KDM5D

Chr Y

lysine demethylase 5D

Also known as: HY, HYA, JARID1D, SMCY

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.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.36
Clinical SummaryKDM5D
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
72 unique Pathogenic / Likely Pathogenic· 5 VUS of 125 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.36LOEUF
pLI 0.928
Z-score 3.71
OE 0.14 (0.060.36)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
-0.37Z-score
OE missense 1.07 (0.961.18)
259 obs / 242.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.14 (0.060.36)
00.351.4
Missense OE1.07 (0.961.18)
00.61.4
Synonymous OE1.39
01.21.6
LoF obs/exp: 3 / 21.6Missense obs/exp: 259 / 242.7Syn Z: -2.81
DN
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

125 submitted variants in ClinVar

Classification Summary

Pathogenic70
Likely Pathogenic2
VUS5
Likely Benign5
70
Pathogenic
2
Likely Pathogenic
5
VUS
5
Likely Benign

Curated Variants Distribution

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

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
70
Likely Pathogenic
2
VUS
5
Likely Benign
5
Benign
0
Total82

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

KDM5D · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC