KDM4C

Chr 9

lysine demethylase 4C

Also known as: GASC1, JHDM3C, JMJD2C, TDRD14C

NCBI Gene: 23081 ENSG00000107077 UniProt: Q9H3R0 OMIM: 605469

The KDM4C protein is a histone demethylase that specifically removes trimethyl groups from lysine-9 and lysine-36 residues of histone H3, playing a central role in gene expression regulation through chromatin modification. Mutations in this gene cause intellectual disability with dysmorphic features, which follows an autosomal dominant inheritance pattern. The condition typically involves developmental delays and distinctive facial features, representing a relatively recently described neurodevelopmental disorder.

OMIM ResearchSummary from RefSeq, UniProt

This gene is a member of the Jumonji domain 2 (JMJD2) family. The encoded protein is a trimethylation-specific demethylase, and converts specific trimethylated histone residues to the dimethylated form. This enzymatic action regulates gene expression and chromosome segregation. Chromosomal aberrations and changes in expression of this gene may be found in tumor cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

OMIM ResearchGenerating clinical summary…

LOEUF 0.54

Clinical Summary— KDM4C

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

152 VUS of 201 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.54LOEUF

pLI 0.000

Z-score 4.34

OE 0.37 (0.27–0.54)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

-0.49Z-score

OE missense 1.06 (0.99–1.13)

622 obs / 588.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.37 (0.27–0.54)

0≤0.351.4

Missense OE?1.06 (0.99–1.13)

0≤0.61.4

Synonymous OE?1.21

0≤1.21.6

LoF obs/exp: 21 / 56.1Missense obs/exp: 622 / 588.6Syn Z: -2.39

ClinVar Variant Classifications

201 submitted variants in ClinVar

ClinVar

Classification Summary

VUS152

Likely Benign11

Benign6

152

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	1	150	1	0	152
Likely Benign	0	7	0	4	11
Benign	0	1	0	5	6
Total	1	158	1	9	169

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

159 pathogenic / likely-pathogenic (of 210) ClinVar copy-number / structural variants overlap KDM4C — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →