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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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GMCL1
germ cell-less 1, spermatogenesis associated
Chromosome 2 · 2p13.3
NCBI Gene: 64395Ensembl: ENSG00000087338.6HGNC: HGNC:23843UniProt: Q53SE7
29PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingidentical protein bindingnucleusgerm cell developmentatrial fibrillationprotozoa infectious diseaseatrial flutterazoospermia
✦AI Summary

GMCL1 (germ cell-less 1, spermatogenesis associated) is a nuclear protein that functions as a negative regulator of cell cycle surveillance and DNA damage response pathways. The protein serves as a component of the CRL3GMCL1 ubiquitin ligase complex that targets 53BP1 for degradation during mitosis, thereby modulating p53 accumulation and cell cycle progression 1. GMCL1 physically interacts with 53BP1 and controls its stability, with depletion of GMCL1 leading to sensitization of cancer cells to paclitaxel in a p53-dependent manner 1. The protein also interacts with GAGE cancer-germline antigens and recruits them to the nuclear envelope through binding to LEM-domain proteins, suggesting a role in chr2 regulation 2. GMCL1 appears to have important functions in male fertility, as variants in this gene have been associated with male infertility and asthenozoospermia 34. Additionally, chr2 translocations involving GMCL1 can lead to aberrant heterochromatic foci formation and altered gene expression in B cell lymphoma, indicating its involvement in epigenetic regulation and potential tumor suppression 5. The gene shows tissue-specific expression patterns and has been implicated in various developmental processes including genital development 6.

Sources cited
1
GMCL1 functions as CRL3GMCL1 ubiquitin ligase targeting 53BP1 for degradation and modulates paclitaxel sensitivity
PMID: 41553759
2
GMCL1 interacts with GAGE proteins and recruits them to nuclear envelope through LEM-domain protein binding
PMID: 23029259
3
GMCL1 variants are associated with male infertility identified through exome sequencing
PMID: 36048845
4
GMCL1 is differentially expressed in asthenozoospermia spermatozoa
PMID: 30544396
5
GMCL1 chromosomal translocations form aberrant heterochromatic foci and affect gene expression in B cell lymphoma
PMID: 20432501
6
GMCL1 is involved in genital development and associated with hypospadias through DNA methylation studies
PMID: 32728162
Disease Associationsⓘ20
atrial fibrillationOpen Targets
0.44Moderate
protozoa infectious diseaseOpen Targets
0.25Weak
atrial flutterOpen Targets
0.13Weak
azoospermiaOpen Targets
0.10Weak
spermatogenic failure 78Open Targets
0.08Suggestive
partial chromosome Y deletionOpen Targets
0.08Suggestive
spermatogenic failure 65Open Targets
0.08Suggestive
deafness-infertility syndromeOpen Targets
0.08Suggestive
spermatogenic failure 54Open Targets
0.08Suggestive
spermatogenic failure 84Open Targets
0.08Suggestive
spermatogenic failure 93Open Targets
0.08Suggestive
spermatogenic failure 56Open Targets
0.08Suggestive
spermatogenic failure 92Open Targets
0.08Suggestive
spermatogenic failure 94Open Targets
0.08Suggestive
spermatogenic failure 51Open Targets
0.08Suggestive
spermatogenic failure, X-linked, 3Open Targets
0.08Suggestive
spermatogenic failure 39Open Targets
0.08Suggestive
spermatogenic failure 72Open Targets
0.08Suggestive
spermatogenic failure 91Open Targets
0.08Suggestive
spermatogenic failure 40Open Targets
0.08Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
GMCL2Shared pathway100%XAGE2Protein interaction72%DAZLShared pathway33%TCP11Shared pathway33%DND1Shared pathway25%RNF2Shared pathway25%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
45%
Ovary
33%
Liver
32%
Heart
28%
Lung
28%
Gene Interaction Network
Click a node to explore
GMCL1GMCL2XAGE2DAZLTCP11DND1RNF2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q53SE7
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.48LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.03 [0.73–1.48]
RankingsWhere GMCL1 stands among ~20K protein-coding genes
  • #12,155of 20,598
    Most Researched29
  • #15,056of 17,882
    Most Constrained (LOEUF)1.48
Genes detectedGMCL1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Novel potential causative genes in carotid paragangliomas.
PMID: 30967136
BMC Med Genet · 2019
1.00
2
GMCL1 controls 53BP1 stability and modulates taxane sensitivity.
PMID: 41553759
Elife · 2026
0.90
3
Altered mechanisms of genital development identified through integration of DNA methylation and genomic measures in hypospadias.
PMID: 32728162
Sci Rep · 2020
0.80
4
Epigenome-wide association analyses of active injection drug use.
PMID: 35395503
Drug Alcohol Depend · 2022
0.70
5
Exome sequencing and functional analyses revealed CETN1 variants leads to impaired cell division and male fertility.
PMID: 36048845
Hum Mol Genet · 2023
0.60