SYCE3

Summary

SYCE3 (synaptonemal complex central element protein 3, HGNC:35245) is a protein-coding gene on chromosome 22q13.33, encoding Synaptonemal complex central element protein 3 (A1L190). Major component of the transverse central element of synaptonemal complexes (SCS), formed between homologous chromosomes during meiotic prophase.

Predicted to be involved in reciprocal meiotic recombination; spermatogenesis; and synaptonemal complex assembly. Predicted to act upstream of or within positive regulation of apoptotic process; positive regulation of developmental process; and positive regulation of reproductive process. Predicted to be located in chromosome and nucleus. Predicted to be active in central element.

Source: NCBI Gene 644186 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 14 total
• MANE Select transcript: NM_001123225

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:35245
Approved symbol	SYCE3
Name	synaptonemal complex central element protein 3
Location	22q13.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000217442
Ensembl biotype	protein_coding
OMIM	615775
Entrez	644186

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000402753, ENST00000406915

RefSeq mRNA: 1 — MANE Select: NM_001123225 NM_001123225

CCDS: CCDS46733

Canonical transcript exons

ENST00000406915 — 3 exons

Exon	Start	End
ENSE00001551934	50551112	50551402
ENSE00001560608	50556297	50556405
ENSE00001560886	50562858	50562919

Expression profiles

Bgee: expression breadth ubiquitous, 155 present calls, max score 97.83.

FANTOM5 (CAGE): breadth broad, TPM avg 0.4790 / max 146.6026, expressed in 186 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
194789	0.3504	131
194788	0.1126	37
194790	0.0160	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	97.83	gold quality
right testis	UBERON:0004534	97.75	gold quality
testis	UBERON:0000473	94.92	gold quality
sperm	CL:0000019	94.70	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.27	gold quality
adult organism	UBERON:0007023	88.30	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.71	gold quality
epithelial cell of pancreas	CL:0000083	74.04	gold quality
nasal cavity epithelium	UBERON:0005384	66.81	gold quality
cardiac muscle of right atrium	UBERON:0003379	66.72	gold quality
left ventricle myocardium	UBERON:0006566	66.43	gold quality
granulocyte	CL:0000094	64.52	gold quality
myocardium	UBERON:0002349	64.30	gold quality
upper arm skin	UBERON:0004263	64.05	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	63.01	gold quality
secondary oocyte	CL:0000655	62.25	gold quality
islet of Langerhans	UBERON:0000006	61.58	gold quality
substantia nigra	UBERON:0002038	61.52	gold quality
putamen	UBERON:0001874	61.35	gold quality
quadriceps femoris	UBERON:0001377	60.98	gold quality
hypothalamus	UBERON:0001898	60.98	gold quality
amygdala	UBERON:0001876	60.70	gold quality
midbrain	UBERON:0001891	60.60	gold quality
vastus lateralis	UBERON:0001379	60.26	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	60.10	gold quality
nasal cavity mucosa	UBERON:0001826	60.03	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	59.86	gold quality
adult mammalian kidney	UBERON:0000082	59.38	gold quality
spinal cord	UBERON:0002240	59.22	gold quality
nucleus accumbens	UBERON:0001882	58.75	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	31.28
E-ANND-3	no	1.67

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

4 targeting SYCE3, 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-3658	99.96	73.87	4379
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-6821-3P	95.21	66.79	578

Literature-anchored findings (GeneRIF, showing 1)

• Cloning and expression analysis of a similar gene in mouse. (PMID:19323366)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Syce3	ENSMUSG00000078938
rattus_norvegicus	Syce3	ENSRNOG00000042056

Protein

Protein identifiers

Synaptonemal complex central element protein 3 — A1L190 (reviewed: A1L190)

Alternative names: Testis highly expressed gene 2 protein

All UniProt accessions (1): A1L190

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. Required for the assembly of the central element of the synaptonemal complex during meiosis, via remodeling of SYCP1 lattice structures and promoting recruitment of SYCE2-TEX12 and SYCE1-SIX60S1 complexes. Required for chromosome loading of the central element-specific SCS proteins, and for initiating synapsis between homologous chromosomes. Chromosome loading appears to require SYCP1. Required for fertility and normal testis development.

Subunit / interactions. Homodimer. Can form higher-order homooligomers. Interacts with SYCP1 (via tetrameric core); 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. Interacts with the SYCE1-SIX6OS1 complex; the interaction recruits the SYCE1-SIX6OS1 complex to the central element of the synaptonemal complex. Interacts with the SYCE2-TEX12 complex; the interaction promotes fibrous assembly of SYCE2-TEX12 as part of the synaptonemal complex central element. Interacts with SYCE1. Interacts with SYCE2. Interacts with proteasome subunit PSMA8; to participate in meiosis progression during spermatogenesis. Interacts with SPO16.

Subcellular location. Nucleus. Chromosome.

RefSeq proteins (1): NP_001116697* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028145	Synaptonemal_3	Family

Pfam: PF15191

UniProt features (6 total): mutagenesis site 3, chain 1, coiled-coil region 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6H86	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A1L190-F1	93.66	0.85

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 (3):

Position	Phenotype
41	abolishes formation of higher-order homooligomers; when associated with e-44. abolishes interaction between sycp1/syce3
44	abolishes formation of higher-order homooligomers; when associated with e-41. abolishes interaction between sycp1/syce3
53	promotes formation of higher-order homooligomers.

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: 53 (showing top): GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, GOBP_CHROMOSOME_ORGANIZATION, REACTOME_MEIOTIC_SYNAPSIS, GOBP_MALE_GAMETE_GENERATION, GOBP_SYNAPTONEMAL_COMPLEX_ORGANIZATION, GOBP_ORGANELLE_FISSION, GOBP_CHROMOSOME_ORGANIZATION_INVOLVED_IN_MEIOTIC_CELL_CYCLE, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, 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, chr22q13

GO Biological Process (10): apoptotic process (GO:0006915), synaptonemal complex assembly (GO:0007130), reciprocal meiotic recombination (GO:0007131), spermatogenesis (GO:0007283), ectopic germ cell programmed cell death (GO:0035234), positive regulation of apoptotic process (GO:0043065), positive regulation of developmental process (GO:0051094), cell division (GO:0051301), positive regulation of reproductive process (GO:2000243), meiotic cell cycle (GO:0051321)

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

GO Cellular Component (3): central element (GO:0000801), nucleus (GO:0005634), chromosome (GO:0005694)

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
developmental process involved in reproduction	2
positive regulation of biological process	2
reproductive process	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
homologous chromosome pairing at meiosis	1
cellular component assembly	1
chromosome organization involved in meiotic cell cycle	1
synaptonemal complex organization	1
meiosis I	1
reciprocal homologous recombination	1
meiotic cell cycle process	1
male gamete generation	1
programmed cell death involved in cell development	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
developmental process	1
regulation of developmental process	1
cellular process	1
regulation of reproductive process	1
cell cycle	1
sexual reproduction	1
meiotic nuclear division	1
binding	1
synaptonemal complex	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

695 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SYCE3	SYCE2	Q6PIF2	983
SYCE3	SYCE1	Q8N0S2	973
SYCE3	TEX12	Q9BXU0	969
SYCE3	SYCP1	Q15431	938
SYCE3	SYCP3	Q8IZU3	902
SYCE3	C14orf39	Q8N1H7	822
SYCE3	SYCP2	Q9BX26	796
SYCE3	HORMAD1	Q86X24	732
SYCE3	MEIOB	Q8N635	646
SYCE3	STAG3	Q9UJ98	625
SYCE3	SPATA22	Q8NHS9	617
SYCE3	SMC1B	Q8NDV3	565
SYCE3	HORMAD2	Q8N7B1	539
SYCE3	REC8	O95072	537
SYCE3	SPO11	Q9Y5K1	530

IntAct

54 interactions, top by confidence:

A	B	Type	Score
SYCE3	HAUS1	psi-mi:“MI:0915”(physical association)	0.670
HAUS1	SYCE3	psi-mi:“MI:0915”(physical association)	0.670
BLOC1S6	SYCE3	psi-mi:“MI:0915”(physical association)	0.560
SYCE3	BLOC1S6	psi-mi:“MI:0915”(physical association)	0.560
SYCE3	PKN1	psi-mi:“MI:0915”(physical association)	0.560
SYCE3	KRT79	psi-mi:“MI:0915”(physical association)	0.560
SYCE3	SGF29	psi-mi:“MI:0915”(physical association)	0.560
SYCE3		psi-mi:“MI:0915”(physical association)	0.560
SYCE3	PRPS1	psi-mi:“MI:0915”(physical association)	0.560
SYCE3	WFS1	psi-mi:“MI:0915”(physical association)	0.560
KLF11	SYCE3	psi-mi:“MI:0915”(physical association)	0.560
NUP58	SYCE3	psi-mi:“MI:0915”(physical association)	0.560
SYCE3	HTT	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (99): SYCE3 (Two-hybrid), SYCE3 (Two-hybrid), CENPE (Affinity Capture-MS), MAP3K15 (Affinity Capture-MS), SCLT1 (Affinity Capture-MS), NIN (Affinity Capture-MS), SASS6 (Affinity Capture-MS), RUNX1T1 (Affinity Capture-MS), PRDM6 (Affinity Capture-MS), KIFC3 (Affinity Capture-MS), KIZ (Affinity Capture-MS), PEX11B (Affinity Capture-MS), FEM1B (Affinity Capture-MS), HAUS3 (Affinity Capture-MS), RB1CC1 (Affinity Capture-MS)

ESM2 similar proteins: A0R9B0, A1L190, A4GBY2, A4GCK2, A4GCL3, A4GCM4, A4IKB8, A4K148, A4U6V7, A4U7B1, A7GKT9, A7Z2G8, A9VSL6, B5KM66, B7H7K5, B7HTZ9, B7IVV9, B7JNA2, B9J2P7, C1EWA3, C3L658, C3PCM9, C5D5A9, O35041, P03504, P11619, P69259, P69260, P69266, P69267, P71080, P85939, Q18446, Q1K9P8, Q3ZC61, Q5L2X7, Q5RK03, Q5WFM7, Q63GH2, Q65MG3

Diamond homologs: A1L190, B5KM66

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SYCE3	“form complex”	Synaptonemal_complex	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	9
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

378 predictions. Top by Δscore:

Variant	Effect	Δscore
22:50551398:CTGCA:C	acceptor_gain	1.0000
22:50551399:TGCA:T	acceptor_gain	1.0000
22:50551400:GCACT:G	acceptor_loss	1.0000
22:50551402:ACTGC:A	acceptor_loss	1.0000
22:50551403:C:CC	acceptor_gain	1.0000
22:50551403:CTGC:C	acceptor_loss	1.0000
22:50551404:T:A	acceptor_loss	1.0000
22:50556292:CCTA:C	donor_loss	1.0000
22:50556293:CTA:C	donor_loss	1.0000
22:50556294:TACC:T	donor_loss	1.0000
22:50556295:A:AT	donor_loss	1.0000
22:50556296:C:CT	donor_loss	1.0000
22:50556413:A:AC	acceptor_gain	1.0000
22:50551400:GCA:G	acceptor_gain	0.9900
22:50551401:CA:C	acceptor_gain	0.9900
22:50551401:CAC:C	acceptor_gain	0.9900
22:50551409:C:CT	acceptor_gain	0.9900
22:50556401:TCCAT:T	acceptor_gain	0.9900
22:50556402:CCAT:C	acceptor_gain	0.9900
22:50556402:CCATC:C	acceptor_gain	0.9900
22:50556403:CAT:C	acceptor_gain	0.9900
22:50556403:CATC:C	acceptor_gain	0.9900
22:50556405:TCT:T	acceptor_loss	0.9900
22:50556406:C:CC	acceptor_gain	0.9900
22:50556406:C:T	acceptor_loss	0.9900
22:50556407:T:C	acceptor_loss	0.9900
22:50556411:C:CT	acceptor_gain	0.9900
22:50556412:A:T	acceptor_gain	0.9900
22:50556413:A:C	acceptor_gain	0.9900
22:50556416:C:CT	acceptor_gain	0.9900

AlphaMissense

591 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:50551397:C:G	A39P	0.985
22:50551319:C:G	A65P	0.982
22:50551363:C:G	R50P	0.982
22:50551314:G:C	F66L	0.981
22:50551314:G:T	F66L	0.981
22:50551316:A:G	F66L	0.981
22:50551385:C:G	A43P	0.981
22:50551384:G:T	A43D	0.979
22:50556308:T:A	E33V	0.977
22:50556344:A:G	L21P	0.977
22:50551364:G:T	R50S	0.976
22:50551378:T:A	D45V	0.976
22:50551386:C:A	M42I	0.974
22:50551386:C:G	M42I	0.974
22:50551386:C:T	M42I	0.974
22:50551327:A:G	L62P	0.972
22:50551302:C:A	K70N	0.965
22:50551302:C:G	K70N	0.965
22:50556323:A:G	L28P	0.965
22:50556332:A:G	L25S	0.965
22:50551382:A:C	Y44D	0.963
22:50551387:A:G	M42T	0.957
22:50551391:A:G	W41R	0.957
22:50551391:A:T	W41R	0.957
22:50551378:T:G	D45A	0.956
22:50551305:G:C	C69W	0.955
22:50551375:A:C	M46R	0.955
22:50556307:C:A	E33D	0.955
22:50556307:C:G	E33D	0.955
22:50551372:A:T	V47E	0.953

dbSNP variants (sampled 300 via entrez): RS1000018363 (22:50561473 A>G), RS1000521753 (22:50564667 T>C), RS1000559790 (22:50557128 T>C), RS1000775439 (22:50550655 G>A), RS1000909837 (22:50556835 A>G), RS1001288315 (22:50564112 A>C), RS1001646120 (22:50563142 T>G), RS1001695566 (22:50564325 A>G), RS1001698403 (22:50563503 C>A), RS1002496754 (22:50550890 C>A,T), RS1002579780 (22:50559915 A>C), RS1002624494 (22:50552330 ACT>A), RS1002635782 (22:50551631 T>TTCTGGATACACATG), RS1002640905 (22:50558480 C>G), RS1002784199 (22:50553144 G>A,C)

Disease associations

OMIM: gene MIM:615775 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST004602_305	Mean corpuscular volume	4.000000e-39
GCST004630_50	Mean corpuscular hemoglobin	6.000000e-25
GCST90002390_287	Mean corpuscular hemoglobin	4.000000e-12
GCST90002392_233	Mean corpuscular volume	9.000000e-19
GCST90002396_97	Mean reticulocyte volume	6.000000e-22
GCST90002397_615	Mean spheric corpuscular volume	2.000000e-26
GCST90002403_711	Red blood cell count	6.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004527	mean corpuscular hemoglobin
EFO:0010701	mean reticulocyte volume
EFO:0004305	erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
Vorinostat	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases abundance, increases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases methylation	1
Cadmium Chloride	increases abundance, increases expression	1
Particulate Matter	decreases methylation	1

Clinical trials (associated diseases)

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