KDM5C

lysine demethylase 5C, the group of Lysine demethylases|MicroRNA protein coding host genes|AT-rich interaction domain containing|PHD finger proteins

Basic information

Region (hg38): X:53176277-53225422

Previous symbols: [ "SMCX", "JARID1C", "MRX13" ]

Links

ENSG00000126012 ∙ NCBI:8242 ∙ OMIM:314690 ∙ HGNC:11114 ∙ Uniprot:P41229 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• syndromic X-linked intellectual disability Claes-Jensen type (Definitive), mode of inheritance: XLR
• syndromic X-linked intellectual disability Claes-Jensen type (Supportive), mode of inheritance: XL
• syndromic X-linked intellectual disability Claes-Jensen type (Definitive), mode of inheritance: XL
• syndromic X-linked intellectual disability Claes-Jensen type (Strong), mode of inheritance: XL
• X-linked syndromic intellectual disability (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, X-linked, syndromic, Claes-Jensen type	XL	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Genitourinary; Musculoskeletal; Neurologic	10982473; 15586325; 16538222; 18697827; 18203167; 19826449; 21575681; 22326837; 22611640

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KDM5C gene.

• not provided (35 variants)
• Syndromic X-linked intellectual disability Claes-Jensen type (24 variants)
• Spastic paraplegia (16 variants)
• Inborn genetic diseases (10 variants)
• Intellectual disability (4 variants)
• Rare genetic intellectual disability (1 variants)
• Developmental disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KDM5C gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	138	25	167
missense	7	23	211	25	13	279
nonsense	32	5	1			38
start loss		1				1
frameshift	33	8				41
inframe indel			8			8
splice donor/acceptor (+/-2bp)	3	13	1			17
splice region			13	11	3	27
non coding			8	63	30	101
Total	75	50	233	226	68

Highest pathogenic variant AF is 0.00000898

Variants in KDM5C

This is a list of pathogenic ClinVar variants found in the KDM5C region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
X-53191607-T-C			Uncertain significance (Oct 01, 2023)
X-53192476-G-A			Likely benign (Dec 17, 2018)
X-53192587-C-T			Likely benign (Oct 10, 2019)
X-53192606-G-T			Likely benign (Jul 27, 2018)
X-53192769-G-T			Uncertain significance (Feb 01, 2017)
X-53192774-C-G			Likely benign (Oct 01, 2024)
X-53192818-A-G		not specified	Uncertain significance (Sep 27, 2024)
X-53192834-A-T		KDM5C-related disorder	Likely benign (Feb 08, 2024)
X-53192835-G-C		not specified	not provided (Sep 19, 2013)
X-53192837-G-C			Uncertain significance (Feb 01, 2019)
X-53192837-G-T		KDM5C-related disorder	Likely benign (Jul 01, 2023)
X-53192838-G-A		Syndromic X-linked intellectual disability Claes-Jensen type	Uncertain significance (Apr 27, 2019)
X-53192843-C-G		KDM5C-related disorder • Inborn genetic diseases	Conflicting classifications of pathogenicity (Dec 20, 2023)
X-53192843-C-T			Likely benign (Jan 21, 2021)
X-53192858-GCCACCCCCCTACCCGC-G			Benign (Dec 05, 2018)
X-53192861-A-AC			Benign (Jul 03, 2018)
X-53192868-T-C			Benign (Mar 28, 2020)
X-53192869-A-C			Benign (Mar 29, 2020)
X-53192873-G-C			Likely benign (Aug 17, 2018)
X-53192881-C-T			Likely benign (Dec 17, 2018)
X-53192924-C-T			Benign (Apr 09, 2021)
X-53192975-G-C			Uncertain significance (May 28, 2019)
X-53192975-G-T			Likely benign (Oct 01, 2024)
X-53192976-T-C			Uncertain significance (Dec 07, 2017)
X-53192985-C-T		Spastic paraplegia • Inborn genetic diseases	Likely benign (Aug 04, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KDM5C	protein_coding	protein_coding	ENST00000375401	26	34102

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000147	125742	1	4	125747	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	5.15	293	667	0.439	0.0000572	10067
Missense in Polyphen		43	263.2	0.16337		4170
Synonymous	-0.582	272	260	1.05	0.0000201	3210
Loss of Function	6.38	4	55.1	0.0726	0.00000433	846

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000760	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000128	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.000158	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Histone demethylase that specifically demethylates 'Lys- 4' of histone H3, thereby playing a central role in histone code (PubMed:28262558). Does not demethylate histone H3 'Lys-9', H3 'Lys-27', H3 'Lys-36', H3 'Lys-79' or H4 'Lys-20'. Demethylates trimethylated and dimethylated but not monomethylated H3 'Lys-4'. Participates in transcriptional repression of neuronal genes by recruiting histone deacetylases and REST at neuron-restrictive silencer elements. Represses the CLOCK-ARNTL/BMAL1 heterodimer- mediated transcriptional activation of the core clock component PER2 (By similarity). {ECO:0000250|UniProtKB:P41230, ECO:0000269|PubMed:17320160, ECO:0000269|PubMed:17320161, ECO:0000269|PubMed:17468742, ECO:0000269|PubMed:26645689, ECO:0000269|PubMed:28262558}.
• Disease: DISEASE: Mental retardation, X-linked, syndromic, Claes-Jensen type (MRXSCJ) [MIM:300534]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRXSCJ patients manifest mental retardation associated with variable features such as slowly progressive spastic paraplegia, seizures, facial dysmorphism. {ECO:0000269|PubMed:15586325, ECO:0000269|PubMed:16538222, ECO:0000269|PubMed:16541399, ECO:0000269|PubMed:17320160, ECO:0000269|PubMed:17468742, ECO:0000269|PubMed:23356856, ECO:0000269|PubMed:25666439}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Pathways in clear cell renal cell carcinoma;HDMs demethylate histones;Chromatin modifying enzymes;Chromatin organization (Consensus)

Recessive Scores

• pRec: 0.193

Intolerance Scores

• loftool: 0.0636
• rvis_EVS: -1.51
• rvis_percentile_EVS: 3.5

Haploinsufficiency Scores

• pHI: 0.235
• hipred: Y
• hipred_score: 0.839
• ghis: 0.527

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.730

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Kdm5c
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: kdm5c
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: curved ventral

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;chromatin remodeling;histone H3-K4 demethylation;histone H3-K4 demethylation, trimethyl-H3-K4-specific;negative regulation of transcription, DNA-templated;rhythmic process;oxidation-reduction process
• Cellular component: nucleus;nucleoplasm;cytosol;histone methyltransferase complex
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;protein binding;zinc ion binding;histone demethylase activity;histone demethylase activity (H3-K4 specific);histone demethylase activity (H3-trimethyl-K4 specific);dioxygenase activity