protein 1, HGNC:17089) is a protein-coding gene on chromosome 6q25.2, encoding Nesprin-1 (Q8NF91). Multi-isomeric modular protein which forms a linking network between organelles and the actin cytoskeleton to maintain the subcellular spatial organization.

This gene encodes a spectrin repeat containing protein expressed in skeletal and smooth muscle, and peripheral blood lymphocytes, that localizes to the nuclear membrane. Mutations in this gene have been associated with autosomal recessive spinocerebellar ataxia 8, also referred to as autosomal recessive cerebellar ataxia type 1 or recessive ataxia of Beauce. Alternatively spliced transcript variants encoding different isoforms have been described.

Source: NCBI Gene 23345 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal recessive ataxia, Beauce type (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 37
• Clinical variants (ClinVar): 6,757 total — 199 pathogenic, 148 likely-pathogenic
• Phenotypes (HPO): 139
• MANE Select transcript: NM_182961

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17089
Approved symbol	SYNE1
Name	spectrin repeat containing nuclear envelope protein 1
Location	6q25.2
Locus type	gene with protein product
Status	Approved
Aliases	SYNE-1B, KIAA0796, 8B, Nesprin-1, enaptin, MYNE1, CPG2, dJ45H2.2, SCAR8, ARCA1, Nesp1
Ensembl gene	ENSG00000131018
Ensembl biotype	protein_coding
OMIM	608441
Entrez	23345

Gene structure

Transcript identifiers

Ensembl transcripts: 51 — 25 protein_coding, 18 retained_intron, 5 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay

ENST00000347037, ENST00000354674, ENST00000367248, ENST00000367251, ENST00000367253, ENST00000367255, ENST00000367256, ENST00000367257, ENST00000409694, ENST00000413186, ENST00000423061, ENST00000448038, ENST00000454018, ENST00000460912, ENST00000461872, ENST00000466159, ENST00000468937, ENST00000469439, ENST00000471834, ENST00000472563, ENST00000474655, ENST00000476519, ENST00000478916, ENST00000481502, ENST00000488376, ENST00000489156, ENST00000490135, ENST00000490866, ENST00000495090, ENST00000498751, ENST00000535081, ENST00000535896, ENST00000536990, ENST00000537033, ENST00000537750, ENST00000539504, ENST00000540663, ENST00000545694, ENST00000610489, ENST00000671915, ENST00000672122, ENST00000672154, ENST00000672169, ENST00000673163, ENST00000673173, ENST00000673281, ENST00000673451, ENST00000682179, ENST00000682252, ENST00000684208, ENST00000684643

RefSeq mRNA: 4 — MANE Select: NM_182961 NM_001347701, NM_001347702, NM_033071, NM_182961

CCDS: CCDS5236, CCDS87458, CCDS94022

Canonical transcript exons

ENST00000367255 — 146 exons

Exon	Start	End
ENSE00001378953	152636638	152636805
ENSE00002209989	152369471	152369614
ENSE00002226110	152336841	152337017
ENSE00002246673	152498742	152498792
ENSE00002276489	152334008	152334273
ENSE00002286239	152368972	152369127
ENSE00002287320	152367218	152367382
ENSE00003461030	152283978	152284172
ENSE00003461879	152430112	152430210
ENSE00003461989	152455426	152455590
ENSE00003463621	152325958	152326102
ENSE00003465968	152447458	152447622
ENSE00003467740	152428205	152428392
ENSE00003470465	152136618	152136818
ENSE00003471089	152526080	152526175
ENSE00003472590	152358373	152358537
ENSE00003475424	152224494	152224664
ENSE00003476595	152151553	152151690
ENSE00003479217	152206168	152206362
ENSE00003479889	152350168	152350335
ENSE00003484388	152347059	152347235
ENSE00003485618	152236817	152236948
ENSE00003487461	152221426	152221559
ENSE00003489467	152323478	152323737
ENSE00003493240	152293960	152294127
ENSE00003498343	152381006	152381362
ENSE00003501658	152218257	152218403
ENSE00003506076	152449533	152449641
ENSE00003507024	152231391	152231567
ENSE00003508127	152510193	152510371
ENSE00003508452	152244537	152244656
ENSE00003511448	152441130	152441270
ENSE00003512051	152225721	152225876
ENSE00003512843	152465982	152466078
ENSE00003513393	152376776	152376912
ENSE00003513496	152511011	152511103
ENSE00003513535	152132122	152132214
ENSE00003515568	152176394	152176560
ENSE00003515798	152309835	152310017
ENSE00003517669	152325084	152325302
ENSE00003520290	152269155	152269286
ENSE00003528517	152430482	152430709
ENSE00003531641	152316849	152316986
ENSE00003534822	152310688	152310873
ENSE00003535941	152155910	152156097
ENSE00003537376	152219003	152219185
ENSE00003538877	152396775	152396980
ENSE00003539537	152329730	152331890
ENSE00003541140	152520459	152520542
ENSE00003541405	152395516	152395671
ENSE00003543523	152505201	152505397
ENSE00003544051	152130720	152130778
ENSE00003544193	152390280	152390452
ENSE00003545300	152232116	152232265
ENSE00003545857	152278089	152278280
ENSE00003549618	152404213	152404314
ENSE00003555106	152249161	152249262
ENSE00003555947	152213612	152213759
ENSE00003557142	152413352	152413531
ENSE00003560481	152344081	152344227
ENSE00003560832	152450625	152450833
ENSE00003563575	152373037	152373219
ENSE00003564557	152465258	152465460
ENSE00003564771	152254880	152255089
ENSE00003573270	152262032	152262188
ENSE00003574981	152256634	152256765
ENSE00003575066	152300641	152300781
ENSE00003575208	152444411	152444578
ENSE00003576593	152442075	152442245
ENSE00003577216	152154892	152155042
ENSE00003578451	152435941	152436101
ENSE00003578915	152453586	152453720
ENSE00003579071	152407014	152407196
ENSE00003579103	152310396	152310518
ENSE00003580914	152502633	152502742
ENSE00003581158	152326296	152326633
ENSE00003584162	152362170	152362323
ENSE00003584189	152484835	152484972
ENSE00003584197	152458757	152458930
ENSE00003586941	152425381	152425547
ENSE00003590484	152387072	152387381
ENSE00003592856	152242240	152242440
ENSE00003594822	152149477	152149668
ENSE00003595680	152220842	152221046
ENSE00003596449	152236107	152236303
ENSE00003597917	152339241	152339366
ENSE00003600162	152143623	152143765
ENSE00003601034	152455886	152456044
ENSE00003602237	152164163	152164325
ENSE00003604375	152628265	152628554
ENSE00003605200	152207972	152208206
ENSE00003605868	152409068	152409226
ENSE00003608454	152461597	152461740
ENSE00003609358	152471597	152471765
ENSE00003610922	152488396	152488503
ENSE00003611600	152463353	152463517
ENSE00003611847	152133276	152133488
ENSE00003612102	152281807	152281980
ENSE00003612786	152318863	152319015
ENSE00003613632	152318081	152318263
ENSE00003615303	152353589	152353744
ENSE00003616159	152399616	152399823
ENSE00003616478	152301869	152302063
ENSE00003616759	152293588	152293749
ENSE00003618260	152189252	152189407
ENSE00003620360	152398619	152398731
ENSE00003620702	152230547	152230702
ENSE00003627367	152419569	152419722
ENSE00003631167	152148045	152148378
ENSE00003631226	152409559	152409709
ENSE00003634323	152539960	152540021
ENSE00003635198	152211494	152211588
ENSE00003635238	152321238	152321390
ENSE00003635433	152141203	152141329
ENSE00003636355	152121687	152122676
ENSE00003636449	152359315	152359458
ENSE00003636890	152376381	152376558
ENSE00003637704	152352027	152352353
ENSE00003640551	152462738	152462890
ENSE00003640637	152354659	152354976
ENSE00003641415	152268056	152268165
ENSE00003641967	152472301	152472413
ENSE00003642560	152308489	152308632
ENSE00003642959	152214906	152215060
ENSE00003647188	152350618	152350770
ENSE00003653695	152135104	152135232
ENSE00003655736	152385674	152385838
ENSE00003655930	152451047	152451205
ENSE00003661515	152201824	152201949
ENSE00003665216	152239533	152239706
ENSE00003667521	152151959	152152141
ENSE00003667888	152483085	152483249
ENSE00003670268	152353263	152353433
ENSE00003677183	152433795	152433945
ENSE00003680055	152391277	152391568
ENSE00003682087	152180136	152180294
ENSE00003685430	152401138	152401341
ENSE00003685463	152427693	152427816
ENSE00003685575	152255591	152255746
ENSE00003687918	152139950	152140161
ENSE00003689437	152416387	152417015
ENSE00003691265	152234668	152234800
ENSE00003691662	152233781	152233963
ENSE00003693993	152364847	152365019
ENSE00003725419	152321721	152321886
ENSE00003841731	152637189	152637362

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 98.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.7027 / max 2915.4627, expressed in 1586 samples.

FANTOM5 promoters (56 alternative TSS)

Promoter ID	TPM avg	Samples expressed
76231	12.8355	1161
76220	4.1668	1032
76260	3.0198	313
76261	1.0188	174
76200	0.8938	103
76264	0.7894	235
76244	0.5525	94
76259	0.4957	147
76248	0.3352	19
76265	0.3245	143

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar hemisphere	UBERON:0002245	98.84	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.79	gold quality
calcaneal tendon	UBERON:0003701	98.73	gold quality
cerebellar cortex	UBERON:0002129	98.71	gold quality
cerebellum	UBERON:0002037	98.58	gold quality
nucleus accumbens	UBERON:0001882	97.43	gold quality
sural nerve	UBERON:0015488	97.38	gold quality
left ovary	UBERON:0002119	97.24	gold quality
right lung	UBERON:0002167	97.22	gold quality
middle temporal gyrus	UBERON:0002771	97.19	gold quality
caudate nucleus	UBERON:0001873	97.15	gold quality
right frontal lobe	UBERON:0002810	97.15	gold quality
ascending aorta	UBERON:0001496	96.96	gold quality
thoracic aorta	UBERON:0001515	96.96	gold quality
descending thoracic aorta	UBERON:0002345	96.87	gold quality
right uterine tube	UBERON:0001302	96.85	gold quality
pituitary gland	UBERON:0000007	96.69	gold quality
putamen	UBERON:0001874	96.69	gold quality
left lobe of thyroid gland	UBERON:0001120	96.65	gold quality
tendon	UBERON:0000043	96.56	gold quality
primary visual cortex	UBERON:0002436	96.56	gold quality
caput epididymis	UBERON:0004358	96.56	gold quality
right lobe of thyroid gland	UBERON:0001119	96.44	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.44	gold quality
right ovary	UBERON:0002118	96.43	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.40	gold quality
aorta	UBERON:0000947	96.37	gold quality
thyroid gland	UBERON:0002046	96.34	gold quality
adenohypophysis	UBERON:0002196	96.26	gold quality
pons	UBERON:0000988	96.25	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-GEOD-131882	yes	9046.53
E-CURD-119	yes	8176.79
E-MTAB-6819	yes	3605.98
E-GEOD-150728	yes	2699.44
E-GEOD-81383	yes	1128.86
E-GEOD-93593	yes	391.65
E-CURD-122	yes	46.46
E-GEOD-137537	yes	15.29
E-MTAB-6678	yes	11.57
E-MTAB-7606	no	1287.05
E-MTAB-8911	no	713.77
E-MTAB-7381	no	219.46
E-CURD-112	no	2.95
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

41 targeting SYNE1, 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-6740-5P	100.00	65.64	932
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-567	99.63	68.57	1219
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-548G-3P	99.48	68.67	2159
HSA-MIR-297	99.40	69.58	1418
HSA-MIR-302A-5P	99.39	68.21	1913
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-4473	98.89	69.10	652
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-4272	98.76	68.74	1810
HSA-MIR-6796-3P	98.68	65.49	689
HSA-MIR-5581-3P	98.55	70.31	1161

Literature-anchored findings (GeneRIF, showing 40)

• Vertebrate Nesprin-1 and nesprin-2 proteins are orthologous to Drosophila melanogaster muscle protein MSP-300 (PMID:12408964)
• The role of Syne-1 in cytokinesis involves an interaction with kinesin II. (PMID:14709720)
• Enaptin is an element of the nuclear membrane and the actin cytoskeleton. (PMID:15093733)
• The Nesprin-1 is essential for the interaction with a C-terminal region in SUN1 protein. (PMID:16079285)
• These findings indicate that GSRP-56 is a small Golgi-localized splice-isoform of the spectrin-repeat-containing Syne1 gene. (PMID:16875688)
• SYNE1 is the first identified gene responsible for a recessively inherited pure cerebellar ataxia. (PMID:17159980)
• The characterisation of the residues both in emerin and in nesprin-1alpha and -2beta which are involved in their interaction is reported. (PMID:17462627)
• This study identified a cluster of French-Canadian families with a new recessive ataxia of relatively pure cerebellar type caused by mutations in SYNE1. (PMID:17503513)
• Screening for DNA variations in the genes encoding nesprin-1 (SYNE1) and nesprin-2 (SYNE2) in 190 probands with Emery Dreifuss muscular dystrophy identified four heterozygous missense mutations. (PMID:17761684)
• Loss of Drop1 expression at early stages in carcinomas of the uterus, cervix, kidney, lung, thyroid and pancreas. (PMID:18709643)
• association with human nesprin-3 appeared to be stronger for torsinADeltaE than for torsinA. TorsinA also associated with the KASH domains of nesprin-1 and -2 (PMID:18827015)
• splice site mutation of SYNE-1 gene found in the family is responsible for arthrogryposis multiplex congenita. (PMID:19542096)
• analysis of nsprin-1 mutations in human and murine cardiomyopathy (PMID:19944109)
• a single nucleotide polymorphism downstream of ESR1, a gene called spectrin repeat containing, nuclear envelope 1, was associated with invasive ovarian cancer risk (PMID:20056644)
• Nesprins, but not sun proteins, switch isoforms at the nuclear envelope during muscle development (PMID:20108321)
• Nesprin-1 depletion increased the number of focal adhesions and substrate traction while decreasing the speed of cell migration (PMID:20655839)
• The findings of this study add to the evidence that association of SYNE1 mutation influences susceptibility to bipolar and unipolar mood disorders. (PMID:22565781)
• Study presents crystal structures of the human SUN2-KASH1/2 complex, i.e. SUN2 complexed with the C-terminal 29 residues of human Nesprin-1 or -2 (the core of the LINC complex). (PMID:22632968)
• These results indicate that nesprin-1 knockdown releases the nucleus from the tension of F-actin bound to the nucleus, thereby increasing allowance for deformation before stretching, and that F-actin bound to the nucleus through nesprin-1 causes sustainable force transmission to the nucleus. (PMID:22728879)
• Multiple novel nesprin-1 and nesprin-2 variants act as versatile tissue-specific intracellular scaffolds. (PMID:22768332)
• we report 4 novel homozygous SYNE1 mutations in 3 Japanese patients with cerebellar ataxia (PMID:23325900)
• Two novel truncating mutations were found among the French-Canadian participants, and 2 other novel mutations were found in a patient from France and a patient from Brazil. (PMID:23959263)
• FOXE1 and SYNE1 hypermethylation markers demonstrated significantly increased expression in neoplastic tissue. (PMID:24280874)
• role of CSMD1 and SYNE1 in the etiology of bipolar disorder (PMID:24387768)
• The significance of these shorter isoforms of nesprin, were evaluated. (PMID:24718612)
• a role for Nesprin-1 in the DNA damage response pathway (PMID:24781983)
• These data identify p50(Nesp1) as a multi-functional P-body component and microtubule scaffold necessary for RNA granule dynamics and provides evidence for P-body and stress granule micro-heterogeneity. (PMID:24862572)
• nesprin-1 and nesprin-2 both regulate nuclear and cytoplasmic architecture. (PMID:24931616)
• A report of a family with a SYNE1 gene mutation that seems to cause an “Emery-Dreifuss muscular dystrophy-like” phenotype. (PMID:25091525)
• ur results show that SNPs rs9371601 and rs3093664 in the SYNE1 and TNF genes respectively, are associated with menstrual migraine. (PMID:25315199)
• our data suggest that SYNE1 and FOXE1 are promising markers for colorectal cancer detection. (PMID:25538088)
• Drosophila melanogaster larval muscles, exhibiting both elastic features contributed by the stretching capacity of MSP300 (nesprin) and rigidity provided by a perinuclear network of microtubules stabilized by Shot (spectraplakin) and EB1. (PMID:26008743)
• SNP rs79575945 in ESR1 gene is associated with cancers of endometrioid subtype and resulted in the expression of SYNE1. (PMID:26330482)
• A full length transcript homologous to rat CPG2 exists within human SYNE1. A full length transcript homologous to rat CPG2 exists within human SYNE1. (PMID:26704904)
• Mechanostimulation mediates nuclear changes in oligodendrocyte progenitor cells via the SYNE1 complex. (PMID:26791211)
• findings revise the view that SYNE1 ataxia causes mainly a relatively pure cerebellar recessive ataxia and that it is largely limited to Quebec. Instead, complex phenotypes with a wide range of extra-cerebellar neurological and nonneurological dysfunctions are frequent, including in particular motor neuron and brainstem dysfunction. (PMID:27086870)
• This study demonstrate four novel truncating mutations in SYNE1 in pedigrees from British, Sri Lankan and Turkish origin in patient with cerebellar ataxia. (PMID:27178001)
• The results show that nesprin-1-alpha2 is dynamically controlled and may be involved in some process occurring during early myofibre formation, such as re-positioning of nuclei. (PMID:27350129)
• The frequency of CACNA1C rs10848683 in genetic high-risk individuals was double that in controls. For SYNE1 rs214950, higher frequencies were found in the genetic high-risk group than in controls. Polymorphisms in CACNA1C and SYNE1 could confer a greater risk of developing Schizophrenia and Bipolar Disorder in individuals who are already at high risk because of their family history. (PMID:27620326)
• Nonsense mutation in the ultimate exon of full-length SYNE1 causes congenital onset of muscular weakness with distal arthrogryposis. (PMID:27782104)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	syne1a	ENSDARG00000009499
mus_musculus	Syne1	ENSMUSG00000096054
rattus_norvegicus	Syne1	ENSRNOG00000018960

Paralogs (36): SYNE2 (ENSG00000054654), SPTB (ENSG00000070182), ACTN1 (ENSG00000072110), ACTN2 (ENSG00000077522), DSP (ENSG00000096696), DRP2 (ENSG00000102385), SPTBN1 (ENSG00000115306), MACF1 (ENSG00000127603), FLNC (ENSG00000128591), ACTN4 (ENSG00000130402), MICAL2 (ENSG00000133816), DTNA (ENSG00000134769), MICAL1 (ENSG00000135596), FLNB (ENSG00000136068), SPTBN5 (ENSG00000137877), DTNB (ENSG00000138101), GAS2L3 (ENSG00000139354), DST (ENSG00000151914), UTRN (ENSG00000152818), SPTBN4 (ENSG00000160460), SPTA1 (ENSG00000163554), CLMN (ENSG00000165959), PKHD1 (ENSG00000170927), SPTBN2 (ENSG00000173898), SYNE3 (ENSG00000176438), PLEC (ENSG00000178209), SMTNL2 (ENSG00000188176), FLNA (ENSG00000196924), SPTAN1 (ENSG00000197694), DMD (ENSG00000198947), PKHD1L1 (ENSG00000205038), DYTN (ENSG00000232125), MICAL3 (ENSG00000243156), ACTN3 (ENSG00000248746), EPPK1 (ENSG00000261150), GAS2L2 (ENSG00000270765)

Protein

Protein identifiers

Nesprin-1 — Q8NF91 (reviewed: Q8NF91)

Alternative names: Enaptin, KASH domain-containing protein 1, Myocyte nuclear envelope protein 1, Nuclear envelope spectrin repeat protein 1, Synaptic nuclear envelope protein 1

All UniProt accessions (26): Q8NF91, A0A0C4DG40, A0A0C4DH48, A0A5F9ZH00, A0A5F9ZH86, A0A5F9ZH87, A0A5F9ZHB2, A0A5F9ZHD7, A0A5F9ZHE1, A0A5F9ZHI3, A0A5F9ZHR3, A0A5F9ZI52, B7Z9Y6, F5GXQ8, F5GYQ7, F5GZ83, F5H422, F5H4Q0, F5H6R8, F8WAI0, H0Y325, H0Y326, H0YFT4, H0YGD3, I6XKI8, Q5JV20

UniProt curated annotations — full annotation on UniProt →

Function. Multi-isomeric modular protein which forms a linking network between organelles and the actin cytoskeleton to maintain the subcellular spatial organization. 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. May be involved in nucleus-centrosome attachment and nuclear migration in neural progenitors implicating LINC complex association with SUN1/2 and probably association with cytoplasmic dynein-dynactin motor complexes; SYNE1 and SYNE2 may act redundantly. Required for centrosome migration to the apical cell surface during early ciliogenesis. May be involved in nuclear remodeling during sperm head formation in spermatogenesis; a probable SUN3:SYNE1/KASH1 LINC complex may tether spermatid nuclei to posterior cytoskeletal structures such as the manchette.

Subunit / interactions. Core component of LINC complexes which are 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 can give 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. The SUN2:SYNE1/KASH1 LINC complex is a heterohexamer; the homotrimeric cloverleave-like conformation of the SUN domain is a prerequisite for LINC complex formation in which three separate SYNE1/KASH1 peptides bind at the interface of adjacent SUN domains. Self-associates. Interacts with SYNE3. Interacts with SPAG4/SUN4. May interact with MUSK. Interacts with F-actin via its N-terminal domain. Interacts with EMD and LMNA in vitro. Interacts (via KASH domain) with TMEM258.

Subcellular location. Nucleus outer membrane. Nucleus. Nucleus envelope. Cytoplasm. Cytoskeleton. Myofibril. Sarcomere Golgi apparatus.

Tissue specificity. Expressed in HeLa, A431, A172 and HaCaT cells (at protein level). Widely expressed. Highly expressed in skeletal and smooth muscles, heart, spleen, peripheral blood leukocytes, pancreas, cerebellum, stomach, kidney and placenta. Isoform GSRP-56 is predominantly expressed in heart and skeletal muscle (at protein level).

Post-translational modifications. The disulfid bond with SUN1 or SUN2 is required for stability of the respective LINC complex under tensile forces.

Disease relevance. Spinocerebellar ataxia, autosomal recessive, 8 (SCAR8) [MIM:610743] A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR8 is an autosomal recessive form. The disease is caused by variants affecting the gene represented in this entry. Emery-Dreifuss muscular dystrophy 4, autosomal dominant (EDMD4) [MIM:612998] A form of Emery-Dreifuss muscular dystrophy, a degenerative myopathy characterized by weakness and atrophy of muscle without involvement of the nervous system, early contractures of the elbows, Achilles tendons and spine, and cardiomyopathy associated with cardiac conduction defects. The disease is caused by variants affecting the gene represented in this entry. Arthrogryposis multiplex congenita 3, myogenic type (AMC3) [MIM:618484] A form of arthrogryposis multiplex congenita, a heterogeneous group of disorders characterized by multiple joint contractures resulting, in some cases, from reduced or absent fetal movements. AMC3 is an autosomal recessive form characterized by decreased fetal movements, muscular hypotonia, delayed motor development, loss of ambulation, variable skeletal defects, and persistent contractures of interphalangeal joints. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The KASH domain, which contains a transmembrane domain, mediates the nuclear envelope targeting and is involved in the binding to SUN1 and SUN2 through recognition of their SUN domains.

Miscellaneous. Lost in uterus, cervix, kidney, lung, thyroid and pancreas carcinomas, already at early tumor stages. Muscle-specific. Interacts with TRPV2.

Similarity. Belongs to the nesprin family.

Isoforms (12)

UniProt ID	Names	Canonical?
Q8NF91-1	1, Nesprin-1 Giant, Enaptin	yes
Q8NF91-2	2, Beta
Q8NF91-3	3, Alpha
Q8NF91-4	4
Q8NF91-5	5
Q8NF91-6	6
Q8NF91-7	7
Q8NF91-8	8, Beta 2
Q8NF91-9	9, Alpha 2
Q8NF91-10	10, drop1
Q8NF91-11	11, myne-1, 131kDa
Q8NF91-12	GSRP-56, 56kDa

RefSeq proteins (4): NP_001334630, NP_001334631, NP_149062, NP_892006* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001589	Actinin_actin-bd_CS	Conserved_site
IPR001715	CH_dom	Domain
IPR002017	Spectrin_repeat	Repeat
IPR012315	KASH	Domain
IPR018159	Spectrin/alpha-actinin	Repeat
IPR036872	CH_dom_sf	Homologous_superfamily
IPR047290	CH_SYNE1_rpt1	Domain
IPR047291	CH_SYNE1_rpt2	Domain
IPR056887	SYNE1/2_dom	Domain
IPR057057	Spectrin_SYNE1	Domain
IPR057932	Spectrin_SYNE1_3	Domain

Pfam: PF00307, PF00435, PF10541, PF25034, PF25035, PF25803

UniProt features (181 total): repeat 74, sequence variant 40, splice variant 22, sequence conflict 14, modified residue 9, region of interest 4, domain 3, compositionally biased region 3, topological domain 2, helix 2, strand 2, disulfide bond 2, chain 1, mutagenesis site 1, transmembrane region 1, coiled-coil region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6R15	X-RAY DIFFRACTION	1.82
4DXR	X-RAY DIFFRACTION	2.32
6XF2	X-RAY DIFFRACTION	7.11

Predicted structure (AlphaFold)

No AlphaFold model available for Q8NF91 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

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 (9): 732, 2270, 5657, 8223, 8274, 8277, 8280, 8305, 8360

Disulfide bonds (2): 8774, 8774

Mutagenesis-validated functional residues (1):

Position	Phenotype
8758–8763	abolishes the nuclear envelope targeting, induces a cytoplasmic localization.

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: 565 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, BENPORATH_ES_WITH_H3K27ME3, REACTOME_MEIOTIC_SYNAPSIS, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, RORA1_01, GCANCTGNY_MYOD_Q6, MODULE_45, KENNY_CTNNB1_TARGETS_UP, TATTATA_MIR374, GOBP_MALE_GAMETE_GENERATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, AGGCACT_MIR5153P, MODULE_66, chr6q25, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION

GO Biological Process (6): nucleus organization (GO:0006997), Golgi organization (GO:0007030), spermatogenesis (GO:0007283), muscle cell differentiation (GO:0042692), nuclear matrix anchoring at nuclear membrane (GO:0090292), cell differentiation (GO:0030154)

GO Molecular Function (9): RNA binding (GO:0003723), actin binding (GO:0003779), lamin binding (GO:0005521), enzyme binding (GO:0019899), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), actin filament binding (GO:0051015), cytoskeleton-nuclear membrane anchor activity (GO:0140444), protein binding (GO:0005515)

GO Cellular Component (14): P-body (GO:0000932), nucleus (GO:0005634), nuclear envelope (GO:0005635), nuclear outer membrane (GO:0005640), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytoskeleton (GO:0005856), membrane (GO:0016020), sarcomere (GO:0030017), nuclear membrane (GO:0031965), meiotic nuclear membrane microtubule tethering complex (GO:0034993), postsynaptic membrane (GO:0045211)

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
cellular anatomical structure	4
protein binding	3
organelle organization	2
intracellular membrane-bounded organelle	2
nucleus	2
endomembrane system	2
nuclear lumen	2
intracellular membraneless organelle	2
endomembrane system organization	1
developmental process involved in reproduction	1
male gamete generation	1
cell differentiation	1
muscle structure development	1
nuclear matrix organization	1
maintenance of protein location in nucleus	1
cellular developmental process	1
nucleic acid binding	1
cytoskeletal protein binding	1
identical protein binding	1
protein dimerization activity	1
actin binding	1
protein-containing complex binding	1
protein-membrane adaptor activity	1
binding	1
cytoplasmic ribonucleoprotein granule	1
organelle envelope	1
nuclear membrane	1
organelle outer membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
intracellular anatomical structure	1
cytoplasm	1
myofibril	1
nuclear envelope	1
organelle membrane	1
microtubule organizing center attachment site	1
nuclear membrane microtubule tethering complex	1
synaptic membrane	1
postsynapse	1

Protein interactions and networks

STRING

2658 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SYNE1	SUN1	O94901	999
SYNE1	SUN2	Q9UH99	999
SYNE1	EMD	P50402	995
SYNE1	LMNA	P02545	970
SYNE1	SYNE4	Q8N205	869
SYNE1	MUSK	O15146	819
SYNE1	SUN3	Q8TAQ9	813
SYNE1	PLEC	Q15149	810
SYNE1	LMNB1	P20700	785
SYNE1	FHOD1	Q9Y613	765
SYNE1	SPAG4	Q9NPE6	737
SYNE1	LEMD3	Q9Y2U8	709
SYNE1	SUN5	Q8TC36	686
SYNE1	TOR1A	O14656	678
SYNE1	TTN	Q8WZ42	678

IntAct

85 interactions, top by confidence:

A	B	Type	Score
SUN2	SYNE1	psi-mi:“MI:0407”(direct interaction)	0.810
SUN2	SYNE1	psi-mi:“MI:0915”(physical association)	0.810
SYNE1	SUN2	psi-mi:“MI:0407”(direct interaction)	0.810
SUN1	SYNE1	psi-mi:“MI:0407”(direct interaction)	0.710
SYNE1	SUN1	psi-mi:“MI:0914”(association)	0.710
IFT57	IFT56	psi-mi:“MI:0914”(association)	0.640
DISC1	SYNE1	psi-mi:“MI:0915”(physical association)	0.630
SYNE1	DISC1	psi-mi:“MI:0915”(physical association)	0.630
SYNE1	HMGN2	psi-mi:“MI:0915”(physical association)	0.400
SYNE1	AXDND1	psi-mi:“MI:0915”(physical association)	0.400
SYNE1	H1-5	psi-mi:“MI:0915”(physical association)	0.400
SYNE1	DDX23	psi-mi:“MI:0915”(physical association)	0.400
Nde1	RPA2	psi-mi:“MI:0915”(physical association)	0.400
SYNE1	BDKRB2	psi-mi:“MI:0915”(physical association)	0.370
SYNE1	PTCHD1	psi-mi:“MI:0915”(physical association)	0.370
SYNE1		psi-mi:“MI:0915”(physical association)	0.370
	SYNE1	psi-mi:“MI:0915”(physical association)	0.370
PPEF1	IRS4	psi-mi:“MI:0914”(association)	0.350
KSR1	DDX39A	psi-mi:“MI:0914”(association)	0.350
KSR1	FBLL1	psi-mi:“MI:0914”(association)	0.350
KSR1	FAM168B	psi-mi:“MI:0914”(association)	0.350
DND1	RPSA2	psi-mi:“MI:0914”(association)	0.350

BioGRID (143): SYNE1 (Affinity Capture-MS), SYNE1 (Affinity Capture-MS), SYNE1 (Affinity Capture-MS), SYNE1 (Affinity Capture-MS), SYNE1 (Affinity Capture-MS), SYNE1 (Affinity Capture-MS), SYNE1 (Co-fractionation), SYNE1 (Affinity Capture-MS), SYNE1 (Affinity Capture-MS), SYNE1 (Proximity Label-MS), SYNE1 (Proximity Label-MS), SYNE1 (Affinity Capture-MS), SYNE1 (Affinity Capture-MS), SYNE1 (Affinity Capture-MS), SYNE1 (Affinity Capture-MS)

ESM2 similar proteins: A0A8M2BID5, A0A8M9PQ61, A1Z7A6, D3ZHV2, E9Q557, F1LMV6, F1M0Z1, G3V7L1, O43150, O60229, O60437, O75962, O97592, O97902, P0CE94, P0CE95, P10911, P11530, P11531, P11532, P11533, P15924, P30427, P33175, P46939, Q03001, Q0KL02, Q15149, Q1AAU6, Q1LUA6, Q5GN48, Q6ZWR6, Q7SIG6, Q8CIS0, Q8NF91, Q8WXH0, Q91ZU6, Q92817, Q95RG8, Q9BXL7

Diamond homologs: A5D7D1, D3ZEN0, D3ZHA0, D3ZHV2, D3ZQL6, E1BBG2, F1MF74, F1RA39, F6QZ15, G3MWR8, G3V7L1, L7UZ85, M9MRD1, O13728, O15020, O43707, O75369, O76329, O88990, O94851, O97592, P05094, P05095, P07751, P11277, P11530, P11531, P11532, P11533, P12814, P13395, P13466, P15508, P16086, P16546, P18091, P20111, P21333, P30427, P35609

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SYNE1	“up-regulates activity”	MSH2/MSH6	binding
SYNE1	“form complex”	“LINC complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

6757 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	199
Likely pathogenic	148
Uncertain significance	3375
Likely benign	1807
Benign	448

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1013313	NM_182961.4(SYNE1):c.67+1G>T	Pathogenic
1027458	NM_182961.4(SYNE1):c.15049C>T (p.Gln5017Ter)	Pathogenic
1027459	NM_182961.4(SYNE1):c.7085dup (p.Asn2362fs)	Pathogenic
1027460	NM_182961.4(SYNE1):c.6724-1G>A	Pathogenic
1027482	NM_182961.4(SYNE1):c.4609C>T (p.Arg1537Ter)	Pathogenic
1027483	NM_182961.4(SYNE1):c.7911G>A (p.Trp2637Ter)	Pathogenic
1027484	NM_182961.4(SYNE1):c.3130C>T (p.Arg1044Ter)	Pathogenic
1027531	NM_182961.4(SYNE1):c.706C>T (p.Arg236Ter)	Pathogenic
1065639	NM_182961.4(SYNE1):c.17872_17875del (p.Leu5958fs)	Pathogenic
1068459	NM_182961.4(SYNE1):c.21781C>T (p.Arg7261Ter)	Pathogenic
1069554	NM_182961.4(SYNE1):c.20179del (p.Asp6727fs)	Pathogenic
1071645	NM_182961.4(SYNE1):c.5895del (p.Leu1966fs)	Pathogenic
1072998	NM_182961.4(SYNE1):c.16111C>T (p.Arg5371Ter)	Pathogenic
1073796	NM_182961.4(SYNE1):c.5525dup (p.Gln1843fs)	Pathogenic
1075274	NM_182961.4(SYNE1):c.2992C>T (p.Gln998Ter)	Pathogenic
1174498	NM_182961.4(SYNE1):c.16228C>T (p.Arg5410Ter)	Pathogenic
1184549	NM_182961.4(SYNE1):c.67+1G>A	Pathogenic
1184951	NM_182961.4(SYNE1):c.24814C>T (p.Arg8272Ter)	Pathogenic
1184952	NM_182961.4(SYNE1):c.14813T>A (p.Leu4938Ter)	Pathogenic
1184962	NM_182961.4(SYNE1):c.11205del (p.Ile3735fs)	Pathogenic
1256356	NM_182961.4(SYNE1):c.14204del (p.Gln4735fs)	Pathogenic
1256364	NM_182961.4(SYNE1):c.19046_19048delinsGA (p.Ser6349_Ala6350delinsTer)	Pathogenic
1297576	NM_182961.4(SYNE1):c.24369G>A (p.Trp8123Ter)	Pathogenic
1323664	NM_182961.4(SYNE1):c.25326G>A (p.Trp8442Ter)	Pathogenic
1323666	NM_182961.4(SYNE1):c.13956_13968del (p.Phe4652fs)	Pathogenic
1323667	NM_182961.4(SYNE1):c.10414C>T (p.Arg3472Ter)	Pathogenic
1323668	NM_182961.4(SYNE1):c.5594_5597del (p.Leu1865fs)	Pathogenic
1323669	NM_182961.4(SYNE1):c.3266del (p.Pro1089fs)	Pathogenic
1323670	NM_182961.4(SYNE1):c.352C>T (p.Arg118Ter)	Pathogenic
1335957	NM_182961.4(SYNE1):c.12152G>A (p.Trp4051Ter)	Pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

58469 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:152151611:A:G	L8131P	1.000
6:152151617:A:G	L8129P	1.000
6:152155950:A:G	W7980R	1.000
6:152155950:A:T	W7980R	1.000
6:152164284:A:G	L7890P	1.000
6:152148168:A:G	W8285R	0.999
6:152148168:A:T	W8285R	0.999
6:152151557:A:G	L8149P	0.999
6:152151611:A:T	L8131H	0.999
6:152151632:A:G	L8124P	0.999
6:152151963:A:G	L8103P	0.999
6:152151996:A:G	L8092P	0.999
6:152152006:A:G	W8089R	0.999
6:152152006:A:T	W8089R	0.999
6:152152074:A:G	L8066P	0.999
6:152154977:A:G	L8015P	0.999
6:152155948:C:A	W7980C	0.999
6:152155948:C:G	W7980C	0.999
6:152155961:A:G	L7976P	0.999
6:152156030:A:G	L7953P	0.999
6:152156042:A:G	L7949P	0.999
6:152156048:A:G	L7947P	0.999
6:152156060:A:T	V7943D	0.999
6:152164251:A:G	L7901P	0.999
6:152164314:A:G	L7880P	0.999
6:152176415:A:G	L7869P	0.999
6:152231452:G:T	A6993D	0.999
6:152148166:C:A	W8285C	0.998
6:152148166:C:G	W8285C	0.998
6:152149490:A:G	L8210P	0.998

dbSNP variants (sampled 300 via entrez): RS1000013492 (6:152217788 G>A), RS1000023899 (6:152469887 A>G), RS1000024104 (6:152376396 A>C,G), RS1000032856 (6:152177691 C>T), RS1000041218 (6:152425515 T>A,C), RS1000042618 (6:152296198 A>G), RS1000043733 (6:152460227 G>A), RS1000054560 (6:152350437 G>A), RS1000064534 (6:152217993 C>G,T), RS1000064601 (6:152631275 G>A), RS1000067445 (6:152588577 G>T), RS1000077783 (6:152469710 C>T), RS1000078071 (6:152164680 C>T), RS1000097411 (6:152629459 G>A), RS1000101464 (6:152384098 G>A,T)

Disease associations

OMIM: gene MIM:608441 | disease phenotypes: MIM:610743, MIM:612998, MIM:618484, MIM:108600, MIM:118300, MIM:162500, MIM:270970, MIM:115200, MIM:160500, MIM:213200

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal recessive ataxia, Beauce type	Definitive	Autosomal recessive
Emery-Dreifuss muscular dystrophy 4, autosomal dominant	Strong	Autosomal dominant
arthrogryposis multiplex congenita 3, myogenic type	Strong	Autosomal recessive
autosomal recessive myogenic arthrogryposis multiplex congenita	Supportive	Autosomal recessive
autosomal dominant Emery-Dreifuss muscular dystrophy	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
arthrogryposis multiplex congenita 3, myogenic type	Moderate	AR
autosomal recessive ataxia, Beauce type	Definitive	AR

Mondo (25): autosomal recessive ataxia, Beauce type (MONDO:0012549), Emery-Dreifuss muscular dystrophy 4, autosomal dominant (MONDO:0013071), arthrogryposis multiplex congenita 3, myogenic type (MONDO:0032778), spastic ataxia (MONDO:0017845), Charcot-Marie-Tooth disease type 1E (MONDO:0007311), hereditary neuropathy with liability to pressure palsies (MONDO:0008087), hereditary spherocytosis type 3 (MONDO:0010053), third-degree atrioventricular block (MONDO:0000468), dilated cardiomyopathy 1A (MONDO:0007269), dilated cardiomyopathy (MONDO:0005021), intellectual disability (MONDO:0001071), hereditary ataxia (MONDO:0100309), limb-girdle muscular dystrophy (MONDO:0016971), arthrogryposis syndrome (MONDO:0015225), cardiomyopathy (MONDO:0004994)

Orphanet (22): Emery-Dreifuss muscular dystrophy (Orphanet:261), Autosomal recessive ataxia, Beauce type (Orphanet:88644), Spastic ataxia (Orphanet:316226), Hereditary neuropathy with liability to pressure palsies (Orphanet:640), Charcot-Marie-Tooth disease type 1E (Orphanet:90658), Hereditary spherocytosis (Orphanet:822), Familial dilated cardiomyopathy with conduction defect due to LMNA mutation (Orphanet:300751), Dilated cardiomyopathy (Orphanet:217604), Hereditary ataxia (Orphanet:183518), Limb-girdle muscular dystrophy (Orphanet:263), Arthrogryposis syndrome (Orphanet:109007), Rare cardiomyopathy (Orphanet:167848), Rare ataxia (Orphanet:102002), Primary bone dysplasia (Orphanet:364526), Ependymoma (Orphanet:251636)

HPO phenotypes

139 total (30 of 139 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000020	Urinary incontinence
HP:0000028	Cryptorchidism
HP:0000252	Microcephaly
HP:0000276	Long face
HP:0000343	Long philtrum
HP:0000365	Hearing impairment
HP:0000400	Macrotia
HP:0000467	Neck muscle weakness
HP:0000486	Strabismus
HP:0000508	Ptosis
HP:0000540	Hypermetropia
HP:0000570	Abnormal saccadic eye movements
HP:0000597	Ophthalmoparesis
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000736	Short attention span
HP:0000767	Pectus excavatum
HP:0000912	Sprengel anomaly
HP:0001181	Adducted thumb
HP:0001188	Hand clenching
HP:0001249	Intellectual disability
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001265	Hyporeflexia
HP:0001270	Motor delay
HP:0001271	Polyneuropathy

GWAS associations

37 associations (top):

Study	Trait	p-value
GCST000107_6	Tonometry	8.000000e-06
GCST000641_5	Bipolar disorder or major depressive disorder	1.000000e-06
GCST001135_3	Bipolar disorder	9.000000e-06
GCST001241_14	Bipolar disorder	7.000000e-07
GCST001877_74	Autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia (combined)	4.000000e-09
GCST003262_239	Post bronchodilator FEV1	2.000000e-06
GCST003262_469	Post bronchodilator FEV1	4.000000e-06
GCST003262_470	Post bronchodilator FEV1	2.000000e-06
GCST003262_471	Post bronchodilator FEV1	1.000000e-06
GCST003262_472	Post bronchodilator FEV1	8.000000e-07
GCST003262_473	Post bronchodilator FEV1	9.000000e-07
GCST003262_474	Post bronchodilator FEV1	1.000000e-06
GCST003262_848	Post bronchodilator FEV1	4.000000e-07
GCST003962_4	Bipolar disorder	4.000000e-08
GCST004139_20	Bipolar disorder	7.000000e-08
GCST004549_10	Endometriosis	2.000000e-08
GCST004549_21	Endometriosis	2.000000e-08
GCST004549_25	Endometriosis	7.000000e-08
GCST004549_34	Endometriosis	1.000000e-07
GCST005951_154	Body mass index	1.000000e-09
GCST006288_474	Heel bone mineral density	4.000000e-07
GCST006288_580	Heel bone mineral density	3.000000e-08
GCST006462_2	Uterine fibroids	4.000000e-08
GCST006462_29	Uterine fibroids	9.000000e-24
GCST006462_30	Uterine fibroids	5.000000e-10
GCST006865_8	Bipolar disorder	4.000000e-06
GCST006979_710	Heel bone mineral density	7.000000e-16
GCST006979_711	Heel bone mineral density	2.000000e-22
GCST006979_712	Heel bone mineral density	9.000000e-11
GCST008103_39	Bipolar disorder	1.000000e-07

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004314	forced expiratory volume
EFO:0004340	body mass index
EFO:0009270	heel bone mineral density
EFO:0009963	bipolar I disorder
EFO:0004531	urate measurement
EFO:0004980	appendicular lean mass
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (12)

Descriptor	Name	Tree numbers
D009202	Cardiomyopathies	C14.280.238
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
D002524	Cerebellar Ataxia	C10.228.140.252.190; C10.597.350.090.500; C23.888.592.350.090.200
D004806	Ependymoma	C04.557.465.625.600.380.290; C04.557.470.670.380.290; C04.557.580.625.600.380.290
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D049288	Muscular Dystrophies, Limb-Girdle	C05.651.534.500.280; C10.668.491.175.500.149; C16.320.577.280
C537986	Charcot-Marie-Tooth disease, Type 1E (supp.)
C567831	Emery-Dreifuss Muscular Dystrophy 4 (supp.)
C531684	Hereditary spinal ataxia (supp.)
C564815	Spastic Ataxia (supp.)
C567489	Spherocytosis, Type 3 (supp.)
C536965	Tomaculous neuropathy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	5
trichostatin A	increases expression, affects cotreatment	3
Cadmium Chloride	decreases expression, increases abundance, increases expression	3
bisphenol A	affects cotreatment, decreases methylation, decreases expression, increases methylation	2
sodium arsenite	decreases expression, increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
bisphenol S	increases methylation, affects cotreatment, decreases expression	2
(+)-JQ1 compound	decreases expression	2
Panobinostat	affects cotreatment, increases expression	2
Acetaminophen	decreases expression, increases expression	2
Air Pollutants	affects methylation, increases abundance, increases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Dexamethasone	decreases expression, affects cotreatment	2
Estradiol	affects cotreatment, decreases expression	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cyclosporine	increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
Particulate Matter	affects methylation, increases abundance, increases expression	2
FR900359	increases phosphorylation	1
bufotalin	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	decreases methylation, increases methylation	1
coumarin	decreases phosphorylation	1
cyanoginosin LR	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 telomerase immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_6B25	CMDCl12	Telomerase immortalized cell line	Sex unspecified

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04931693	PHASE4	COMPLETED	PECs Block for Pacemaker Insertion in Children
NCT05666219	PHASE4	WITHDRAWN	Reversal of Complete Heart Block With Aminophylline in Inferior Wall Myocardial Infarction Patients
NCT00374465	PHASE4	UNKNOWN	Therapy With Verapamil or Carvedilol in Chronic Heart Failure
NCT01293903	PHASE4	COMPLETED	Study of Qiliqiangxin Capsule to Treat Dilated Cardiomyopathy
NCT01557140	PHASE4	COMPLETED	A Randomized Trial of Carvedilol in Chronic Chagas Cardiomyopathy
NCT01917149	PHASE4	COMPLETED	Supramaximal Titrated Inhibition of RAAS in Dilated Cardiomyopathy
NCT02115581	PHASE4	COMPLETED	Coenzyme Q10 Supplementation in Children With Idiopathic Dilated Cardiomyopathy
NCT06236022	PHASE4	RECRUITING	The Effects of Sirolimus in Patients With Dilated Cardiomyopathy Infected With Kaposi Sarcoma-associated Virus
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02809131	PHASE3	COMPLETED	Perioperative Antibiotic Therapy to Prevent Cardiac Implantable Electronic Device Infections.
NCT00333827	PHASE3	COMPLETED	Cell Therapy In Dilated Cardiomyopathy
NCT00505154	PHASE3	COMPLETED	Effect of Rosuvastatin on Left Ventricular Remodeling
NCT01223703	PHASE3	COMPLETED	PUFAs and Left Ventricular Function in Heart Failure
NCT01583114	PHASE3	TERMINATED	PREclinical Mutation CARriers From Families With DIlated Cardiomyopathy and ACE Inhibitors
NCT01914081	PHASE3	UNKNOWN	Resveratrol: A Potential Anti- Remodeling Agent in Heart Failure, From Bench to Bedside
NCT02989181	PHASE3	UNKNOWN	Continues Positive Airway Pressure Treatment for Patients With Dilated Cardiomyopathy and Obstructive Sleep Apnea
NCT03439514	PHASE3	TERMINATED	A Study of ARRY-371797 (PF-07265803) in Patients With Symptomatic Dilated Cardiomyopathy Due to a Lamin A/C Gene Mutation
NCT05237323	PHASE3	COMPLETED	Micophenolate Mofetil Versus Azathioprine in Myocarditis
NCT05849766	PHASE3	COMPLETED	Effect of Dapagliflozin on Cardiac Structure, Function and Secondary Mitral Regurgitation in Patients with Left Ventricle Dysfunction
NCT06250257	PHASE3	RECRUITING	Bromocriptine in Dilated Cardiomyopathy Among Women of Reproductive Age
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT01401257	PHASE2	COMPLETED	Phase II, Randomized, Placebo-controlled Trial in Patients With Charcot-marie-tooth Disease Type 1A
NCT00629018	PHASE2	COMPLETED	Safety and Efficacy Study of Stem Cell Transplantation to Treat Dilated Cardiomyopathy
NCT00629096	PHASE2	COMPLETED	Intracoronary Infusion of Autologous Bone Marrow Cells for Treatment of Idiopathic Dilated Cardiomyopathy
NCT00765518	PHASE2	COMPLETED	Use of Ixmyelocel-T (Formerly Cardiac Repair Cell [CRC] Treatment) in Patients With Heart Failure Due to Dilated Cardiomyopathy (IMPACT-DCM)
NCT00847964	PHASE2	COMPLETED	Safety and Feasibility of Algisyl-LVR™ as a Method of Left Ventricular Restoration in Patients With DCM Undergoing Open-heart Surgery
NCT01020968	PHASE2	COMPLETED	Use of Ixmyelocel-T (Formerly Catheter-based Cardiac Repair Cell [CRC]) Treatment in Patients With Heart Failure Due to Dilated Cardiomyopathy
NCT01302171	PHASE2	COMPLETED	Bone Marrow Derived Adult Stem Cells for Dilated Cardiomyopathy
NCT01350310	PHASE2	COMPLETED	Safety and Efficacy Study of Intramyocardial Stem Cell Therapy in Patients With Dilated Cardiomyopathy
NCT02133911	PHASE2	COMPLETED	A Pilot Trial of Ranolazine to Treat Patients With Dilated Cardiomyopathy
NCT03071653	PHASE2	SUSPENDED	Left Cardiac Sympathetic Denervation for Cardiomyopathy Feasibility Pilot Study
NCT03572660	PHASE2	ACTIVE_NOT_RECRUITING	Use of Bone Marrow Derived Stem Cell and G-CSF With Circulatory Assistance in the Treatment of DCM
NCT03775070	PHASE2	COMPLETED	Simvastatin Therapy in Patients With Dilated Cardiomyopathy.
NCT04405804	PHASE2	UNKNOWN	Early Administration of Ivabradine in Children With Heart Failure
NCT05410873	PHASE2	COMPLETED	Examining the Effects of Mitochondrial Oxidative Stress in DCM
NCT06632834	PHASE2	RECRUITING	Outcome-targeted Therapy: Principle and Outcome Evaluation: Clinical Study and Phenotype-genotype Correlation
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study