• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
KDM5C (HGNC:11114) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
lysine demethylase 5C
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
SMCX, JARID1C, MRX13
Alias symbols
DXS1272E, XE169
%HI
11.71(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.17(Read more about gnomAD LOEUF score)
Cytoband
Xp11.22
Genomic Coordinates
GRCh37/hg19: chrX:53205459-53254389 NCBI Ensembl UCSC
GRCh38/hg38: chrX:53176277-53225207 NCBI Ensembl UCSC
MANE Select Transcript
NM_004187.5 ENST00000375401.8 (Read more about MANE Select)
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-BMAL1 heterodimer-m... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-3959
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
07/27/2023

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • X-linked syndromic intellectual disability Monarch
HI Evidence:
  • PUBMED: 15586325
    Jensen et al. (2005) report 3 families with X-linked intellectual disability (XLID) in affected males and loss of function variants in KDM5C (JARID1C), including one frameshift (Family ID D034) and two nonsense variants (Family ID P018 and N063). One of the nonsense variants (Family P018) and the frameshift variant (Family D034) were inherited from unaffected mothers. In the family with the other nonsense variant (Family N063), inheritance was not confirmed. This family also had an affected female sibling with the variant. Transcripts were not detected with either of the nonsense variants but were found with the frameshift suggesting a possible insensitivity to non-sense mediated decay for that variant. The authors also report four families with XLID males with missense variants in KDM5C.
  • PUBMED: 18697827
    Abidi et al. (2008) report two males with XLID who have a KDM5C frameshift variant that was also present in their unaffected sister and mother. Skewed X-inactivation was shown for the sister and mother. They also report an adopted male with XLID who had a c.1583+5G>A variant that produced abnormal transcripts and resulted in a frameshift and truncated protein.
  • PUBMED: 19826449
    Rujirabanjerd et al. (2010) report a family with three brothers with XLID who had a frameshift variant that was inherited from a mother with learning difficulties. The resulting transcript was not degraded. They also provide a review of previously reported variants.
  • PUBMED: 21575681
    Santos-Reboucas et al. (2011) report a family of three affected males with a nonsense variant in KDM5C and severe XLID, short stature, speech delay, hyperactivity, violent behavior and high palate. The variant was inherited from their mother with mild cognitive impairment. Reduced transcript levels were reported.
  • PUBMED: 31419599
    Guerra et al. (2020) report two monozygotic male twins and their older brother with a frameshift variant in KDM5C and severe XLID. The variant was inherited from their unaffected mother who showed completely skewed X-inactivation.
  • PUBMED: 35904121
    Levy et al. (2022) included a cohort of 58 cases with Intellectual developmental disorder, X-linked, syndromic, Claes–Jensen type (MRXSCJ), including 14 with KDM5C nonsense or frameshift variants, in their study of genome-wide DNA methylation profiles in individuals with neurodevelopmental disorders. Phenotypic and inheritance information were not provided.
HI Evidence Comments:
KDM5C gene, located at Xp11.22, has been associated with X-linked syndromic intellectual disability (XLID) (ClinGen Clinical Validity Framework, 9/17/2018). Additional loss of function variants have been reported in males with XLID (PMID:16541399, 25649377, 32581362, 35904121). Missense variants that segregate with XLID or autism have been reported as well (PMID: 16541399, 22326837, 16538222, 18203167).
NOTE:

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
NOTE:

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

Genomic View

Select assembly: (NC_000023.10) (NC_000023.11)