| Name | KH domain containing 3-like, subcortical maternal complex member |
| Description | The protein encoded by this gene belongs to the KHDC1 family, members of which contain an atypical KH domain that may not bind RNA like canonical KH domains. This gene is specifically expressed in the oocytes, and recent studies suggest that it may function as a regulator of genomic imprinting in the oocyte. Mutations in this gene are associated with recurrent biparental complete hydatidiform mole. [provided by RefSeq, Dec 2011] |
| Summary |
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n KHDC3L, formerly known as C6orf221, is a maternal‐effect gene that plays a critical role during oogenesis and early embryonic development by ensuring the proper establishment and/or maintenance of maternal imprints. As a component of the subcortical maternal complex (SCMC), KHDC3L colocalizes with other SCMC proteins such as NLRP7 and exhibits a characteristic juxtanuclear/cortical distribution in oocytes and early embryos, suggesting that it is involved in spatially directing factors necessary for genomic imprinting and oocyte genome stability."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " \n Pathogenic variants in KHDC3L impair these functions, leading to aberrant imprint acquisition that manifests clinically as diploid, biparental hydatidiform moles and recurrent pregnancy loss (RPL)."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Genetic screening in affected families has revealed truncating mutations, with genotype–phenotype correlations indicating that homozygous deleterious variants are associated with early embryonic arrest and molar pregnancies, whereas heterozygous variants may present with less severe reproductive losses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Overall, these findings underscore the essential function of KHDC3L in coordinating epigenetic programming during oocyte maturation and early development. Disruption of KHDC3L function compromises genomic imprinting—a process fundamental to normal placental and embryonic development—thus predisposing affected women to severe reproductive disorders.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "David A Parry, Clare V Logan, Bruce E Hayward, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations causing familial biparental hydatidiform mole implicate c6orf221 as a possible regulator of genomic imprinting in the human oocyte."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2011.08.002"}], "href": "https://doi.org/10.1016/j.ajhg.2011.08.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21885028"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21885028"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ramesh Reddy, Elie Akoury, Ngoc Minh Phuong Nguyen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Report of four new patients with protein-truncating mutations in C6orf221/KHDC3L and colocalization with NLRP7."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Hum Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ejhg.2012.274"}], "href": "https://doi.org/10.1038/ejhg.2012.274"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23232697"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23232697"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "JianHua Qian, Ngoc Minh Phuong Nguyen, Maryam Rezaei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Biallelic PADI6 variants linking infertility, miscarriages, and hydatidiform moles."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Hum Genet (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41431-018-0141-3"}], "href": "https://doi.org/10.1038/s41431-018-0141-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29693651"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29693651"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Wei Zhao, Alanuer Muhetaer, TengFei Luo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Absence of KHDC3L mutations in Chinese patients with recurrent and sporadic hydatidiform moles."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cancergen.2013.09.003"}], "href": "https://doi.org/10.1016/j.cancergen.2013.09.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24215781"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24215781"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Nayeralsadat Fatemi, Pierre F Ray, Fariba Ramezanali, et al. "}, {"type": "b", "children": [{"type": "t", "text": "KH domain containing 3 like (KHDC3L) frame-shift mutation causes both recurrent pregnancy loss and hydatidiform mole."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Obstet Gynecol Reprod Biol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ejogrb.2021.02.006"}], "href": "https://doi.org/10.1016/j.ejogrb.2021.02.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33639414"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33639414"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Nayeralsadat Fatemi, Maryam Varkiani, Fariba Ramazanali, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A familial case of recurrent hydatidiform mole with p.Asp108Ilefs∗30 causing mutation in KHDC3L: A genetic and clinical report."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Taiwan J Obstet Gynecol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.tjog.2022.02.038"}], "href": "https://doi.org/10.1016/j.tjog.2022.02.038"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35361411"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35361411"}]}]}]}
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| Synonyms | ECAT1, C6ORF221, HYDM2 |
| Proteins | KHD3L_HUMAN |
| NCBI Gene ID | 154288 |
| API | |
| Download Associations | |
| Predicted Functions |
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| Co-expressed Genes |
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| Expression in Tissues and Cell Lines |
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KHDC3L has 2,452 functional associations with biological entities spanning 9 categories (molecular profile, organism, disease, phenotype or trait, functional term, phrase or reference, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 67 datasets.
Click the + buttons to view associations for KHDC3L from the datasets below.
If available, associations are ranked by standardized value
| Dataset | Summary | |
|---|---|---|
| Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles | tissues with high or low expression of KHDC3L gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset. | |
| Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of KHDC3L gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset. | |
| Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles | tissues with high or low expression of KHDC3L gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset. | |
| BioGPS Human Cell Type and Tissue Gene Expression Profiles | cell types and tissues with high or low expression of KHDC3L gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset. | |
| BioGPS Mouse Cell Type and Tissue Gene Expression Profiles | cell types and tissues with high or low expression of KHDC3L gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset. | |
| CCLE Cell Line Gene CNV Profiles | cell lines with high or low copy number of KHDC3L gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset. | |
| CCLE Cell Line Gene Expression Profiles | cell lines with high or low expression of KHDC3L gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset. | |
| CellMarker Gene-Cell Type Associations | cell types associated with KHDC3L gene from the CellMarker Gene-Cell Type Associations dataset. | |
| ChEA Transcription Factor Binding Site Profiles | transcription factor binding site profiles with transcription factor binding evidence at the promoter of KHDC3L gene from the CHEA Transcription Factor Binding Site Profiles dataset. | |
| ChEA Transcription Factor Targets | transcription factors binding the promoter of KHDC3L gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset. | |
| ClinVar Gene-Phenotype Associations | phenotypes associated with KHDC3L gene from the curated ClinVar Gene-Phenotype Associations dataset. | |
| CM4AI KOLF21J CRISPRi Gene Perturbation Atlas | gene perturbations changing expression of KHDC3L gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset. | |
| COMPARTMENTS Curated Protein Localization Evidence Scores 2025 | cellular components containing KHDC3L protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset. | |
| COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 | cellular components co-occuring with KHDC3L protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset. | |
| COSMIC Cell Line Gene CNV Profiles | cell lines with high or low copy number of KHDC3L gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset. | |
| DepMap CRISPR Gene Dependency | cell lines with fitness changed by KHDC3L gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset. | |
| DISEASES Text-mining Gene-Disease Association Evidence Scores | diseases co-occuring with KHDC3L gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset. | |
| DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 | diseases co-occuring with KHDC3L gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset. | |
| DisGeNET Gene-Disease Associations | diseases associated with KHDC3L gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset. | |
| ENCODE Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at KHDC3L gene from the ENCODE Histone Modification Site Profiles dataset. | |
| ENCODE Transcription Factor Binding Site Profiles | transcription factor binding site profiles with transcription factor binding evidence at the promoter of KHDC3L gene from the ENCODE Transcription Factor Binding Site Profiles dataset. | |
| ENCODE Transcription Factor Targets | transcription factors binding the promoter of KHDC3L gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset. | |
| ESCAPE Omics Signatures of Genes and Proteins for Stem Cells | PubMedIDs of publications reporting gene signatures containing KHDC3L from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset. | |
| GeneRIF Biological Term Annotations | biological terms co-occuring with KHDC3L gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset. | |
| GeneSigDB Published Gene Signatures | PubMedIDs of publications reporting gene signatures containing KHDC3L from the GeneSigDB Published Gene Signatures dataset. | |
| GEO Signatures of Differentially Expressed Genes for Gene Perturbations | gene perturbations changing expression of KHDC3L gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Kinase Perturbations | kinase perturbations changing expression of KHDC3L gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Small Molecules | small molecule perturbations changing expression of KHDC3L gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset. | |
| GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations | transcription factor perturbations changing expression of KHDC3L gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Viral Infections | virus perturbations changing expression of KHDC3L gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset. | |
| GO Biological Process Annotations 2023 | biological processes involving KHDC3L gene from the curated GO Biological Process Annotations 2023 dataset. | |
| GO Biological Process Annotations 2025 | biological processes involving KHDC3L gene from the curated GO Biological Process Annotations2025 dataset. | |
| GO Cellular Component Annotations 2023 | cellular components containing KHDC3L protein from the curated GO Cellular Component Annotations 2023 dataset. | |
| GO Cellular Component Annotations 2025 | cellular components containing KHDC3L protein from the curated GO Cellular Component Annotations 2025 dataset. | |
| GO Molecular Function Annotations 2015 | molecular functions performed by KHDC3L gene from the curated GO Molecular Function Annotations 2015 dataset. | |
| GTEx eQTL 2025 | SNPs regulating expression of KHDC3L gene from the GTEx eQTL 2025 dataset. | |
| GTEx Tissue Gene Expression Profiles | tissues with high or low expression of KHDC3L gene relative to other tissues from the GTEx Tissue Gene Expression Profiles dataset. | |
| GTEx Tissue Gene Expression Profiles 2023 | tissues with high or low expression of KHDC3L gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset. | |
| HPA Tissue Gene Expression Profiles | tissues with high or low expression of KHDC3L gene relative to other tissues from the HPA Tissue Gene Expression Profiles dataset. | |
| HPA Tissue Protein Expression Profiles | tissues with high or low expression of KHDC3L protein relative to other tissues from the HPA Tissue Protein Expression Profiles dataset. | |
| HPO Gene-Disease Associations | phenotypes associated with KHDC3L gene by mapping known disease genes to disease phenotypes from the HPO Gene-Disease Associations dataset. | |
| HuGE Navigator Gene-Phenotype Associations | phenotypes associated with KHDC3L gene by text-mining GWAS publications from the HuGE Navigator Gene-Phenotype Associations dataset. | |
| InterPro Predicted Protein Domain Annotations | protein domains predicted for KHDC3L protein from the InterPro Predicted Protein Domain Annotations dataset. | |
| JASPAR Predicted Human Transcription Factor Targets 2025 | transcription factors regulating expression of KHDC3L gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Human Transcription Factor Targets dataset. | |
| JASPAR Predicted Mouse Transcription Factor Targets 2025 | transcription factors regulating expression of KHDC3L gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Mouse Transcription Factor Targets 2025 dataset. | |
| JASPAR Predicted Transcription Factor Targets | transcription factors regulating expression of KHDC3L gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset. | |
| Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles | cell lines with high or low copy number of KHDC3L gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset. | |
| LOCATE Predicted Protein Localization Annotations | cellular components predicted to contain KHDC3L protein from the LOCATE Predicted Protein Localization Annotations dataset. | |
| MGI Mouse Phenotype Associations 2023 | phenotypes of transgenic mice caused by KHDC3L gene mutations from the MGI Mouse Phenotype Associations 2023 dataset. | |
| MiRTarBase microRNA Targets | microRNAs targeting KHDC3L gene in low- or high-throughput microRNA targeting studies from the MiRTarBase microRNA Targets dataset. | |
| MotifMap Predicted Transcription Factor Targets | transcription factors regulating expression of KHDC3L gene predicted using known transcription factor binding site motifs from the MotifMap Predicted Transcription Factor Targets dataset. | |
| MPO Gene-Phenotype Associations | phenotypes of transgenic mice caused by KHDC3L gene mutations from the MPO Gene-Phenotype Associations dataset. | |
| OMIM Gene-Disease Associations | phenotypes associated with KHDC3L gene from the curated OMIM Gene-Disease Associations dataset. | |
| PerturbAtlas Signatures of Differentially Expressed Genes for Mouse Gene Perturbations | gene perturbations changing expression of KHDC3L gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
| PFOCR Pathway Figure Associations 2024 | pathways involving KHDC3L protein from the Wikipathways PFOCR 2024 dataset. | |
| Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles | cell types and tissues with high or low DNA methylation of KHDC3L gene relative to other cell types and tissues from the Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles dataset. | |
| Roadmap Epigenomics Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at KHDC3L gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset. | |
| Rummagene Transcription Factor Associations 2026 | transcription factors regulating expression of KHDC3L gene from the Rummagene Transcription Factor Associations 2026 dataset. | |
| RummaGEO Drug Perturbation Signatures | drug perturbations changing expression of KHDC3L gene from the RummaGEO Drug Perturbation Signatures dataset. | |
| RummaGEO Gene Perturbation Signatures | gene perturbations changing expression of KHDC3L gene from the RummaGEO Gene Perturbation Signatures dataset. | |
| TargetScan Predicted Nonconserved microRNA Targets | microRNAs regulating expression of KHDC3L gene predicted using nonconserved miRNA seed sequences from the TargetScan Predicted Nonconserved microRNA Targets dataset. | |
| TCGA Signatures of Differentially Expressed Genes for Tumors | tissue samples with high or low expression of KHDC3L gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset. | |
| TISSUES Curated Tissue Protein Expression Evidence Scores | tissues with high expression of KHDC3L protein from the TISSUES Curated Tissue Protein Expression Evidence Scores dataset. | |
| TISSUES Curated Tissue Protein Expression Evidence Scores 2025 | tissues with high expression of KHDC3L protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset. | |
| TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 | tissues with high expression of KHDC3L protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 dataset. | |
| TISSUES Text-mining Tissue Protein Expression Evidence Scores | tissues co-occuring with KHDC3L protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores dataset. | |
| TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 | tissues co-occuring with KHDC3L protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset. | |
