SYCE1

Chr 10AR

synaptonemal complex central element protein 1

Also known as: C10orf94, CT76, POF12, SPGF15

NCBI Gene: 93426 ENSG00000171772 UniProt: Q8N0S2 OMIM: 611486

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 0.962 OMIM phenotypes

Clinical Summary— SYCE1

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Gene-Disease Validity (ClinGen)

SYCE1-related gametogenic failure · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

11 unique Pathogenic / Likely Pathogenic· 42 VUS of 84 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 OE?0.63 (0.42–0.96)

0≤0.351.4

Missense OE?0.86 (0.76–0.98)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 15 / 23.9Missense obs/exp: 158 / 183.3Syn Z: 0.33

This gene — mechanism propensity

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

84 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10

Likely Pathogenic1

VUS42

Likely Benign15

Benign11

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	5	1	4	0	10
Likely Pathogenic	1	0	0	0	1
VUS	0	41	1	0	42
Likely Benign	0	5	6	4	15
Benign	0	3	6	2	11
Total	6	50	17	6	79

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

View in ClinVar →

96 pathogenic / likely-pathogenic (of 174) ClinVar copy-number / structural variants overlap SYCE1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →