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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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C14orf39
chromosome 14 open reading frame 39
Chromosome 14 Β· 14q23.1
NCBI Gene: 317761Ensembl: ENSG00000179008.10HGNC: HGNC:19849UniProt: Q8N1H7
18PubMed Papers
22Diseases
0Drugs
9Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Swiss-Prot Reviewed
spermatogenic failure 52azoospermiapremature ovarian failure 18Microphthalmia - cataract
✦AI Summary

C14orf39 (also known as SIX6OS1) is a meiotic protein essential for proper chromosome 14 during meiotic recombination 1. The protein localizes to the central element of the synaptonemal complex (SC) and is required for SC assembly and chromosome 14 during meiosis 12. C14orf39 interacts with SYCE1 to form polycomplexes necessary for proper synapsis between homologous chr14 12. Pathogenic mutations in C14orf39 cause severe reproductive disorders including non-obstructive azoospermia in males and premature ovarian insufficiency (POI) in females 12. Homozygous mutations lead to complete or incomplete asynapsis between homologous chr14, resulting in meiotic arrest 1. Common genetic variants in C14orf39 are also associated with meiotic aneuploidy risk, highlighting its broader role in ensuring chr14 stability during meiosis 3. Clinical studies demonstrate that patients with meiotic gene defects, including C14orf39 mutations, have unsuccessful sperm retrieval rates, making genetic screening valuable for predicting treatment outcomes 4. The protein's conserved function across species underscores its fundamental importance in reproductive biology and meiotic fidelity.

Sources cited
1
C14orf39 localizes to synaptonemal complex, causes NOA and POI when mutated, and is required for chromosome synapsis
PMID: 33508233
2
C14orf39 variations affect protein stability and SC assembly, identified in POI and NOA patients
PMID: 34718620
3
Patients with meiotic gene defects including C14orf39 have unsuccessful sperm retrieval
PMID: 35172124
4
Common variants in C14orf39 are associated with meiotic aneuploidy risk
PMID: 40321295
5
C14orf39 is implicated in nonsyndromic POI and meiosis/DNA repair pathways
PMID: 34794894
6
C14orf39 variants identified in DOR/POI patients with meiotic pathway involvement
PMID: 40936058
7
C14orf39 variants identified in ovarian dysfunction patients through genetic screening
PMID: 36373164
Disease Associationsβ“˜22
spermatogenic failure 52Open Targets
0.63Moderate
azoospermiaOpen Targets
0.50Moderate
premature ovarian failure 18Open Targets
0.50Moderate
Microphthalmia - cataractOpen Targets
0.48Moderate
open-angle glaucomaOpen Targets
0.46Moderate
Developmental cataractOpen Targets
0.43Moderate
early-onset non-syndromic cataractOpen Targets
0.43Moderate
sclerocorneaOpen Targets
0.43Moderate
male infertility with azoospermia or oligozoospermia due to single gene mutationOpen Targets
0.38Weak
refractive errorOpen Targets
0.38Weak
mathematical abilityOpen Targets
0.37Weak
Abnormal urine sodium concentrationOpen Targets
0.34Weak
congenital cornea planaOpen Targets
0.34Weak
cornea planaOpen Targets
0.34Weak
MicrocorneaOpen Targets
0.34Weak
microphthalmiaOpen Targets
0.34Weak
NystagmusOpen Targets
0.34Weak
Abnormality of refractionOpen Targets
0.33Weak
Abnormality of the skeletal systemOpen Targets
0.29Weak
glaucomaOpen Targets
0.29Weak
Premature ovarian failure 18UniProt
Spermatogenic failure 52UniProt
Pathogenic Variants9
NM_174978.3(C14orf39):c.207_210del (p.Ser69fs)Likely pathogenic
Spermatogenic failure 52;Premature ovarian failure 18
β˜…β˜†β˜†β˜†2025β†’ Residue 69
NM_174978.3(C14orf39):c.139_142del (p.Thr47fs)Pathogenic
Spermatogenic failure 52
β˜…β˜†β˜†β˜†2024β†’ Residue 47
NM_174978.3(C14orf39):c.508C>T (p.Arg170Ter)Pathogenic
Premature ovarian failure 18
β˜†β˜†β˜†β˜†2026β†’ Residue 170
NM_174978.3(C14orf39):c.135_136del (p.Lys45fs)Pathogenic
Spermatogenic failure 52
β˜†β˜†β˜†β˜†2026β†’ Residue 45
NM_174978.3(C14orf39):c.1349del (p.Pro450fs)Pathogenic
Premature ovarian failure 18
β˜†β˜†β˜†β˜†2026β†’ Residue 450
NM_174978.3(C14orf39):c.1154_1157del (p.Val385fs)Pathogenic
Premature ovarian failure 18
β˜†β˜†β˜†β˜†2026β†’ Residue 385
NM_174978.3(C14orf39):c.204_205del (p.His68fs)Pathogenic
Spermatogenic failure 52|Premature ovarian failure 18|Non-obstructive azoospermia|Azoospermia
β˜†β˜†β˜†β˜†2021β†’ Residue 68
NM_174978.3(C14orf39):c.1180-3C>GPathogenic
Spermatogenic failure 52|Non-obstructive azoospermia
β˜†β˜†β˜†β˜†2021
NM_174978.3(C14orf39):c.958G>T (p.Glu320Ter)Pathogenic
Spermatogenic failure 52|Non-obstructive azoospermia
β˜†β˜†β˜†β˜†2021β†’ Residue 320
View on ClinVar β†—
Related Genes
SYCE3Protein interaction99%SYCP1Protein interaction87%TEX12Protein interaction87%SYCE2Protein interaction87%SYCE1Protein interaction70%SMC1BCo-mentioned in literature30%
Tissue Expression6 tissues
Ovary
100%
Brain
12%
Lung
3%
Bone Marrow
0%
Heart
0%
Liver
0%
Gene Interaction Network
Click a node to explore
C14orf39SYCE3SYCP1TEX12SYCE2SYCE1SMC1B
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q8N1H7
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.31LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.89 [0.62–1.31]
RankingsWhere C14orf39 stands among ~20K protein-coding genes
  • #14,647of 20,598
    Most Researched18
  • #3,002of 5,498
    Most Pathogenic Variants9
  • #13,747of 17,882
    Most Constrained (LOEUF)1.31
Genes detectedC14orf39
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Genetics of ovarian insufficiency and defects of folliculogenesis.
PMID: 34794894
Best Pract Res Clin Endocrinol Metab Β· 2022
1.00
2
Whole-exome sequencing improves the diagnosis and care of men with non-obstructive azoospermia.
PMID: 35172124
Am J Hum Genet Β· 2022
0.90
3
Common variation in meiosis genes shapes human recombination and aneuploidy.
PMID: 41565805
Nature Β· 2026
0.80
4
Variations of C14ORF39 and SYCE1 Identified in Idiopathic Premature Ovarian Insufficiency and Nonobstructive Azoospermia.
PMID: 34718620
J Clin Endocrinol Metab Β· 2022
0.70
5
Genetic variants in diminished ovarian reserve and premature ovarian insufficiency: implications for assisted reproductive outcomes.
PMID: 40936058
J Assist Reprod Genet Β· 2025
0.60