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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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KHDC3L
KH domain containing 3 like, subcortical maternal complex member
Chromosome 6 Β· 6q13
NCBI Gene: 154288Ensembl: ENSG00000203908.4HGNC: HGNC:33699UniProt: Q587J8
28PubMed Papers
21Diseases
0Drugs
4Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
regulation of protein localizationsubcortical maternal complexnucleusprotein bindingHydatidiform Molehydatidiform mole, recurrent, 2complete hydatidiform molegenetic disorder
✦AI Summary

KHDC3L is a subcortical maternal complex (SCMC) component essential for early embryonic development 1. As part of the SCMC, it contributes to cytoplasmic lattice formation, which stores maternal proteins critical for embryonic development 1. KHDC3L regulates multiple cellular processes: it ensures proper spindle assembly by localizing AURKA and PLK1, and positions MAD2L1 at kinetochores for checkpoint function 1. KHDC3L facilitates homologous recombination DNA repair by recruiting RAD51 to double-strand breaks and sustaining PARP1 activity; phosphorylation of Thr145 and Thr156 by ATM is critical for these functions 2. Additionally, it promotes replication fork restart by recruiting BLM and TRIM25 to stalled forks 1. KHDC3L dysfunction causes genomic instability in early embryonic cells, leading to recurrent pregnancy loss (RPL) 2. Biallelic mutations in KHDC3L are associated with recurrent diploid biparental hydatidiform moles through maternal imprinting defects 34. Clinically, KHDC3L variants are recognized genetic markers for oocyte quality defects, early embryo arrest, and reproductive failure, making it relevant for genetic counseling in infertility cases 15.

Sources cited
1
KHDC3L is one of 16 genes causing oocyte maturation abnormalities and early embryonic developmental defects; serves as molecular marker for oocyte/embryo quality
PMID: 33895934
2
KHDC3L mutations cause recurrent pregnancy loss through deficiency in PARP1 activation and homologous recombination repair; Thr145 and Thr156 phosphorylation by ATM are critical
PMID: 31609975
3
Biallelic KHDC3L variants cause recurrent diploid biparental moles through maternal imprinting defects
PMID: 31495354
4
KHDC3L mutations on chromosome 6q1 are associated with recurrent hydatidiform mole occurrences due to abnormal genomic imprinting
PMID: 39057130
5
KHDC3L is a SCMC gene screened in patients with recurrent embryo developmental problems after ICSI; variants of uncertain significance identified in infertile cohorts
PMID: 36931261
6
Biallelic mutations in KHDC3L predispose to diploid biparental moles and reproductive wastage
PMID: 23963444
Disease Associationsβ“˜21
Hydatidiform MoleOpen Targets
0.64Moderate
hydatidiform mole, recurrent, 2Open Targets
0.59Moderate
complete hydatidiform moleOpen Targets
0.37Weak
genetic disorderOpen Targets
0.19Weak
injuryOpen Targets
0.14Weak
benign neoplasm of eyeOpen Targets
0.06Suggestive
Posterior Leukoencephalopathy SyndromeOpen Targets
0.03Suggestive
myopiaOpen Targets
0.02Suggestive
refractive errorOpen Targets
0.02Suggestive
nephrotic syndromeOpen Targets
0.02Suggestive
Abnormality of refractionOpen Targets
0.02Suggestive
hypertensionOpen Targets
0.02Suggestive
ovarian dysfunctionOpen Targets
0.02Suggestive
response to xenobiotic stimulusOpen Targets
0.02Suggestive
ArthropathyOpen Targets
0.02Suggestive
Down syndromeOpen Targets
0.02Suggestive
nervous system diseaseOpen Targets
0.01Suggestive
Haim-Munk syndromeOpen Targets
0.01Suggestive
melanocytic nevusOpen Targets
0.01Suggestive
infertilityOpen Targets
0.01Suggestive
Hydatidiform mole, recurrent, 2UniProt
Pathogenic Variants4
NM_001017361.3(KHDC3L):c.334C>T (p.Gln112Ter)Likely pathogenic
Hydatidiform mole, recurrent, 2
β˜…β˜†β˜†β˜†2014β†’ Residue 112
NM_001017361.3(KHDC3L):c.322_325del (p.Asp108fs)Pathogenic
Hydatidiform mole, recurrent, 2|KHDC3L-related condition
β˜†β˜†β˜†β˜†2024β†’ Residue 108
NM_001017361.3(KHDC3L):c.299_302del (p.Ile100fs)Pathogenic
Hydatidiform mole, recurrent, 2
β˜†β˜†β˜†β˜†2013β†’ Residue 100
NM_001017361.3(KHDC3L):c.3G>T (p.Met1Ile)Pathogenic
Hydatidiform mole, recurrent, 2
β˜†β˜†β˜†β˜†2011β†’ Residue 1
View on ClinVar β†—
Related Genes
KHDC1Protein interaction99%OOEPProtein interaction84%FAUProtein interaction80%NLRP2Protein interaction67%NLRP5Protein interaction66%PADI6Protein interaction63%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
13%
Ovary
13%
Heart
0%
Liver
0%
Lung
0%
Gene Interaction Network
Click a node to explore
KHDC3LKHDC1OOEPFAUNLRP2NLRP5PADI6
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q587J8
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.96LoF Tolerant
pLIβ“˜
0.12Tolerant
Observed/Expected LoF0.49 [0.27–0.96]
RankingsWhere KHDC3L stands among ~20K protein-coding genes
  • #12,371of 20,598
    Most Researched28
  • #3,839of 5,498
    Most Pathogenic Variants4
  • #9,053of 17,882
    Most Constrained (LOEUF)0.96
Genes detectedKHDC3L
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Genetic factors as potential molecular markers of human oocyte and embryo quality.
PMID: 33895934
J Assist Reprod Genet Β· 2021
1.00
2
Gestational Trophoblastic Disease: Complete versus Partial Hydatidiform Moles.
PMID: 39057130
Diseases Β· 2024
0.90
3
KHDC3L mutation causes recurrent pregnancy loss by inducing genomic instability of human early embryonic cells.
PMID: 31609975
PLoS Biol Β· 2019
0.80
4
PMID: 40373180
0.70
5
Defects in meiosis I contribute to the genesis of androgenetic hydatidiform moles.
PMID: 39545410
J Clin Invest Β· 2024
0.60