KDM5C

Chr XXLR

lysine demethylase 5C

Also known as: DXS1272E, JARID1C, MRX13, MRXJ, MRXS16, MRXSCJ, MRXSJ, SMCX

This protein is a histone demethylase that regulates gene transcription and chromatin remodeling through its DNA-binding domains. Loss-of-function mutations cause X-linked intellectual developmental disorder, Claes-Jensen type, inherited in an X-linked recessive pattern. The high constraint scores (pLI 0.999, LOEUF 0.166) indicate the gene is highly intolerant to loss-of-function variants, consistent with pathogenic mutations disrupting normal chromatin regulation.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismXLRLOEUF 0.171 OMIM phenotype
Clinical SummaryKDM5C
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Gene-Disease Validity (ClinGen)
X-linked syndromic intellectual disability · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.17LOEUF
pLI 1.000
Z-score 6.38
OE 0.07 (0.040.17)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
5.15Z-score
OE missense 0.44 (0.400.48)
293 obs / 666.9 exp
Constrained

Extremely missense-constrained (top ~0.01%)

Observed / Expected Ratios
LoF OE0.07 (0.040.17)
00.351.4
Missense OE0.44 (0.400.48)
00.61.4
Synonymous OE1.05
01.21.6
LoF obs/exp: 4 / 55.1Missense obs/exp: 293 / 666.9Syn Z: -0.58
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveKDM5C-related syndromic intellectual developmental disorderLOFXLR
DN
0.2599th %ile
GOF
0.5367th %ile
LOF
0.72top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.17

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

KDM5C · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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