SYCE1

protein-coding

synaptonemal complex central element protein 1

Gene summary

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. [provided by RefSeq, Nov 2016]

Previous symbols:

C10orf94

MANE transcript

NM_001143764.3

Inheritance

AR, AD

ClinVar variants

P:7U:41B:14

Top phenotype

Premature ovarian failure 12

gnomAD constraint

pLI —, LoF o/e 0.63

Max pathogenic AF

—

Genomic locus

chr10:133,553,901-133,569,835

External References & Databases

Ensembl (ENSG00000171772)

Transcript & Mutation Effects

hg38 • Region Span ~15.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

premature ovarian failure 12STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014844

Submitter: Labcorp Genetics (formerly Invitae)

SYCE1-related gametogenic failureDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:1060214

Submitter: ClinGen

*SYCE1* was first reported in relation to autosomal recessive SYCE1-related gametogenic failure in 2014 (de Vries et al., PMID: 25062452). Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found no difference in molecular mechanism and inheritance pattern. Therefore, the following disease entities have been lumped into one disease entity: premature ovarian failure (OMIM: 616947) and spermatogenic failure (OMIM:616950). Five variants (missense, nonsense, frameshift) that have been reported in five probands in three publications (PMIDs: 25899990, 25062452, 40936058) are included in this curation. The mechanism of pathogenicity is believed to be biallelic loss of function (PMID: 25062452). This gene-disease relationship is also supported by animal models, expression studies, and in vitro functional assays (PMIDs: 32917591, 19247432, 33508233, 32402064, 32402064). In summary, there is definitive evidence supporting the relationship between *SYCE1* and SYCE1-related gametogenic failure. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Male Infertility GCEP on April 15, 2026 (SOP Version 12).

spermatogenic failure 15STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014847

Submitter: PanelApp Australia

premature ovarian failure 12STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014844

Submitter: PanelApp Australia

spermatogenic failure 15STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014847

Submitter: Labcorp Genetics (formerly Invitae)

male infertility with azoospermia or oligozoospermia due to single gene mutationSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0018393

Submitter: Orphanet

Clinical Genomic Database (CGD)

Premature ovarian failure 12AR

Manifestation: Endocrine; Genitourinary; Obstetric

Intervention: Endocrine; Obstetric

Rationale: The condition can include primary amenorrhea, and hormone therapy has been described as beneficial related to sexual development; Assistive reproductive technologies may be benefiical related to reproduction

Refs: 25062452; 25899990; 26203179

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SYCE1 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 51

not providedTotal: 12

Spermatogenic failure 15Total: 4

Premature ovarian failure 12Total: 4

SYCE1-related disorderTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001143764.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				4 clinvar	2 clinvar	6
missense	1 clinvar		40 clinvar	7 clinvar	1 clinvar	49
nonsense	1 clinvar		1 clinvar			2
start loss						0
frameshift	2 clinvar					2
splice donor/acceptor (+/-2bp)	2 clinvar	1 clinvar				3
Total	6	1	41	11	3	62

Highest pathogenic variant AF is 0.00020823159

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001143764.3	RefSeq	NP_001137236.1	13	MANE Select
ENST00000343131.7	Ensembl	ENSP00000341282.5	13	MANE Select
NM_001143763.2	RefSeq	NP_001137235.1	13	Standard
NM_130784.4	RefSeq	NP_570140.1	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

synaptonemal complex assembly
cell division

Molecular Function

protein binding

Cellular Component

synaptonemal complex
central element

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000343131
Coding exons: 13
Length: 15473
Individuals with no LoFs: 125628
Homozygous LoFs: 0
Heterozygous LoFs: 119
Defined: 125747
p: 0.000473

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.663	158	183	0.862	0.00000959	2289
Missense (PolyPhen)		38	51.757	0.73421		718
Synonymous	0.331	69	72.6	0.951	0.00000390	628
Loss of Function	1.69	15	23.9	0.626	0.00000117	271

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00038	0.00037	rare
Latino/Admixed American	0.00018	0.00017	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00038	0.00038	rare
Finnish	0.00083	0.00083	rare
European (Non-Finnish)	0.00059	0.00059	rare
South Asian	0.00033	0.00033	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: 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. {ECO:0000250|UniProtKB:Q9D495}.;
Disease: DISEASE: 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. {ECO:0000269|PubMed:25062452}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:25899990}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.0849

Intolerance Scores

LoFtool: 0.963
RVIS EVS: 1.37
RVIS percentile EVS: 94.52

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0459

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium