SYCE3

Chr 22

synaptonemal complex central element protein 3

Also known as: C22orf41, THEG2

NCBI Gene: 644186 ENSG00000217442 UniProt: A1L190 OMIM: 615775

SYCE3 encodes a major component of the synaptonemal complex central element that is required for proper chromosome pairing and recombination during meiosis. Mutations cause male infertility due to impaired spermatogenesis and abnormal testis development, with autosomal recessive inheritance reported in the literature. The gene shows intermediate constraint against loss-of-function variants (pLI 0.60, LOEUF 1.02).

OMIM ResearchSummary from RefSeq, UniProt

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. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.02

Clinical Summary— SYCE3

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.60) — some intolerance to loss-of-function variants.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

1.02LOEUF

pLI 0.600

Z-score 1.57

OE 0.00 (0.00–1.02)

Moderately constrained

Highly tolerant — LoF variants common in population

Missense Constraint?

0.74Z-score

OE missense 0.71 (0.54–0.94)

36 obs / 50.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–1.02)

0≤0.351.4

Missense OE?0.71 (0.54–0.94)

0≤0.61.4

Synonymous OE?0.78

0≤1.21.6

LoF obs/exp: 0 / 2.9Missense obs/exp: 36 / 50.8Syn Z: 0.74

This gene — mechanism propensity

0.6840th %ile

GOF

0.79top 25%

LOF

0.3162th %ile

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

GOFprediction above median

DNprediction 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.