SETD5

Chr 3AD

SET domain containing 5

Also known as: MRD23, SETD5A

The protein is predicted to function as a histone methyltransferase based on its SET domain. Mutations cause intellectual developmental disorder, autosomal dominant 23 through a loss-of-function mechanism. The condition follows an autosomal dominant inheritance pattern.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismADLOEUF 0.231 OMIM phenotype
Clinical SummarySETD5
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Gene-Disease Validity (ClinGen)
syndromic complex neurodevelopmental disorder · ADDefinitive

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.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.23LOEUF
pLI 1.000
Z-score 6.70
OE 0.13 (0.080.23)
Highly constrained

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

Missense Constraint
1.13Z-score
OE missense 0.89 (0.830.94)
683 obs / 771.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.13 (0.080.23)
00.351.4
Missense OE0.89 (0.830.94)
00.61.4
Synonymous OE1.05
01.21.6
LoF obs/exp: 9 / 69.1Missense obs/exp: 683 / 771.5Syn Z: -0.68
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveSETD5-related intellectual developmental disorderLOFAD
DN
0.2399th %ile
GOF
0.2098th %ile
LOF
0.88top 5%

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

LOFprediction above median · 1 literature citation · LOEUF 0.23

Literature Evidence

LOFHaploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition.PMID:30455454

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

SETD5 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗