SYNC

Summary

SYNC (syncoilin, intermediate filament protein, HGNC:28897) is a protein-coding gene on chromosome 1p35.1, encoding Syncoilin (Q9H7C4). Atypical type III intermediate filament (IF) protein that may play a supportive role in the efficient coupling of mechanical stress between the myofibril and fiber exterior.

This gene encodes a member of the intermediate filament family which contains an N-terminal head domain, followed by a central coiled-coil region and a short C-terminal tail. The protein is highly expressed in skeletal and cardiac muscle. The protein links the dystrophin associated protein complex (DAPC) to desmin filaments in muscle and may have a structural role in striated muscle. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 81493 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 82 total
• MANE Select transcript: NM_030786

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28897
Approved symbol	SYNC
Name	syncoilin, intermediate filament protein
Location	1p35.1
Locus type	gene with protein product
Status	Approved
Aliases	SYNCOILIN
Ensembl gene	ENSG00000162520
Ensembl biotype	protein_coding
OMIM	611750
Entrez	81493

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000373484, ENST00000409190, ENST00000417633, ENST00000426909, ENST00000854989, ENST00000854990, ENST00000947460, ENST00000947461

RefSeq mRNA: 2 — MANE Select: NM_030786 NM_001161708, NM_030786

CCDS: CCDS367, CCDS53294

Canonical transcript exons

ENST00000409190 — 5 exons

Exon	Start	End
ENSE00001066001	32684258	32684382
ENSE00001318236	32684010	32684089
ENSE00001637678	32694865	32696044
ENSE00001870593	32702608	32702770
ENSE00001931692	32679906	32681860

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 96.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.9489 / max 243.7578, expressed in 1058 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
11552	5.0886	1008
11553	0.3895	244
11550	0.2123	104
11551	0.1657	59
11548	0.0626	18
11549	0.0301	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
biceps brachii	UBERON:0001507	96.00	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	95.78	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	95.62	gold quality
vastus lateralis	UBERON:0001379	95.20	gold quality
gastrocnemius	UBERON:0001388	95.05	gold quality
muscle of leg	UBERON:0001383	94.62	gold quality
muscle organ	UBERON:0001630	94.60	gold quality
quadriceps femoris	UBERON:0001377	94.54	gold quality
diaphragm	UBERON:0001103	94.31	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.22	gold quality
skeletal muscle tissue	UBERON:0001134	94.10	gold quality
gluteal muscle	UBERON:0002000	93.19	gold quality
triceps brachii	UBERON:0001509	92.98	gold quality
deltoid	UBERON:0001476	91.76	gold quality
smooth muscle tissue	UBERON:0001135	91.60	gold quality
muscle tissue	UBERON:0002385	91.35	gold quality
blood vessel layer	UBERON:0004797	91.07	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.81	gold quality
lower esophagus muscularis layer	UBERON:0035833	90.45	gold quality
lower esophagus	UBERON:0013473	90.38	gold quality
buccal mucosa cell	CL:0002336	90.36	gold quality
mucosa of stomach	UBERON:0001199	90.30	gold quality
tibialis anterior	UBERON:0001385	89.41	gold quality
thoracic aorta	UBERON:0001515	89.27	gold quality
ascending aorta	UBERON:0001496	89.11	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	89.00	gold quality
descending thoracic aorta	UBERON:0002345	88.76	gold quality
right coronary artery	UBERON:0001625	88.15	gold quality
cranial nerve II	UBERON:0000941	87.11	gold quality
aorta	UBERON:0000947	87.04	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-112	yes	7.34
E-ANND-3	yes	3.22

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

133 targeting SYNC, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-5696	99.98	72.36	4487
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778

Literature-anchored findings (GeneRIF, showing 4)

• the result of this study raise the possibility that mutations in the gene encoding for syncoilin may underlie some forms of muscle disease. (PMID:16124004)
• The differences in human syncoilin and beta-synemin mRNA ratios between Duchenne muscular dystrophy and normal muscles were not statistically significant (PMID:20199207)
• Syncoilin modulates peripherin filament network formation. (PMID:20587592)
• Elevated SYNC Expression Is Associated with Gastric Tumorigenesis and Infiltration of M2-Polarized Macrophages in the Gastric Tumor Immune Microenvironment. (PMID:33734892)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	sync	ENSDARG00000035944
mus_musculus	Sync	ENSMUSG00000001333
rattus_norvegicus	Sync	ENSRNOG00000008118

Protein

Protein identifiers

Syncoilin — Q9H7C4 (reviewed: Q9H7C4)

Alternative names: Syncoilin intermediate filament 1, Syncoilin-1

All UniProt accessions (3): C9JSS1, C9JTN4, Q9H7C4

UniProt curated annotations — full annotation on UniProt →

Function. Atypical type III intermediate filament (IF) protein that may play a supportive role in the efficient coupling of mechanical stress between the myofibril and fiber exterior. May facilitate lateral force transmission during skeletal muscle contraction. Does not form homofilaments nor heterofilaments with other IF proteins.

Subunit / interactions. May link the dystrophin-associated glycoprotein complex (DAPC) to intracellular desmin (DES) filaments. Interacts with DES and DTNA.

Subcellular location. Cytoplasm. Perinuclear region.

Induction. Up-regulated at the sarcolemma in individuals with various forms of neuromuscular disease.

Similarity. Belongs to the intermediate filament family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H7C4-1	1	yes
Q9H7C4-2	2

RefSeq proteins (2): NP_001155180, NP_110413* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027702	Syncoilin	Family
IPR039008	IF_rod_dom	Domain

Pfam: PF00038

UniProt features (23 total): region of interest 10, sequence conflict 4, compositionally biased region 3, modified residue 3, chain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H7C4-F1	73.48	0.53

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 (3): 26, 34, 325

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 117 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, AAGCAAT_MIR137, GOBP_INTERMEDIATE_FILAMENT_BASED_PROCESS, GCM_ZNF198, GCM_PPM1D, CAGCTG_AP4_Q5, BLALOCK_ALZHEIMERS_DISEASE_UP, KYNG_DNA_DAMAGE_BY_GAMMA_RADIATION, GCM_SUFU, MYB_Q3, MODULE_284, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, KIM_WT1_TARGETS_12HR_UP, GRADE_COLON_AND_RECTAL_CANCER_DN, TGCCTTA_MIR124A

GO Biological Process (1): intermediate filament-based process (GO:0045103)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (7): cytosol (GO:0005829), intermediate filament (GO:0005882), Z disc (GO:0030018), neuromuscular junction (GO:0031594), sarcolemma (GO:0042383), perinuclear region of cytoplasm (GO:0048471), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoplasm	2
cellular process	1
binding	1
intermediate filament cytoskeleton	1
polymeric cytoskeletal fiber	1
I band	1
synapse	1
plasma membrane	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

740 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SYNC	DTNA	Q9Y4J8	987
SYNC	DES	P17661	825
SYNC	DMD	P11532	785
SYNC	SYNM	O15061	781
SYNC	DTNB	O60941	741
SYNC	SSPN	Q14714	596
SYNC	PLEC	Q15149	582
SYNC	VCL	P18206	552
SYNC	RYR1	P21817	546
SYNC	FLNC	Q14315	532
SYNC	MYOT	Q9UBF9	455
SYNC	INA	Q16352	422
SYNC	GALE	Q14376	402
SYNC	DAG1	Q14118	397
SYNC	SYPL2	Q5VXT5	387

IntAct

51 interactions, top by confidence:

A	B	Type	Score
VIM	NEFL	psi-mi:“MI:0914”(association)	0.840
TUBGCP5	TUBG1	psi-mi:“MI:0914”(association)	0.840
GFAP	VIM	psi-mi:“MI:0914”(association)	0.830
SYNC	VIM	psi-mi:“MI:0915”(physical association)	0.740
SYNC	GFAP	psi-mi:“MI:0915”(physical association)	0.670
SYNC	NEFL	psi-mi:“MI:0915”(physical association)	0.670
MAGEE1	MCC	psi-mi:“MI:0914”(association)	0.670
SYNC	ACTA1	psi-mi:“MI:0915”(physical association)	0.560
SYNC	ATP1A3	psi-mi:“MI:0915”(physical association)	0.560
	SYNC	psi-mi:“MI:0915”(physical association)	0.560
SYNC	PECAM1	psi-mi:“MI:0915”(physical association)	0.560
PLD1	SYNC	psi-mi:“MI:0915”(physical association)	0.560
RAB5A	SYNC	psi-mi:“MI:0915”(physical association)	0.560
SYNC	WFS1	psi-mi:“MI:0915”(physical association)	0.560
SYNC	KIF1B	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (105): SYNC (Affinity Capture-MS), SYNC (Affinity Capture-MS), SYNC (Affinity Capture-MS), PRPH (Affinity Capture-MS), DES (Affinity Capture-MS), CCDC136 (Affinity Capture-MS), TJAP1 (Affinity Capture-MS), MAP3K7 (Affinity Capture-MS), APC (Affinity Capture-MS), CEP55 (Affinity Capture-MS), INA (Affinity Capture-MS), SYNM (Affinity Capture-MS), NEFM (Affinity Capture-MS), MCC (Affinity Capture-MS), IKBKG (Affinity Capture-MS)

ESM2 similar proteins: A4IFI1, A5D8V7, A8MT33, D3Z5T1, E1U8D0, F1MGG3, O60826, O94964, P0CW27, P86182, Q02435, Q1RMI8, Q2M329, Q32LK9, Q32LQ1, Q494V2, Q4R7J8, Q4R8V8, Q569K6, Q5D525, Q5ND29, Q5SPX1, Q5SXM2, Q5XFX8, Q62036, Q6ZNE9, Q6ZQ12, Q6ZQ29, Q7Z6P3, Q80VJ8, Q80VR2, Q8C0G2, Q8CB62, Q8CB87, Q8N0S2, Q8N137, Q95LS7, Q96KN7, Q96NA2, Q9CR92

Diamond homologs: Q9EPM5, Q9H7C4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 33 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
intermediate filament organization	7	52.7×	2e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	68
Likely benign	9
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1032 predictions. Top by Δscore:

Variant	Effect	Δscore
1:32684256:A:AC	donor_gain	1.0000
1:32684257:C:CC	donor_gain	1.0000
1:32684260:A:AC	donor_gain	1.0000
1:32684261:T:C	donor_gain	1.0000
1:32684288:AG:A	donor_gain	1.0000
1:32684295:G:C	donor_gain	1.0000
1:32694863:AC:A	donor_gain	1.0000
1:32694864:CC:C	donor_gain	1.0000
1:32696045:C:CC	acceptor_gain	1.0000
1:32696045:CTGCA:C	acceptor_loss	1.0000
1:32696046:T:A	acceptor_loss	1.0000
1:32680613:GT:G	donor_gain	0.9900
1:32694861:CTA:C	donor_loss	0.9900
1:32694862:TACC:T	donor_loss	0.9900
1:32694863:ACC:A	donor_loss	0.9900
1:32694864:C:T	donor_loss	0.9900
1:32694897:G:A	donor_gain	0.9900
1:32696040:TTTTC:T	acceptor_gain	0.9900
1:32696041:TTTC:T	acceptor_gain	0.9900
1:32696042:TTC:T	acceptor_gain	0.9900
1:32696043:TC:T	acceptor_gain	0.9900
1:32696044:CC:C	acceptor_gain	0.9900
1:32684289:G:C	donor_gain	0.9800
1:32694870:A:AC	donor_gain	0.9800
1:32694871:C:CC	donor_gain	0.9800
1:32694927:T:TA	donor_gain	0.9800
1:32702602:TCCTA:T	donor_loss	0.9800
1:32702603:CCTA:C	donor_loss	0.9800
1:32702604:CTACC:C	donor_loss	0.9800
1:32702605:TACCT:T	donor_loss	0.9800

AlphaMissense

3149 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:32695511:A:G	L196P	0.994
1:32695499:A:G	L200P	0.993
1:32695562:A:G	F179S	0.991
1:32695532:A:G	L189P	0.989
1:32695561:G:C	F179L	0.989
1:32695561:G:T	F179L	0.989
1:32695563:A:G	F179L	0.989
1:32694890:C:G	R403P	0.988
1:32695437:C:G	A221P	0.988
1:32695562:A:C	F179C	0.987
1:32695422:C:G	A226P	0.986
1:32695416:C:G	A228P	0.984
1:32695545:C:G	A185P	0.983
1:32694923:A:G	L392P	0.981
1:32695361:A:G	L246P	0.981
1:32695487:C:G	R204P	0.980
1:32695490:A:G	L203P	0.978
1:32695409:A:G	L230P	0.977
1:32694944:A:G	L385P	0.975
1:32695369:C:A	K243N	0.975
1:32695369:C:G	K243N	0.975
1:32695357:G:C	F247L	0.974
1:32695357:G:T	F247L	0.974
1:32695359:A:G	F247L	0.974
1:32684294:A:G	L441P	0.972
1:32684270:A:G	L449P	0.968
1:32695345:C:A	K251N	0.968
1:32695345:C:G	K251N	0.968
1:32695519:C:A	R193S	0.967
1:32695519:C:G	R193S	0.967

dbSNP variants (sampled 300 via entrez): RS1000033074 (1:32681044 A>G), RS1000406000 (1:32703451 G>A), RS1000521395 (1:32679549 ACT>A), RS1000572315 (1:32697723 A>G), RS1000691025 (1:32691794 T>A), RS1000706858 (1:32685312 A>G), RS1000729534 (1:32701204 C>T), RS1000994083 (1:32685710 C>T), RS1001036403 (1:32700982 C>T), RS1001039179 (1:32682440 T>A,C), RS1001665910 (1:32688333 AATT>A), RS1001703068 (1:32682524 G>A), RS1002085837 (1:32704745 G>A,T), RS1002265722 (1:32687056 A>T), RS1002370029 (1:32693024 A>C)

Disease associations

OMIM: gene MIM:611750 | 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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	6
Benzo(a)pyrene	decreases expression, increases expression, affects expression, affects methylation	5
Aflatoxin B1	affects expression, increases expression	3
potassium chromate(VI)	affects cotreatment, decreases expression	2
bisphenol S	increases expression, affects cotreatment, decreases expression	2
Air Pollutants	decreases expression, increases abundance	2
Cyclosporine	decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
sotorasib	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression, increases abundance	1
butyraldehyde	decreases expression	1
triadimefon	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
avobenzone	decreases expression	1
chromium hexavalent ion	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
trametinib	increases expression, affects cotreatment	1
(+)-JQ1 compound	decreases expression	1
NVP-BKM120	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1

Clinical trials (associated diseases)

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