KDM5D

Chr Y

lysine demethylase 5D

Also known as: HY, HYA, JARID1D, SMCY

NCBI Gene: 8284 ENSG00000012817 UniProt: Q9BY66

The encoded protein is a histone demethylase that specifically removes methyl groups from lysine-4 of histone H3, playing a central role in gene expression regulation and transcriptional repression. KDM5D is located on the Y chromosome and follows Y-linked inheritance, meaning mutations are passed from fathers to sons only. The gene is highly constrained against loss-of-function variants, but specific disease associations have not been established in the provided data.

ResearchSummary from RefSeq, UniProt

This gene encodes a protein containing zinc finger domains. A short peptide derived from this protein is a minor histocompatibility antigen which can lead to graft rejection of male donor cells in a female recipient. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2009]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.36

Clinical Summary— KDM5D

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.93). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

43 total variants — no pathogenic classifications of 43 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.36LOEUF

pLI 0.928

Z-score 3.71

OE 0.14 (0.06–0.36)

Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

-0.37Z-score

OE missense 1.07 (0.96–1.18)

259 obs / 242.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.14 (0.06–0.36)

0≤0.351.4

Missense OE?1.07 (0.96–1.18)

0≤0.61.4

Synonymous OE?1.39

0≤1.21.6

LoF obs/exp: 3 / 21.6Missense obs/exp: 259 / 242.7Syn Z: -2.81

This gene — mechanism propensity

0.3693th %ile

GOF

0.4875th %ile

LOF

0.68top 10%

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

LOFprediction above median · LOEUF 0.36

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

43 submitted variants in ClinVar

ClinVar

Classification Summary

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

Classification	LoF	Missense + Inframe	Non-coding	Synonymous
Pathogenic	—	—	—	—
Likely Pathogenic	—	—	—	—
VUS	—	—	—	—
Likely Benign	—	—	—	—
Benign	—	—	—	—
Total	—

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

72 pathogenic / likely-pathogenic (of 82) ClinVar copy-number / structural variants overlap KDM5D — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →