SYCP3
protein-codingsynaptonemal complex protein 3
Gene summary
This gene encodes an essential structural component of the synaptonemal complex. This complex is involved in synapsis, recombination and segregation of meiotic chromosomes. Mutations in this gene are associated with azoospermia in males and susceptibility to pregnancy loss in females. Alternate splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, May 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~10.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0005047
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0010052
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Genitourinary; Obstetric
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SYCP3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001177949.2. 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 | 1 | 2 | 3 | |||
| missense | 38 | 3 | 41 | |||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 1 | 0 | 43 | 3 | 2 | 49 |
Highest pathogenic variant AF is 0.00006961456
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001171420.1 | 8 | MANE Select | |
| Ensembl | ENSP00000376655.1 | 8 | MANE Select | |
| RefSeq | NP_001171419.1 | 8 | Standard | |
| RefSeq | NP_710161.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Homologous recombination - Homo sapiens (human)
- Reproduction
- Meiotic synapsis
- Meiosis
- Cell Cycle
Biological Process
- male meiosis I
- spermatogenesis
- spermatid development
- spermatogenesis, exchange of chromosomal proteins
- cell division
Molecular Function
- DNA binding
Cellular Component
- chromosome, centromeric region
- synaptonemal complex
- lateral element
- nucleus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000392927
- Coding exons
- 8
- Length
- 10825
- Individuals with no LoFs
- 125715
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 31
- Defined
- 125746
- p
- 0.000123
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.536 | 102 | 118 | 0.861 | 0.00000573 | 1590 |
| Missense (PolyPhen) | 10 | 20.408 | 0.48999 | 325 | ||
| Synonymous | -0.187 | 38 | 36.6 | 1.04 | 0.00000183 | 370 |
| Loss of Function | 1.72 | 9 | 16.5 | 0.544 | 7.63e-7 | 199 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00021 | 0.00021 | rare |
| South Asian | 0.000066 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Component of the synaptonemal complexes (SCS), formed between homologous chromosomes during meiotic prophase. Required for centromere pairing during meiosis in male germ cells (By similarity). Required for normal meiosis during spermatogenesis and male fertility (PubMed:14643120). Plays a lesser role in female fertility. Required for efficient phosphorylation of HORMAD1 and HORMAD2 (By similarity). {ECO:0000250|UniProtKB:P70281, ECO:0000269|PubMed:14643120}.;
- Disease
- DISEASE: Spermatogenic failure 4 (SPGF4) [MIM:270960]: An infertility disorder characterized by azoospermia, a condition of having no sperm present in the ejaculate. Testicular histology shows arrest of spermatogenesis at the pachytene stage of primary spermatocytes. {ECO:0000269|PubMed:14643120}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Pregnancy loss, recurrent, 4 (RPRGL4) [MIM:270960]: A common complication of pregnancy, resulting in spontaneous abortion before the fetus has reached viability. The term includes all miscarriages from the time of conception until 24 weeks of gestation. Recurrent pregnancy loss is defined as 3 or more consecutive spontaneous abortions. {ECO:0000269|PubMed:19110213}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.142
Intolerance Scores
- LoFtool
- 0.374
- RVIS EVS
- -0.21
- RVIS percentile EVS
- 38.28
Essentials
- Essential (CRISPR)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.835
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |