KDM4C (lysine demethylase 4C)

Gene

• Entrez ID: 23081
• Gene name: Lysine demethylase 4C
• Gene symbol: KDM4C
• Synonyms (NCBI Gene): GASC1, JHDM3C, JMJD2C, TDRD14C
• Chromosome: 9
• Chromosome location: 9p24.1
• Summary: This gene is a member of the Jumonji domain 2 (JMJD2) family. The encoded protein is a trimethylation-specific demethylase, and converts specific trimethylated histone residues to the dimethylated form. This enzymatic action regulates gene expression and

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT016783	hsa-miR-335-5p	Microarray	18185580
MIRT440401	hsa-miR-432-5p	HITS-CLIP	24374217
MIRT440400	hsa-miR-409-3p	HITS-CLIP	24374217
MIRT440401	hsa-miR-432-5p	HITS-CLIP	24374217
MIRT440400	hsa-miR-409-3p	HITS-CLIP	24374217
MIRT1084581	hsa-miR-3689a-5p	CLIP-seq
MIRT1084582	hsa-miR-3689b	CLIP-seq
MIRT1084583	hsa-miR-3689e	CLIP-seq
MIRT1084584	hsa-miR-3689f	CLIP-seq
MIRT1084585	hsa-miR-4291	CLIP-seq
MIRT1084586	hsa-miR-545	CLIP-seq
MIRT1084587	hsa-miR-556-5p	CLIP-seq
MIRT737734	hsa-miR-4765	CLIP-seq
MIRT737735	hsa-miR-5096	CLIP-seq
MIRT1084588	hsa-miR-1178	CLIP-seq
MIRT1084589	hsa-miR-1324	CLIP-seq
MIRT1084590	hsa-miR-216a	CLIP-seq
MIRT1084591	hsa-miR-335	CLIP-seq
MIRT1084592	hsa-miR-3613-3p	CLIP-seq
MIRT1084593	hsa-miR-3686	CLIP-seq
MIRT1084594	hsa-miR-4272	CLIP-seq
MIRT1084595	hsa-miR-4277	CLIP-seq
MIRT1084596	hsa-miR-4282	CLIP-seq
MIRT1084597	hsa-miR-4457	CLIP-seq
MIRT1084598	hsa-miR-4495	CLIP-seq
MIRT1084599	hsa-miR-451b	CLIP-seq
MIRT1084600	hsa-miR-4696	CLIP-seq
MIRT1084601	hsa-miR-4719	CLIP-seq
MIRT1084602	hsa-miR-4753-5p	CLIP-seq
MIRT1084603	hsa-miR-513a-3p	CLIP-seq
MIRT1084604	hsa-miR-513b	CLIP-seq
MIRT1084605	hsa-miR-513c	CLIP-seq
MIRT1084606	hsa-miR-514b-5p	CLIP-seq
MIRT1084607	hsa-miR-548n	CLIP-seq
MIRT1084608	hsa-miR-548t	CLIP-seq
MIRT1084609	hsa-miR-579	CLIP-seq
MIRT1084610	hsa-miR-599	CLIP-seq
MIRT1084611	hsa-miR-602	CLIP-seq
MIRT1084612	hsa-miR-624	CLIP-seq
MIRT1084613	hsa-miR-767-3p	CLIP-seq
MIRT737734	hsa-miR-4765	CLIP-seq
MIRT737735	hsa-miR-5096	CLIP-seq
MIRT2442292	hsa-miR-4268	CLIP-seq
MIRT2442293	hsa-miR-4448	CLIP-seq
MIRT2442294	hsa-miR-4694-5p	CLIP-seq
MIRT2452337	hsa-miR-1236	CLIP-seq
MIRT2452338	hsa-miR-4768-5p	CLIP-seq
MIRT2452339	hsa-miR-942	CLIP-seq
MIRT2555923	hsa-miR-1281	CLIP-seq
MIRT2555924	hsa-miR-3144-5p	CLIP-seq
MIRT2555925	hsa-miR-3918	CLIP-seq
MIRT1084597	hsa-miR-4457	CLIP-seq
MIRT2555923	hsa-miR-1281	CLIP-seq
MIRT2555924	hsa-miR-3144-5p	CLIP-seq
MIRT2555925	hsa-miR-3918	CLIP-seq
MIRT1084597	hsa-miR-4457	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000785	Component	Chromatin	IBA
GO:0000785	Component	Chromatin	IDA	17277772
GO:0001825	Process	Blastocyst formation	IEA
GO:0003713	Function	Transcription coactivator activity	IGI	17277772
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IEA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005721	Component	Pericentric heterochromatin	IEA
GO:0006325	Process	Chromatin organization	IEA
GO:0006338	Process	Chromatin remodeling	IBA
GO:0008270	Function	Zinc ion binding	IDA	21914792
GO:0008270	Function	Zinc ion binding	IEA
GO:0008284	Process	Positive regulation of cell population proliferation	IMP	17277772
GO:0010468	Process	Regulation of gene expression	IBA
GO:0010468	Process	Regulation of gene expression	IEA
GO:0016491	Function	Oxidoreductase activity	IEA
GO:0019827	Process	Stem cell population maintenance	IEA
GO:0019899	Function	Enzyme binding	IEA
GO:0019899	Function	Enzyme binding	IPI	17277772
GO:0030521	Process	Androgen receptor signaling pathway	IDA	17277772
GO:0032452	Function	Histone demethylase activity	EXP	18066052
GO:0032452	Function	Histone demethylase activity	IEA
GO:0032452	Function	Histone demethylase activity	TAS
GO:0032454	Function	Histone H3K9 demethylase activity	IBA
GO:0032454	Function	Histone H3K9 demethylase activity	IDA	18066052
GO:0032454	Function	Histone H3K9 demethylase activity	IEA
GO:0032454	Function	Histone H3K9 demethylase activity	IMP	28262558
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	17277772
GO:0046872	Function	Metal ion binding	IEA
GO:0050681	Function	Nuclear androgen receptor binding	IEA
GO:0050681	Function	Nuclear androgen receptor binding	IPI	17277772
GO:0051213	Function	Dioxygenase activity	IEA
GO:0051864	Function	Histone H3K36 demethylase activity	IBA
GO:0051864	Function	Histone H3K36 demethylase activity	IDA	21914792
GO:0051864	Function	Histone H3K36 demethylase activity	IEA
GO:0060765	Process	Regulation of androgen receptor signaling pathway	TAS
GO:0140684	Function	Histone H3K9me2/H3K9me3 demethylase activity	IDA	21914792
GO:0140684	Function	Histone H3K9me2/H3K9me3 demethylase activity	IEA
GO:0140684	Function	Histone H3K9me2/H3K9me3 demethylase activity	IMP	17277772
GO:2000736	Process	Regulation of stem cell differentiation	IEA

Other IDs

• MIM: 605469
• HGNC: 17071
• e!Ensembl: ENSG00000107077

Protein

• UniProt ID: Q9H3R0
• Protein name: Lysine-specific demethylase 4C (EC 1.14.11.66) (Gene amplified in squamous cell carcinoma 1 protein) (GASC-1 protein) (JmjC domain-containing histone demethylation protein 3C) (Jumonji domain-containing protein 2C) ([histone H3]-trimethyl-L-lysine(9) deme
• Protein function: Histone demethylase that specifically demethylates 'Lys-9' and 'Lys-36' residues of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-4', H3 'Lys-27' nor H4 'Lys-20'. Demethylates trimethylated H3 '
• PDB: 2XDP, 2XML, 4XDO, 4XDP, 5FJH, 5FJK, 5KR7
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF02375	JmjN	17 → 51	jmjN domain	Family
  PF02373	JmjC	177 → 293	JmjC domain, hydroxylase	Domain
  PF13831	PHD_2	712 → 747		Family
  PF13832	zf-HC5HC2H_2	753 → 864		Domain
  PF18104	Tudor_2	882 → 916	Jumonji domain-containing protein 2A Tudor domain	Domain
  PF18104	Tudor_2	940 → 974	Jumonji domain-containing protein 2A Tudor domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Overexpressed in several esophageal squamous cell carcinomas (ESCs). {ECO:0000269|PubMed:10987278}.
• Sequence:

  MEVAEVESPLNPSCKIMTFRPSMEEFREFNKYLAYMESKGAHRAGLAKVIPPKEWKPRQC
  YDDIDNLLIPAPIQQMVTGQSGLFTQYNIQKKAMTVKEFRQLANSGKYCTPRYLDYEDLE
  RKYWKNLTFVAPIYGADINGSIYDEGVDEWNIARLNTVLDVVEEECGISIEGVNTPYLYF
  GMWKTTFAWHTEDMDLYSINYLHFGEPKSWYAIPPEHGKRLERLAQGFFPSSSQGCDAFL
  RHKMTLISPSVLKKYGIPFDKITQEAGEFMITFPYGYHAGFNHGFNCAESTNFATVRWID
  YGKVAKLCTCRKDMVKISMDIFVRKFQPDRYQLWKQGKDIYTIDHTKPTPASTPEVKAWL
  QRRRKVRKASRSFQCARSTSKRPKADEEEEVSDEVDGAEVPNPDSVTDDLKVSEKSEAAV
  KLRNTEASSEEESSASRMQVEQNLSDHIKLSGNSCLSTSVTEDIKTEDDKAYAYRSVPSI
  SSEADDSIPLSSGYEKPEKSDPSELSWPKSPESCSSVAESNGVLTEGEESDVESHGNGLE
  PGEIPAVPSGERNSFKVPSIAEGENKTSKSWRHPLSRPPARSPMTLVKQQAPSDEELPEV
  LSIEEEVEETESWAKPLIHLWQTKSPNFAAEQEYNATVARMKPHCAICTLLMPYHKPDSS
  NEENDARWETKLDEVVTSEGKTKPLIPEMCFIYSEENIEYSPPNAFLEEDGTSLLISCAK
  CCVRVHASCYGIPSHEICDGWLCARCKRNAWTAECCLCNLRGGALKQTKNNKWAHVMCAV
  AVPEVRFTNVPERTQIDVGRIPLQRLKLKCIFCRHRVKRVSGACIQCSYGRCPASFHVTC
  AHAAGVLMEPDDWPYVVNITCFRHKVNPNVKSKACEKVISVGQTVITKHRNTRYYSCRVM
  AVTSQTFYEVMFDDGSFSRDTFPEDIVSRDCLKLGPPAEGEVVQVKWPDGKLYGAKYFGS
  NIAHMYQVEFEDGSQIAMKREDIYTLDEELPKRVKARFSTASDMRFEDTFYGADIIQGER
  KRQRVLSSRFKNEYVADPVYRTFLKSSFQKKCQKRQ

• Sequence length: 1056

Pathways

Reactome:

HDMs demethylate histones
Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ASTHMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISTIC DISORDER	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BIPOLAR DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BREAST CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BREAST CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHOLECYSTITIS, ACUTE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHOLELITHIASIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Enchondromatosis	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
KDM4C-related disorder	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Maffucci syndrome	Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Malignant tumor of esophagus	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MEDULLOBLASTOMA	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MELANOMA	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MELANOMA, EXPERIMENTAL	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MENTAL OR BEHAVIOURAL DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OBESITY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PSYCHIATRIC DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
RESTLESS LEGS SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCOLIOSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SYSTEMIC LUPUS ERYTHEMATOSUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TREATMENT-RESISTANT HYPERTENSION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
VASCULITIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acute leukemia	Leukemia	BEFREE	26766589		★☆☆☆☆ Found in Text Mining only
Adult Hodgkin Lymphoma	Hodgkin Lymphoma	BEFREE	21156283		★☆☆☆☆ Found in Text Mining only
Adult Medulloblastoma	Medulloblastoma	CTD_human_DG	19270706		★☆☆☆☆ Found in Text Mining only
ATRIAL SEPTAL DEFECT 1	Atrial Septal Defect	BEFREE	20410850		★☆☆☆☆ Found in Text Mining only
Atrial Septal Defects	Atrial Septal Defect	BEFREE	20410850		★☆☆☆☆ Found in Text Mining only
Autism Spectrum Disorder	Autism	Pubtator	33279929	Associate	★☆☆☆☆ Found in Text Mining only
Autism Spectrum Disorders	Autism Spectrum Disorder	BEFREE	20410850		★☆☆☆☆ Found in Text Mining only
Autistic Disorder	Autism	BEFREE	20410850		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Benign Prostatic Hyperplasia	Benign Prostatic Hyperplasia	BEFREE	20127736		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	23129632, 24952432, 25220908, 29207681, 30083054		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Breast Neoplasms	Breast neoplasm	Pubtator	21666724, 23148692, 24952432, 25220908, 27223606	Associate	★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	27223606, 31888886	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma	Carcinoma	BEFREE	17277772, 29207681		★☆☆☆☆ Found in Text Mining only
Carcinoma of lung	Lung carcinoma	BEFREE	28236704		★☆☆☆☆ Found in Text Mining only
Carcinoma Renal Cell	Renal cell carcinoma	Pubtator	22483639, 25220908, 31575031	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Squamous Cell	Squamous cell carcinoma	Pubtator	11346465, 21666724, 24394434	Associate	★☆☆☆☆ Found in Text Mining only
Childhood Medulloblastoma	Medulloblastoma	CTD_human_DG	19270706		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	23698634, 31665047		★☆☆☆☆ Found in Text Mining only
Conventional (Clear Cell) Renal Cell Carcinoma	Renal Carcinoma	BEFREE	22483639		★☆☆☆☆ Found in Text Mining only
Desmoplastic Medulloblastoma	Medulloblastoma	BEFREE	16400626		★☆☆☆☆ Found in Text Mining only
Desmoplastic Medulloblastoma	Medulloblastoma	CTD_human_DG	19270706		★☆☆☆☆ Found in Text Mining only
Esophageal Neoplasms	Esophageal neoplasm	Pubtator	19339270	Associate	★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	Pubtator	31888886	Stimulate	★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	Pubtator	31888886	Associate	★☆☆☆☆ Found in Text Mining only
Hodgkin Disease	Hodgkin Disease	BEFREE	21156283		★☆☆☆☆ Found in Text Mining only
Hodgkin Disease	Hodgkin disease	Pubtator	21156283, 35522148	Associate	★☆☆☆☆ Found in Text Mining only
Infertility Male	Male infertility	Pubtator	31103287	Associate	★☆☆☆☆ Found in Text Mining only
Latent Autoimmune Diabetes in Adults	Autoimmune Diabetes	BEFREE	28396876		★☆☆☆☆ Found in Text Mining only
Latent Autoimmune Diabetes in Adults	Latent autoimmune diabetes in adults	Pubtator	28396876	Associate	★☆☆☆☆ Found in Text Mining only
leukemia	Leukemia	BEFREE	25220908, 30426231		★☆☆☆☆ Found in Text Mining only
Leukemia	Leukemia	Pubtator	25220908	Associate	★☆☆☆☆ Found in Text Mining only
Leukemia, Myelocytic, Acute	Leukemia	BEFREE	26766589		★☆☆☆☆ Found in Text Mining only
Lymphoma	Lymphoma	BEFREE	21156283		★☆☆☆☆ Found in Text Mining only
Lymphoma	Lymphoma	Pubtator	21156283, 26850007, 35522148	Associate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	23129632, 24952432, 25220908, 29207681, 30083054		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of lung	Lung Cancer	BEFREE	28236704		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of pancreas	Pancreatic cancer	BEFREE	30537731		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	BEFREE	20127736, 22867098, 31766290		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	25220908, 25636512		★☆☆☆☆ Found in Text Mining only
Mammary Neoplasms	Mammary Neoplasms	BEFREE	23129632		★☆☆☆☆ Found in Text Mining only
Medulloblastoma	Medulloblastoma	CTD_human_DG	19270706		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Medullomyoblastoma	Medullomyoblastoma	CTD_human_DG	19270706		★☆☆☆☆ Found in Text Mining only
melanoma	Melanoma	CTD_human_DG	29438700		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Melanoma	Pubtator	38252669	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanotic medulloblastoma	Medulloblastoma	CTD_human_DG	19270706		★☆☆☆☆ Found in Text Mining only
Mucosa-Associated Lymphoid Tissue Lymphoma	Mucosa-associated lymphoma	LHGDN	18927281		★☆☆☆☆ Found in Text Mining only
Multiple Myeloma	Multiple myeloma	Pubtator	33469678	Stimulate	★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	17277772, 23644528, 24952432, 28236704, 31665047, 31766290		★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	BEFREE	29077881		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Obsessive-Compulsive Disorder	Obsessive-Compulsive Disorder	BEFREE	20410850		★☆☆☆☆ Found in Text Mining only
Osteosarcoma	Osteosarcoma	BEFREE	25636512, 29207681		★☆☆☆☆ Found in Text Mining only
Ovarian Neoplasms	Ovarian neoplasm	Pubtator	26864203, 36804120	Associate	★☆☆☆☆ Found in Text Mining only
Pancreatic carcinoma	Pancreatic carcinoma	BEFREE	30537731		★☆☆☆☆ Found in Text Mining only
Papillary Renal Cell Carcinoma	Papillary Renal Carcinoma	BEFREE	31575031		★☆☆☆☆ Found in Text Mining only
Prostate carcinoma	Prostate cancer	BEFREE	20127736, 22867098, 31766290		★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	25220908	Associate	★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic Neoplasms	BEFREE	31766290		★☆☆☆☆ Found in Text Mining only
Renal Cell Carcinoma	Renal Carcinoma	BEFREE	22483639		★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	GWASCAT_DG	28991256, 30285260		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Schizophrenia	Schizophrenia	Pubtator	33279929	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Squamous cell carcinoma	Carcinoma	BEFREE	24394434		★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma of esophagus	Esophagus Neoplasm	BEFREE	11346465, 15138608, 15805246, 25220908		★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	37848946	Associate	★☆☆☆☆ Found in Text Mining only
T-Cell Lymphoma	T-Cell Lymphoma	CTD_human_DG	29438700		★☆☆☆☆ Found in Text Mining only
Triple Negative Breast Neoplasms	Triple Negative Breast Neoplasms	BEFREE	30083054		★☆☆☆☆ Found in Text Mining only