KDM5B

Gene Facts

• HGNC Symbol: KDM5B (HGNC:18039)
• HGNC Name: lysine demethylase 5B
• Gene type: protein-coding gene
• Locus type: gene with protein product
• Previous symbols: JARID1B
• Alias symbols: RBBP2H1A, PLU-1, CT31, PPP1R98
• %HI: 28
• pLI: 0
• LOEUF: 0.86
• Cytoband: 1q32.1
• Genomic Coordinates:

  GRCh37/hg19:	chr1:202693623-202778598
  GRCh38/hg38:	chr1:202724495-202808421

• MANE Select Transcript: NM_006618.5 ENST00000367265.9
• Function: Histone demethylase that demethylates 'Lys-4' of histone H3, thereby playing a central role in histone code (PubMed:24952722, PubMed:27214403, PubMed:28262558). Does not demethylate histone H3 'Lys-9' or H3 'Lys-27'. Demethylates trimethylated, dimethylated and monomethylated H3 'Lys-4'. Acts as a transcriptional corepressor for FOXG1B and PAX9. Favors the proliferation of breast cancer cells by repressing tumor suppressor genes such as BRCA1 and HOXA5 (PubMed:24952722). In contrast, may act as ... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

• Dosage ID: ISCA-33224
• ClinGen Curation ID: CCID:007359
• Curation Status: Complete
• Issue Type: Dosage Curation - Gene
• Haploinsufficiency: Little Evidence for Haploinsufficiency (1)
• Triplosensitivity: No Evidence for Triplosensitivity (0)
• Last Evaluated: 01/04/2018

Haploinsufficiency (HI) Score Details

• HI Score: 1
• HI Evidence Strength: Little Evidence for Haploinsufficiency

HI Evidence

• PUBMED: 24307393
  Authors did whole genome and targeted sequencing in 9 patients with isolated intellectual disability (ID) of variable degrees without any copy number variations using SNP microarray. The 9 patients were selected from an initial cohort of 236 ID patients which had a medical record review and were determined to have isolated ID based on inclusion criteria set by authors. A de novo splice site mutation in trio 2 was identified suggesting that KDM5B may be a possible ID related candidate gene. No functional studies were performed.
• PUBMED: 28720891
  Authors used whole exome sequencing in an attempt to identify risk genes or rare variants in a cohort of 19 proband-parent trios from singleton families with autism spectrum disorder from Saudi Arabia. Among the 19 probands, one proband (Patient 19) was found to have a de novo nonsense variant p.Y755X in the KDM5B gene. No functional studies were performed.
• PUBMED: 25363768
  Whole exome sequencing of the Simons simplex collection including unaffected sibling and parent in each family was done. Results showed KDM5B as one of the recurrently mutated genes. Figure 2 and supplementary Table 2 showed a total of 4 de novo mutations in KDM5B identified in four ASD probands (2 likely gene disrupting and 2 missense) and 4 occurring in unaffected siblings (2 likely gene disrupting and 2 missense) . None of the 8 individuals appear to be related based on family ID in Table 2. No functional studies or further discussion on KDM5B was done.

• HI Evidence Comments: Additional PMID:28263302 identified a single de novo frame shift insertion (predicted to cause a loss of function,LOF) in a patient from an individual with autism spectrum disorder. PMID:25363760 performed whole exome sequencing on 15,480 DNA samples. Authors identified 1 de novo LOF variant and 1 missense variant , 4 inherited LOF variants, 19 inherited missense variants all in ASD patients. A total of 34 case-control cases were identified with KDM5B variants. Case-controls include 10 affected patients ( 1 LOF, 9 missense) and 24 unaffected (7 LOF, 17 missense). Due to the frequency of variants seen in controls a score of 1 has been given at this time.

Triplosensitivity (TS) Score Details

• TS Score: 0
• TS Evidence Strength: No Evidence for Triplosensitivity