SYCE1

Chr 10AR

synaptonemal complex central element protein 1

Also known as: C10orf94, CT76, POF12, SPGF15

NCBI Gene: 93426ENSG00000171772UniProt: Q8N0S2

The protein is a major component of the synaptonemal complex central element that forms between homologous chromosomes during meiotic prophase and is required for chromosome synapsis initiation and elongation. Mutations cause premature ovarian failure 12 and spermatogenic failure 15, affecting reproductive function in both males and females. Inheritance is autosomal recessive.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

Premature ovarian failure 12MIM #616947
AR
Spermatogenic failure 15MIM #616950
AR
0
Active trials
7
Pubs (1 yr)
107
P/LP submissions
1%
P/LP missense
0.96
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— SYCE1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
106 unique Pathogenic / Likely Pathogenic· 62 VUS of 256 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.96LOEUF
pLI 0.000
Z-score 1.69
OE 0.63 (0.42–0.96)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.66Z-score
OE missense 0.86 (0.76–0.98)
158 obs / 183.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.63 (0.42–0.96)
0≤0.351.4
Missense OE0.86 (0.76–0.98)
0≤0.61.4
Synonymous OE0.95
0≤1.21.6
LoF obs/exp: 15 / 23.9Missense obs/exp: 158 / 183.3Syn Z: 0.33
DN
0.75top 25%
GOF
0.75top 25%
LOF
0.2190th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

256 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic100
Likely Pathogenic6
VUS62
Likely Benign17
Benign64
100
Pathogenic
6
Likely Pathogenic
62
VUS
17
Likely Benign
64
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
1
94
0
100
Likely Pathogenic
0
0
6
0
6
VUS
0
41
21
0
62
Likely Benign
0
5
8
4
17
Benign
0
3
59
2
64
Total5501886249

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SYCE1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients