KDM5C |
- 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)
Haploinsufficiency (HI) Score Details
- X-linked syndromic intellectual disability Monarch
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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.
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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.
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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.
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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.
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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.
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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.
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
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.