SYCE1

Summary

SYCE1 (synaptonemal complex central element protein 1, HGNC:28852) is a protein-coding gene on chromosome 10q26.3, encoding Synaptonemal complex central element protein 1 (Q8N0S2). Major component of the transverse central element of synaptonemal complexes (SCS), formed between homologous chromosomes during meiotic prophase.

This gene encodes a member of the synaptonemal complex, which links homologous chromosomes during prophase I of meiosis. The tripartite structure of the complex is highly conserved amongst metazoans. It consists of two lateral elements and a central region formed by transverse elements and a central element. The protein encoded by this gene localizes to the central element and is required for initiation and elongation of the synapsis. Allelic variants of this gene have been associated with premature ovarian failure and spermatogenic failure. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 93426 — RefSeq curated summary.

At a glance

• Gene–disease (curated): premature ovarian failure 12 (Strong, GenCC) — +2 more curated relationships
• Clinical variants (ClinVar): 86 total — 10 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 17
• MANE Select transcript: NM_001143764

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28852
Approved symbol	SYCE1
Name	synaptonemal complex central element protein 1
Location	10q26.3
Locus type	gene with protein product
Status	Approved
Aliases	bA108K14.6, CT76
Ensembl gene	ENSG00000171772
Ensembl biotype	protein_coding
OMIM	611486
Entrez	93426

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 retained_intron

ENST00000303903, ENST00000343131, ENST00000368517, ENST00000432597, ENST00000479535, ENST00000863035, ENST00000863036, ENST00000863037, ENST00000863038, ENST00000863039

RefSeq mRNA: 3 — MANE Select: NM_001143764 NM_001143763, NM_001143764, NM_130784

CCDS: CCDS44500, CCDS7687

Canonical transcript exons

ENST00000343131 — 13 exons

Exon	Start	End
ENSE00001406300	133554847	133555129
ENSE00003460587	133555351	133555438
ENSE00003496944	133555981	133556047
ENSE00003502031	133557067	133557156
ENSE00003512079	133560091	133560153
ENSE00003519672	133555780	133555903
ENSE00003540200	133558877	133558951
ENSE00003557218	133559301	133559360
ENSE00003592103	133558167	133558214
ENSE00003614034	133557864	133557918
ENSE00003617265	133565457	133565583
ENSE00003622207	133555597	133555707
ENSE00003673197	133556759	133556822

Expression profiles

Bgee: expression breadth ubiquitous, 162 present calls, max score 97.67.

FANTOM5 (CAGE): breadth broad, TPM avg 1.0230 / max 248.9989, expressed in 222 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
112134	0.7095	193
112135	0.2034	55
112138	0.0410	9
112137	0.0388	5
112136	0.0303	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	97.67	gold quality
left testis	UBERON:0004533	97.45	gold quality
testis	UBERON:0000473	94.17	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.70	gold quality
right hemisphere of cerebellum	UBERON:0014890	87.48	gold quality
cerebellar hemisphere	UBERON:0002245	87.26	gold quality
cerebellar cortex	UBERON:0002129	86.98	gold quality
right frontal lobe	UBERON:0002810	86.82	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.24	gold quality
cerebellum	UBERON:0002037	85.10	gold quality
anterior cingulate cortex	UBERON:0009835	84.85	gold quality
Brodmann (1909) area 9	UBERON:0013540	84.82	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	81.49	gold quality
prefrontal cortex	UBERON:0000451	80.93	gold quality
nucleus accumbens	UBERON:0001882	79.34	gold quality
neocortex	UBERON:0001950	78.93	gold quality
frontal cortex	UBERON:0001870	78.84	gold quality
frontal lobe	UBERON:0016525	78.84	gold quality
caudate nucleus	UBERON:0001873	78.57	gold quality
amygdala	UBERON:0001876	78.50	gold quality
putamen	UBERON:0001874	77.70	gold quality
adult organism	UBERON:0007023	77.29	gold quality
hypothalamus	UBERON:0001898	76.54	gold quality
cerebral cortex	UBERON:0000956	76.42	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	74.39	gold quality
brain	UBERON:0000955	74.20	gold quality
forebrain	UBERON:0001890	73.95	gold quality
sperm	CL:0000019	73.35	gold quality
Ammon’s horn	UBERON:0001954	72.23	gold quality
right lobe of liver	UBERON:0001114	71.45	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.99

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 8)

• Given the known function of the SYCE1 gene, we suggest that the nonsense mutation identified accounts for the primary ovarian insufficiency phenotype. (PMID:25062452)
• A mutation in SYCE1 is associated with non-obstructive azoospermia. (PMID:25899990)
• Structural core of SYCE1 is formed by amino acids 25-179, within N-terminal half of protein, which mediates SYCE1 dimerization. This alpha-helical core adopts curved coiled-coil structure of 20-nm length in which two chains are arranged in anti-parallel configuration. Structure is retained within full-length SYCE1, in which long C-termini adopt extended conformations to achieve an elongated molecule of over 50nm in length (PMID:30607510)
• The second mutation of SYCE1 gene associated with autosomal recessive nonobstructive azoospermia. (PMID:31916078)
• Consanguineous Chinese Familial Study Reveals that a Gross Deletion that Includes the SYCE1 Gene Region Is Associated with Premature Ovarian Insufficiency. (PMID:31925770)
• Targeted next-generation sequencing panel screening of 668 Chinese patients with non-obstructive azoospermia. (PMID:33728612)
• Novel copy number variations within SYCE1 caused meiotic arrest and non-obstructive azoospermia. (PMID:35718780)
• Novel Mutations Reduce Expression of Meiotic Regulators SYCE1 and BOLL in Testis of Azoospermic Men from West Bengal, India. (PMID:37957469)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch211-199g17.9	ENSDARG00000076609
mus_musculus	Syce1	ENSMUSG00000025480
rattus_norvegicus	Syce1	ENSRNOG00000024073

Paralogs (1): SYCE1L (ENSG00000205078)

Protein

Protein identifiers

Synaptonemal complex central element protein 1 — Q8N0S2 (reviewed: Q8N0S2)

Alternative names: Cancer/testis antigen 76

All UniProt accessions (3): Q8N0S2, A0A0A0MT28, A0A0B4J1R9

UniProt curated annotations — full annotation on UniProt →

Function. Major component of the transverse central element of synaptonemal complexes (SCS), formed between homologous chromosomes during meiotic prophase. Requires SYCP1 in order to be incorporated into the central element. May have a role in the synaptonemal complex assembly, stabilization and recombination.

Subunit / interactions. Homodimer. Found in a complex with SYCP1 and SYCE2. Interacts with SYCP1, SYCE2 and SYCE3. Interacts with SIX6OS1.

Subcellular location. Nucleus. Chromosome.

Disease relevance. Premature ovarian failure 12 (POF12) [MIM:616947] An ovarian disorder defined as the cessation of ovarian function under the age of 40 years. It is characterized by oligomenorrhea or amenorrhea, in the presence of elevated levels of serum gonadotropins and low estradiol. The disease is caused by variants affecting the gene represented in this entry. Spermatogenic failure, 15 (SPGF15) [MIM:616950] An infertility disorder caused by spermatogenesis defects and characterized by non-obstructive azoospermia due to complete meiotic maturation arrest. SPGF15 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the SYCE family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8N0S2-1	1	yes
Q8N0S2-2	2
Q8N0S2-3	3

RefSeq proteins (3): NP_001137235, NP_001137236, NP_570140 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026676	SYCE1	Family

Pfam: PF15233

UniProt features (12 total): sequence variant 3, splice variant 3, region of interest 2, chain 1, sequence conflict 1, coiled-coil region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N0S2-F1	79.04	0.58

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: 102 (showing top): GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, GOBP_CHROMOSOME_ORGANIZATION, REACTOME_MEIOTIC_SYNAPSIS, GOBP_SYNAPTONEMAL_COMPLEX_ORGANIZATION, GOBP_ORGANELLE_FISSION, GOBP_CHROMOSOME_ORGANIZATION_INVOLVED_IN_MEIOTIC_CELL_CYCLE, LYF1_01, GOBP_HOMOLOGOUS_CHROMOSOME_SEGREGATION, GOBP_MEIOTIC_CELL_CYCLE_PROCESS, GOBP_HOMOLOGOUS_CHROMOSOME_PAIRING_AT_MEIOSIS, GOBP_NUCLEAR_CHROMOSOME_SEGREGATION, GOBP_MEIOTIC_CELL_CYCLE, GOBP_CELL_DIVISION, GOBP_CELL_CYCLE_PROCESS, GOBP_DNA_METABOLIC_PROCESS

GO Biological Process (4): synaptonemal complex assembly (GO:0007130), cell division (GO:0051301), meiotic cell cycle (GO:0051321), synaptonemal complex organization (GO:0070193)

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

GO Cellular Component (5): synaptonemal complex (GO:0000795), central element (GO:0000801), chromosome (GO:0005694), 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
cellular anatomical structure	2
homologous chromosome pairing at meiosis	1
cellular component assembly	1
chromosome organization involved in meiotic cell cycle	1
synaptonemal complex organization	1
cellular process	1
cell cycle	1
sexual reproduction	1
reproductive process	1
meiotic nuclear division	1
chromosome organization	1
binding	1
synaptonemal structure	1
synaptonemal complex	1
intracellular membraneless organelle	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

988 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SYCE1	SYCE2	Q6PIF2	999
SYCE1	SYCP1	Q15431	996
SYCE1	TEX12	Q9BXU0	987
SYCE1	SYCE3	A1L190	973
SYCE1	SYCP3	Q8IZU3	883
SYCE1	DAZL	Q92904	879
SYCE1	C14orf39	Q8N1H7	863
SYCE1	HORMAD1	Q86X24	833
SYCE1	STAG3	Q9UJ98	828
SYCE1	SYCP2	Q9BX26	810
SYCE1	SPO11	Q9Y5K1	743
SYCE1	REC8	O95072	734
SYCE1	HORMAD2	Q8N7B1	723
SYCE1	MEI1	Q5TIA1	717
SYCE1	MEIOB	Q8N635	700

IntAct

203 interactions, top by confidence:

A	B	Type	Score
SYCE1	BFSP2	psi-mi:“MI:0915”(physical association)	0.810
BFSP2	SYCE1	psi-mi:“MI:0915”(physical association)	0.810
SYCE1	TPM3	psi-mi:“MI:0915”(physical association)	0.740
TPM3	SYCE1	psi-mi:“MI:0915”(physical association)	0.740
SYCE1	ALOX5	psi-mi:“MI:0915”(physical association)	0.720
SYCE1	TSG101	psi-mi:“MI:0915”(physical association)	0.720
NME7	SYCE1	psi-mi:“MI:0915”(physical association)	0.720
ALOX5	SYCE1	psi-mi:“MI:0915”(physical association)	0.720
SYCE1	NME7	psi-mi:“MI:0915”(physical association)	0.720
SYCE1	CBY2	psi-mi:“MI:0915”(physical association)	0.700
CBY2	SYCE1	psi-mi:“MI:0915”(physical association)	0.700

BioGRID (143): SYCE1 (Two-hybrid), SYCE1 (Two-hybrid), SYCE1 (Two-hybrid), SYCE1 (Two-hybrid), SYCE1 (Two-hybrid), SYCE1 (Two-hybrid), SYCE1 (Two-hybrid), SYCE1 (Two-hybrid), SYCE1 (Two-hybrid), SYCE1 (Two-hybrid), SYCE1 (Two-hybrid), SYCE1 (Two-hybrid), SYCE1 (Two-hybrid), SYCE1 (Two-hybrid), SYCE1 (Two-hybrid)

ESM2 similar proteins: A1L443, A2IDD5, A4IFI1, A6NJZ7, A6NNL0, A6NNM3, A8MT33, B1AL46, D3Z5T1, O95153, Q2M3G4, Q2T9R2, Q3TVI4, Q3TYX8, Q49AM3, Q4KLY2, Q569K6, Q5JTD0, Q5JXC2, Q5SSQ6, Q5SW24, Q5VT03, Q5VZR2, Q6ZNE9, Q7TN08, Q7TNF8, Q7Z591, Q80VJ8, Q810H6, Q811T9, Q86SX3, Q8C963, Q8CB62, Q8CII8, Q8IVF1, Q8IXR5, Q8N0S2, Q8N137, Q8N205, Q8N6L0

Diamond homologs: A8MT33, Q32LK9, Q4R7J8, Q5D525, Q5XHZ2, Q8N0S2, Q9D495

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SYCE1	“form complex”	Synaptonemal_complex	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	1
Uncertain significance	42
Likely benign	15
Benign	13

Top pathogenic / likely-pathogenic (11)

Variant ID	HGVS	Classification
1071187	NM_001143764.3(SYCE1):c.449_452del (p.Lys150fs)	Pathogenic
226122	NM_001143764.3(SYCE1):c.721C>T (p.Gln241Ter)	Pathogenic
226420	NM_001143764.3(SYCE1):c.197-2A>G	Pathogenic
4796749	SYCE1, IVS4, G-A, +1	Pathogenic
4796750	SYCE1, 2-BP DEL, 689TT	Pathogenic
4796751	NM_001143764.3(SYCE1):c.475G>A (p.Glu159Lys)	Pathogenic
4796752	NM_001143764.3(SYCE1):c.271+2T>C	Pathogenic
4796753	SYCE1, ARG52TER	Pathogenic
4796754	SYCE1, 1-BP DEL, NT675	Pathogenic
643186	NM_001143764.3(SYCE1):c.455_456del (p.Arg152fs)	Pathogenic
4796755	NM_001143764.3(SYCE1):c.271+1G>A	Likely pathogenic

SpliceAI

2037 predictions. Top by Δscore:

Variant	Effect	Δscore
10:133555345:GCTTA:G	donor_loss	1.0000
10:133555346:CTTAC:C	donor_loss	1.0000
10:133555347:TTA:T	donor_loss	1.0000
10:133555348:TA:T	donor_loss	1.0000
10:133555350:C:A	donor_loss	1.0000
10:133555434:TCAGC:T	acceptor_gain	1.0000
10:133555435:CAGC:C	acceptor_gain	1.0000
10:133555435:CAGCC:C	acceptor_gain	1.0000
10:133555436:AGC:A	acceptor_gain	1.0000
10:133555437:GC:G	acceptor_gain	1.0000
10:133555438:CC:C	acceptor_gain	1.0000
10:133555439:C:A	acceptor_loss	1.0000
10:133555439:C:CC	acceptor_gain	1.0000
10:133555444:C:CT	acceptor_gain	1.0000
10:133555445:A:T	acceptor_gain	1.0000
10:133555453:G:C	acceptor_gain	1.0000
10:133555453:G:GC	acceptor_gain	1.0000
10:133555558:T:TA	donor_gain	1.0000
10:133555594:CACCT:C	donor_loss	1.0000
10:133555596:C:CT	donor_loss	1.0000
10:133555596:CCT:C	donor_gain	1.0000
10:133555703:GCTGC:G	acceptor_loss	1.0000
10:133555704:CTGC:C	acceptor_gain	1.0000
10:133555705:TGC:T	acceptor_gain	1.0000
10:133555706:GCCTG:G	acceptor_loss	1.0000
10:133555708:CTGG:C	acceptor_loss	1.0000
10:133555709:T:G	acceptor_loss	1.0000
10:133555778:A:AC	donor_gain	1.0000
10:133555779:C:CC	donor_gain	1.0000
10:133555779:CA:C	donor_gain	1.0000

AlphaMissense

2310 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:133556813:G:C	F158L	0.961
10:133556813:G:T	F158L	0.961
10:133556815:A:G	F158L	0.961
10:133559321:C:G	R59P	0.948
10:133559301:C:G	A66P	0.946
10:133555809:A:C	F230L	0.937
10:133555809:A:T	F230L	0.937
10:133555811:A:G	F230L	0.937
10:133556793:A:G	L165P	0.920
10:133559330:A:G	L56P	0.913
10:133555800:G:C	S233R	0.912
10:133555800:G:T	S233R	0.912
10:133555802:T:G	S233R	0.912
10:133555992:A:G	L195P	0.912
10:133555679:C:G	A250P	0.910
10:133556802:A:G	L162P	0.903
10:133555699:A:G	F243S	0.889
10:133558193:A:G	L98P	0.885
10:133560120:A:G	L36S	0.881
10:133556822:C:A	R155S	0.875
10:133556822:C:G	R155S	0.875
10:133557903:A:G	L112P	0.873
10:133559318:A:G	I60T	0.867
10:133555793:C:G	A236P	0.865
10:133557912:A:G	L109P	0.863
10:133560099:A:G	L43P	0.859
10:133558897:A:G	L84P	0.852
10:133555698:A:C	F243L	0.845
10:133555698:A:T	F243L	0.845
10:133555700:A:G	F243L	0.845

dbSNP variants (sampled 300 via entrez): RS1000229351 (10:133560646 T>A,C), RS1000281659 (10:133560363 C>T), RS1000781575 (10:133565727 G>C), RS1001129156 (10:133565867 T>C), RS1001811851 (10:133566580 G>A), RS1001851983 (10:133555256 G>A,C), RS1002015005 (10:133565333 C>T), RS1002256007 (10:133556131 T>C), RS1002544748 (10:133565620 G>A,C), RS1002674477 (10:133560342 C>A,T), RS1002818355 (10:133565713 A>C,G), RS1002940418 (10:133553789 C>G), RS1003250408 (10:133564773 C>T), RS1003301105 (10:133564608 G>A,T), RS1003326471 (10:133553447 A>T)

Disease associations

OMIM: gene MIM:611486 | disease phenotypes: MIM:616947, MIM:616950

GenCC curated gene-disease

Disease	Classification	Inheritance
premature ovarian failure 12	Strong	Autosomal recessive
spermatogenic failure 15	Strong	Autosomal recessive
male infertility with azoospermia or oligozoospermia due to single gene mutation	Supportive	Autosomal dominant

Mondo (3): premature ovarian failure 12 (MONDO:0014844), spermatogenic failure 15 (MONDO:0014847), (MONDO:0018393)

Orphanet (0):

HPO phenotypes

17 total (17 of 17 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000027	Azoospermia
HP:0000118	Phenotypic abnormality
HP:0000568	Microphthalmia
HP:0000786	Primary amenorrhea
HP:0000837	Increased circulating gonadotropin level
HP:0003251	Male infertility
HP:0007754	Macular dystrophy
HP:0008669	Abnormal spermatogenesis
HP:0008734	Decreased testicular size
HP:0011462	Young adult onset
HP:0011961	Non-obstructive azoospermia
HP:0011962	Obstructive azoospermia
HP:0030087	Abnormal circulating testosterone concentration
HP:0030345	Abnormal circulating luteinizing hormone concentration
HP:0030346	Abnormal circulating follicle-stimulating hormone concentration
HP:0031038	Spermatogenesis maturation arrest

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

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
CGP 52608	affects binding, increases reaction	1
Benzo(a)pyrene	affects methylation	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04009473	PHASE1/PHASE2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation