SYCP1

Summary

SYCP1 (synaptonemal complex protein 1, HGNC:11487) is a protein-coding gene on chromosome 1p13.2, encoding Synaptonemal complex protein 1 (Q15431). Major component of the transverse filaments of synaptonemal complexes, formed between homologous chromosomes during meiotic prophase.

Enables double-stranded DNA binding activity. Involved in protein homotetramerization. Predicted to be located in synaptonemal complex. Predicted to be active in central element; male germ cell nucleus; and transverse filament.

Source: NCBI Gene 6847 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 107 total
• MANE Select transcript: NM_003176

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11487
Approved symbol	SYCP1
Name	synaptonemal complex protein 1
Location	1p13.2
Locus type	gene with protein product
Status	Approved
Aliases	HOM-TES-14, SCP1, CT8
Ensembl gene	ENSG00000198765
Ensembl biotype	protein_coding
OMIM	602162
Entrez	6847

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 5 protein_coding, 5 protein_coding_CDS_not_defined

ENST00000369518, ENST00000369522, ENST00000455987, ENST00000468191, ENST00000477215, ENST00000477590, ENST00000482717, ENST00000493377, ENST00000613524, ENST00000618516

RefSeq mRNA: 3 — MANE Select: NM_003176 NM_001282541, NM_001282542, NM_003176

CCDS: CCDS72840, CCDS879

Canonical transcript exons

ENST00000369522 — 32 exons

Exon	Start	End
ENSE00001434623	114984725	114984868
ENSE00001435186	114856573	114856657
ENSE00001435236	114886125	114886309
ENSE00001435276	114857232	114857275
ENSE00001435389	114857444	114857497
ENSE00001435469	114947246	114947320
ENSE00001435507	114858547	114858711
ENSE00001435559	114944872	114944982
ENSE00001435664	114946289	114946381
ENSE00001436060	114876737	114876810
ENSE00001436172	114878094	114878202
ENSE00001436208	114895448	114895509
ENSE00001436212	114887626	114887693
ENSE00001436276	114885535	114885629
ENSE00001450243	114855441	114855572
ENSE00001450244	114854863	114855018
ENSE00001932302	114994882	114995370
ENSE00003551140	114981336	114981512
ENSE00003571475	114913975	114914045
ENSE00003575402	114860736	114860809
ENSE00003600395	114977557	114977616
ENSE00003600609	114944339	114944455
ENSE00003605712	114926278	114926340
ENSE00003608284	114913033	114913150
ENSE00003612041	114923449	114923530
ENSE00003623064	114994698	114994787
ENSE00003623235	114911479	114911582
ENSE00003627764	114926501	114926563
ENSE00003668202	114910397	114910501
ENSE00003669571	114859743	114859810
ENSE00003676710	114876069	114876138
ENSE00003687378	114874506	114874564

Expression profiles

Bgee: expression breadth ubiquitous, 107 present calls, max score 93.80.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0112 / max 8.5706, expressed in 3 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
4766	0.0112	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	93.80	gold quality
right testis	UBERON:0004534	93.01	gold quality
left testis	UBERON:0004533	92.65	gold quality
male germ cell	CL:0000015	91.43	gold quality
testis	UBERON:0000473	91.26	gold quality
buccal mucosa cell	CL:0002336	90.81	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.73	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.88	gold quality
adult organism	UBERON:0007023	69.23	gold quality
granulocyte	CL:0000094	63.97	gold quality
endometrium epithelium	UBERON:0004811	60.71	gold quality
adrenal tissue	UBERON:0018303	58.81	gold quality
upper leg skin	UBERON:0004262	58.23	silver quality
tibialis anterior	UBERON:0001385	57.44	silver quality
decidua	UBERON:0002450	56.55	gold quality
pancreatic ductal cell	CL:0002079	55.83	silver quality
ventricular zone	UBERON:0003053	55.06	gold quality
leukocyte	CL:0000738	54.99	gold quality
mononuclear cell	CL:0000842	54.13	gold quality
monocyte	CL:0000576	54.10	gold quality
hair follicle	UBERON:0002073	52.43	gold quality
mucosa of urinary bladder	UBERON:0001259	51.55	gold quality
calcaneal tendon	UBERON:0003701	51.40	gold quality
blood	UBERON:0000178	51.31	gold quality
bone marrow cell	CL:0002092	51.03	silver quality
quadriceps femoris	UBERON:0001377	50.88	gold quality
epithelial cell of pancreas	CL:0000083	50.48	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.51

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

33 targeting SYCP1, 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-340-5P	100.00	72.50	4437
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-1179	99.71	68.70	1040
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-802	99.61	67.70	1254
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-4427	99.34	70.33	1854
HSA-MIR-488-5P	99.28	68.12	821
HSA-MIR-382-3P	98.83	67.10	1074
HSA-MIR-760	98.81	66.65	1392
HSA-MIR-7852-3P	98.37	67.98	823
HSA-MIR-633	98.35	69.45	1167
HSA-MIR-12116	97.94	68.91	595

Literature-anchored findings (GeneRIF, showing 7)

• an epitope derived from the cancer testis antigen HOM-TES-14/SCP1 and presented by dendritic cells to circulating CD4+ T cells (PMID:16030183)
• Cancer-Testis Antigen SCP-1 mRNA is expressed in some nasopharyngeal carcinoma. (PMID:17608150)
• SYCP1, cTAGE1, and GTSF1 are expressed in cutaneous T-cell lymphoma, but not in normal skin or benign inflammatory dermatoses. (PMID:24850846)
• crystal structure of the middle part of the human synaptonemal complex protein 1 coiled-coil domain (PMID:26323297)
• Crystal structure of C-terminal coiled-coil domain of SYCP1 reveals non-canonical anti-parallel dimeric structure of transverse filament at the synaptonemal complex. (PMID:27548613)
• SYCP1 has an obligate tetrameric structure in which an N-terminal four-helical bundle bifurcates into two elongated C-terminal dimeric coiled-coils. This building block assembles into a zipper-like lattice through two self-assembly sites. N-terminal sites undergo cooperative head-to-head assembly in the midline, while C-terminal sites interact back to back on the chromosome axis. (PMID:29915389)
• A rare frameshift mutation in SYCP1 is associated with human male infertility. (PMID:35377450)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	sycp1	ENSDARG00000003904
mus_musculus	Sycp1	ENSMUSG00000027855
rattus_norvegicus	Sycp1	ENSRNOG00000016835

Protein

Protein identifiers

Synaptonemal complex protein 1 — Q15431 (reviewed: Q15431)

Alternative names: Cancer/testis antigen 8

All UniProt accessions (4): Q15431, A0A024R0I2, A0A087WZC3, Q5VXJ5

UniProt curated annotations — full annotation on UniProt →

Function. Major component of the transverse filaments of synaptonemal complexes, formed between homologous chromosomes during meiotic prophase. Required for normal assembly of the central element of the synaptonemal complexes. Required for normal centromere pairing during meiosis. Required for normal meiotic chromosome synapsis during oocyte and spermatocyte development and for normal male and female fertility.

Subunit / interactions. Structural component of synaptonemal complexes. Homotetramer that consists of an N-terminal four-helical bundle that bifurcates into two elongated C-terminal dimeric coiled coils. This tetrameric building block potentially self-assembles into a supramolecular zipper-like lattice to mediate meiotic chromosome synapsis. Self-assembly is likely initiated by local proton density at chromosome axis, which is predicted to trigger antiparallel back to back assembly of adjacent C-terminal ends into tetrameric structures that anchor to chromosomal DNA. Then the N-terminal ends are predicted to undergo cooperative antiparallel head to head assembly at the midline of synaptonemal complexes central element to form a zipper-like lattice between properly aligned homologous chromosomes. The nascent synapsis generated by SYCP1 is stabilized through interaction with central element proteins SYCE1 and SYCE2. Interacts (via tetrameric core) with SYCE3; the interaction remodels SYCP1 homotetramers to 2:1 heterotrimers with SYCE3. SYCP1/SYCE3 heterotrimers form lattice assemblies as part of the mature synaptonemal complex via both lateral and head-to-head interactions. Forms a complex with EWSR1, PRDM9, SYCP3 and REC8; complex formation is dependent of phosphorylated form of REC8 and requires PRDM9 bound to hotspot DNA; EWSR1 joins PRDM9 with the chromosomal axis through REC8. Interacts with SPO16.

Subcellular location. Nucleus. Chromosome. Centromere.

Tissue specificity. Testis.

Domain organisation. The molecule is in a coiled coil structure that is formed by 4 polypeptide chains. The N-terminal and C-terminal regions exhibit a prominent seven-residues periodicity.

RefSeq proteins (3): NP_001269470, NP_001269471, NP_003167* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008827	SYCP1	Family

Pfam: PF05483

UniProt features (43 total): sequence conflict 18, mutagenesis site 8, short sequence motif 4, coiled-coil region 4, region of interest 3, helix 3, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
6F5X	X-RAY DIFFRACTION	1.91
4YTO	X-RAY DIFFRACTION	2
6F62	X-RAY DIFFRACTION	2.07
6F63	X-RAY DIFFRACTION	2.15
6F64	X-RAY DIFFRACTION	2.49

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15431-F1	70.75	0.29

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (8):

Position	Phenotype
101–111	impairs self-assembly of n-terminal ends.
105	impairs self-assembly of n-terminal ends; when associated with e-109. abolishes the formation of higher-order heteroolig
109	impairs self-assembly of n-terminal ends; when associated with e-105. abolishes the formation of higher-order heteroolig
679	impairs ph-induced c-terminal tetrameric self-assembly; when associated with a-688.
688	impairs ph-induced c-terminal tetrameric self-assembly; when associated with a-679.
717	impairs ph-induced c-terminal tetrameric self-assembly.
717	enables c-terminal tetrameric self-assembly at ph 8.0; when associated with f-721.
721	enables c-terminal tetrameric self-assembly at ph 8.0; when associated with w-717.

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: 138 (showing top): GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, GOBP_CHROMOSOME_ORGANIZATION, GOBP_PROTEIN_HOMOTETRAMERIZATION, REACTOME_MEIOTIC_SYNAPSIS, GOBP_MALE_GAMETE_GENERATION, WEI_MYCN_TARGETS_WITH_E_BOX, BROWNE_HCMV_INFECTION_48HR_DN, GOBP_SYNAPTONEMAL_COMPLEX_ORGANIZATION, GOBP_ORGANELLE_FISSION, GOBP_NUCLEUS_ORGANIZATION, GOBP_DNA_DAMAGE_RESPONSE, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_CHROMOSOME_ORGANIZATION_INVOLVED_IN_MEIOTIC_CELL_CYCLE, GOBP_DNA_BIOSYNTHETIC_PROCESS, GOBP_SPERMATID_NUCLEUS_DIFFERENTIATION

GO Biological Process (12): meiotic DNA repair synthesis (GO:0000711), homologous chromosome pairing at meiosis (GO:0007129), synaptonemal complex assembly (GO:0007130), reciprocal meiotic recombination (GO:0007131), spermatogenesis (GO:0007283), regulation of protein localization (GO:0032880), sperm DNA condensation (GO:0035092), chiasma assembly (GO:0051026), protein homotetramerization (GO:0051289), cell division (GO:0051301), lateral element assembly (GO:0051878), meiotic cell cycle (GO:0051321)

GO Molecular Function (2): DNA binding (GO:0003677), double-stranded DNA binding (GO:0003690)

GO Cellular Component (9): chromosome, centromeric region (GO:0000775), synaptonemal complex (GO:0000795), central element (GO:0000801), transverse filament (GO:0000802), male germ cell nucleus (GO:0001673), chromosome (GO:0005694), autosome (GO:0030849), condensed nuclear chromosome (GO:0000794), nucleus (GO:0005634)

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 component assembly	3
meiotic cell cycle process	3
chromosome organization involved in meiotic cell cycle	2
homologous chromosome pairing at meiosis	2
synaptonemal complex	2
cellular anatomical structure	2
DNA synthesis involved in DNA repair	1
meiosis I cell cycle process	1
homologous chromosome segregation	1
synaptonemal complex organization	1
meiosis I	1
reciprocal homologous recombination	1
developmental process involved in reproduction	1
male gamete generation	1
intracellular protein localization	1
regulation of localization	1
chromatin organization	1
spermatid nucleus differentiation	1
reciprocal meiotic recombination	1
protein homooligomerization	1
protein tetramerization	1
cellular process	1
synaptonemal complex assembly	1
cell cycle	1
sexual reproduction	1
reproductive process	1
meiotic nuclear division	1
nucleic acid binding	1
DNA binding	1
chromosomal region	1
synaptonemal structure	1
germ cell nucleus	1
intracellular membraneless organelle	1
chromosome	1
nuclear chromosome	1
condensed chromosome	1
nucleus	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1562 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SYCP1	SYCE2	Q6PIF2	996
SYCP1	SYCE1	Q8N0S2	996
SYCP1	SYCP3	Q8IZU3	993
SYCP1	SYCP2	Q9BX26	983
SYCP1	TEX12	Q9BXU0	968
SYCP1	SYCE3	A1L190	938
SYCP1	HORMAD1	Q86X24	868
SYCP1	DAZL	Q92904	827
SYCP1	C14orf39	Q8N1H7	822
SYCP1	REC8	O95072	814
SYCP1	SPO11	Q9Y5K1	810
SYCP1	HORMAD2	Q8N7B1	763
SYCP1	RAD21L1	Q9H4I0	732
SYCP1	STRA8	Q7Z7C7	730
SYCP1	SMC1B	Q8NDV3	714

IntAct

8 interactions, top by confidence:

A	B	Type	Score
HSPA5	SYCP1	psi-mi:“MI:0915”(physical association)	0.400
SYCP1	CREB1	psi-mi:“MI:0915”(physical association)	0.400
Uba1	PIP	psi-mi:“MI:0915”(physical association)	0.400
SYCP1		psi-mi:“MI:0915”(physical association)	0.370
M		psi-mi:“MI:0914”(association)	0.350
Dnajc11	DDX3X	psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350

BioGRID (26): SYCP1 (Affinity Capture-MS), CREB1 (Affinity Capture-MS), SYCP1 (Two-hybrid), SYCP1 (Synthetic Lethality), SYCP1 (Affinity Capture-MS), PSMA8 (Affinity Capture-Western), SYCP1 (Proximity Label-MS), SYCP1 (Affinity Capture-MS), SYCP1 (Reconstituted Complex), SYCP1 (Cross-Linking-MS (XL-MS)), SYCP1 (Cross-Linking-MS (XL-MS)), SYCP1 (Cross-Linking-MS (XL-MS)), SYCP1 (Cross-Linking-MS (XL-MS)), SYCP1 (Cross-Linking-MS (XL-MS)), SYCP1 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A2AUM9, A6PWD2, A7MD70, B1AJZ9, E9Q1U1, O35550, O35551, O75330, O94986, P0CB05, P97779, Q00547, Q03410, Q05D60, Q08DR9, Q13439, Q15276, Q15431, Q3KR99, Q3UPP8, Q498G2, Q4G0S7, Q4R703, Q4R7H3, Q4V7C8, Q53EZ4, Q5U3Z6, Q60563, Q61595, Q62209, Q6NRC9, Q6NRW2, Q6P3P1, Q6TFL3, Q70FJ1, Q80UF4, Q86SQ7, Q8BT07, Q8BVC4, Q8CDI7

Diamond homologs: Q03410, Q15431, Q60563, Q62209

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SYCP1	“form complex”	Synaptonemal_complex	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	92
Likely benign	5
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

4499 predictions. Top by Δscore:

Variant	Effect	Δscore
1:114856571:A:AG	acceptor_gain	1.0000
1:114856572:G:GG	acceptor_gain	1.0000
1:114856572:GA:G	acceptor_gain	1.0000
1:114856572:GAGT:G	acceptor_gain	1.0000
1:114856653:TTCAG:T	donor_loss	1.0000
1:114856654:TCAG:T	donor_loss	1.0000
1:114856655:CAGG:C	donor_loss	1.0000
1:114856656:AG:A	donor_loss	1.0000
1:114856657:G:GC	donor_loss	1.0000
1:114856658:GTAG:G	donor_loss	1.0000
1:114856659:T:A	donor_loss	1.0000
1:114859741:A:AG	acceptor_gain	1.0000
1:114859742:G:GG	acceptor_gain	1.0000
1:114860733:CAG:C	acceptor_loss	1.0000
1:114860735:GGA:G	acceptor_gain	1.0000
1:114860805:GAAAT:G	donor_gain	1.0000
1:114860807:AAT:A	donor_gain	1.0000
1:114860809:TG:T	donor_loss	1.0000
1:114860810:G:GG	donor_gain	1.0000
1:114860810:GTAA:G	donor_loss	1.0000
1:114860811:T:G	donor_loss	1.0000
1:114874501:A:AG	acceptor_gain	1.0000
1:114876068:GAAA:G	acceptor_gain	1.0000
1:114876136:AGT:A	donor_gain	1.0000
1:114876137:GT:G	donor_gain	1.0000
1:114876137:GTG:G	donor_gain	1.0000
1:114876138:TGT:T	donor_gain	1.0000
1:114876139:G:GG	donor_gain	1.0000
1:114876140:T:A	donor_loss	1.0000
1:114876735:A:AG	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000039849 (1:114854518 A>G), RS1000101917 (1:114852161 C>A,G), RS1000109011 (1:114900312 G>A), RS1000141614 (1:114902820 A>T), RS1000174629 (1:114978493 T>C), RS1000216449 (1:114892600 T>G), RS1000221018 (1:114988303 A>C,G), RS1000256642 (1:114956139 C>A,T), RS1000312395 (1:114962384 TAAAC>T), RS1000345546 (1:114969443 G>A), RS1000382648 (1:114859099 T>C), RS1000403344 (1:114962072 G>C), RS1000404820 (1:114878614 G>A), RS1000419364 (1:114969145 G>GA), RS1000435017 (1:114995645 T>C)

Disease associations

OMIM: gene MIM:602162 | 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

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, increases methylation	3
bisphenol F	increases expression, affects cotreatment	1
testosterone enanthate	decreases expression, affects cotreatment	1
terbufos	increases methylation	1
benzo(e)pyrene	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
flavone	increases expression	1
cetrorelix	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	affects cotreatment, increases expression	1
Decitabine	affects expression	1
Acetaminophen	increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Dexamethasone	affects cotreatment, increases expression	1
Fonofos	increases methylation	1
Indomethacin	affects cotreatment, increases expression	1
Lipopolysaccharides	affects cotreatment, increases expression	1
Methapyrilene	increases methylation	1
Parathion	increases methylation	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Desogestrel	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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