SETD5 (Q9C0A6) variants and mutations

SETD5 (also known as Q9C0A6) is a human protein-coding gene encoding a histone-lysine N-methyltransferase protein. It participates in chromatin-associated transcriptional regulation and is especially important during neurodevelopment. Haploinsufficiency causes a neurodevelopmental disorder with intellectual disability, speech delay, behavioral abnormalities, and variable congenital anomalies. This analysis covers 2,081 SETD5 variants and mutations. Of these, 67% have computational variant effect predictions. Disease context includes intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficie, hereditary disease, and autosomal dominant non-syndromic intellectual disability. Example SETD5 variants include M1?, I3T, and I3V.

Variant analysis overview

Gene: SETD5
Protein: Q9C0A6
UniProt accession: Q9C0A6
Organism: Homo sapiens
Variants analyzed: 2081
Variant scope: all variants
Completed: 2026-08-19

Variant and mutation evidence

Variant composition: 1,945 unspecified-consequence records; 71 missense variants; 41 synonymous variants; 9 frameshift variants; 9 stop-gained variants; 3 splice-region variants; 1 stop lost; 2 substitution
Prediction scores: 1,389 variants have prediction scores (67% of the analyzed set).

Clinical, disease, and population context

Disease context: 25 disease associations are represented. Top associations: intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficie, hereditary disease, autosomal dominant non-syndromic intellectual disability, Intellectual disability, neurodegenerative disease, neurodevelopmental disorder, developmental disability, KBG syndrome, Neurodevelopmental abnormality, type 2 diabetes mellitus, Abnormal facial shape, syndromic complex neurodevelopmental disorder.

Protein structure and variant hotspots

Protein features: 1 domains; 5 post-translational modification sites.
Structural context: 126 variants have structural context.
PTM context: 8 variants overlap post-translational modification sites.

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.

Notable SETD5 variants

Examples include M1?, I3T, I3V, A4S, A4T, A4V, A4A, I5N. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

SETD5 analysis run — SETD5 (2,081 variants) — completed 2026-08-19