JARID2

jumonji and AT-rich interaction domain containing 2, the group of AT-rich interaction domain containing|Iron (II) and 2-oxoglutarate dependent oxygenases

Basic information

Region (hg38): 6:15246069-15522042

Previous symbols: [ "JMJ" ]

Links

ENSG00000008083 ∙ NCBI:3720 ∙ OMIM:601594 ∙ HGNC:6196 ∙ Uniprot:Q92833 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• developmental delay with variable intellectual disability and dysmorphic facies (Definitive), mode of inheritance: AD
• developmental delay with variable intellectual disability and dysmorphic facies (Strong), mode of inheritance: AD
• syndromic intellectual disability (Supportive), mode of inheritance: AD
• developmental delay with variable intellectual disability and dysmorphic facies (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental delay with variable intellecutal disability and dysmorphic facies	AD	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; Musculoskeletal; Neurologic	33077894; 35533077; 35887345

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the JARID2 gene.

• Inborn_genetic_diseases (166 variants)
• not_provided (115 variants)
• JARID2-related_disorder (29 variants)
• Developmental_delay_with_variable_intellectual_disability_and_dysmorphic_facies (27 variants)
• not_specified (6 variants)
• Neurodevelopmental_disorder (3 variants)
• JARID2-associated_Neurodevelopmental_disorder (2 variants)
• JARID2-related_Neurodevelopmental_syndrome (1 variants)
• JARID2-related_Neurodevelopmental_Disorder (1 variants)
• Stereotypic_movement_disorder (1 variants)
• Speech_apraxia (1 variants)
• Intellectual_disability (1 variants)
• Microcephaly (1 variants)
• See_cases (1 variants)
• Autism (1 variants)
• Autosomal_dominant_non-syndromic_intellectual_disability (1 variants)
• Mild_intellectual_disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the JARID2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004973.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			6	29	10	45
missense		1	221	35	4	261
nonsense	4	2	3			9
start loss		1				1
frameshift	10	4	2			16
splice donor/acceptor (+/-2bp)		2	6			8
Total	14	10	238	64	14

Highest pathogenic variant AF is 0.000004338282

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
JARID2	protein_coding	protein_coding	ENST00000341776	18	275726

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125739	0	9	125748	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.69	575	787	0.731	0.0000510	8125
Missense in Polyphen		117	243.77	0.47996		2466
Synonymous	-2.12	383	334	1.15	0.0000241	2482
Loss of Function	6.31	5	55.9	0.0894	0.00000291	654

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000617	0.0000615
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.000328	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Regulator of histone methyltransferase complexes that plays an essential role in embryonic development, including heart and liver development, neural tube fusion process and hematopoiesis. Acts by modulating histone methyltransferase activity and promoting the recruitment of histone methyltransferase complexes to their target genes. Binds DNA and mediates the recruitment of the PRC2 complex to target genes in embryonic stem cells. Does not have histone demethylase activity but regulates activity of various histone methyltransferase complexes. In embryonic stem cells, it associates with the PRC2 complex and inhibits trimethylation of 'Lys-27' of histone H3 (H3K27me3) by the PRC2 complex, thereby playing a key role in differentiation of embryonic stem cells and normal development. In cardiac cells, it is required to repress expression of cyclin-D1 (CCND1) by activating methylation of 'Lys-9' of histone H3 (H3K9me) by the GLP1/EHMT1 and G9a/EHMT2 histone methyltransferases. Also acts as a transcriptional repressor of ANF via its interaction with GATA4 and NKX2-5. Participates in the negative regulation of cell proliferation signaling. {ECO:0000269|PubMed:20075857}.
• Pathway: Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human);Endoderm Differentiation;Mesodermal Commitment Pathway;Interactome of polycomb repressive complex 2 (PRC2);Epigenetic regulation of gene expression;Gene expression (Transcription);PRC2 methylates histones and DNA (Consensus)

Recessive Scores

• pRec: 0.182

Intolerance Scores

• loftool: 0.0413
• rvis_EVS: -1.74
• rvis_percentile_EVS: 2.42

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.955

Gene Damage Prediction

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

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;liver development;chromatin remodeling;central nervous system development;negative regulation of cardiac muscle hypertrophy;histone demethylation;negative regulation of histone methylation;negative regulation of gene expression, epigenetic;negative regulation of transcription, DNA-templated;spleen development;thymus development;stem cell differentiation;positive regulation of histone H3-K9 methylation;negative regulation of cardiac muscle cell proliferation;cellular response to leukemia inhibitory factor
• Cellular component: nucleus;nucleoplasm;mitochondrion;histone methyltransferase complex;ESC/E(Z) complex
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;chromatin binding;transcription factor binding;histone demethylase activity;histone demethylase activity (H3-trimethyl-K4 specific)