SMYD4

protein-coding

SET and MYND domain containing 4, the group of SET domain containing|Zinc fingers MYND-type

Gene summary

Enables protein-lysine N-methyltransferase activity. Involved in heart development. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_052928.3

Inheritance

—

ClinVar variants

U:135B:19

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.78

Max pathogenic AF

—

Genomic locus

chr17:1,779,485-1,830,634

External References & Databases

Ensembl (ENSG00000186532)

Transcript & Mutation Effects

hg38 • Region Span ~51.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SMYD4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 143

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_052928.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar			3
missense			129 clinvar	19 clinvar		148
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	135	19	0	154

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 35 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_052928.3	RefSeq	NP_443160.2	10	MANE Select
ENST00000305513.12	Ensembl	ENSP00000304360.7	10	MANE Select
ENST00000491788.1	Ensembl	ENSP00000460921.1	6	Standard
ENST00000570368.5	Ensembl	ENSP00000459819.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Histone Modifications

Biological Process

methylation

Molecular Function

methyltransferase activity
metal ion binding

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000305513
Coding exons: 10
Length: 51150
Individuals with no LoFs: 125476
Homozygous LoFs: 0
Heterozygous LoFs: 272
Defined: 125748
p: 0.00108

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.00749	462	462	1.00	0.0000262	5239
Missense (PolyPhen)		110	134.23	0.8195		1586
Synonymous	0.227	183	187	0.979	0.0000118	1587
Loss of Function	1.21	26	33.5	0.775	0.00000160	405

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00088	0.00086	rare
Latino/Admixed American	0.00035	0.00035	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.0016	0.0016	notable
Finnish	0.00030	0.00028	rare
European (Non-Finnish)	0.0017	0.0016	notable
South Asian	0.00052	0.00052	rare
Other	0.0010	0.00098	rare

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

LoFtool: 0.920
RVIS EVS: 1.41
RVIS percentile EVS: 94.8

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.335

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High