SMYD5

protein-coding

SMYD family member 5, the group of Zinc fingers MYND-type|SET domain containing

Gene summary

Enables protein-lysine N-methyltransferase activity. Involved in positive regulation of cytoplasmic translational elongation; regulation of stem cell differentiation; and transposable element silencing by heterochromatin formation. Is active in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

RAI15

MANE transcript

NM_006062.3

Inheritance

—

ClinVar variants

U:66B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.32

Max pathogenic AF

—

Genomic locus

chr2:73,214,222-73,227,221

External References & Databases

Ensembl (ENSG00000135632)

Transcript & Mutation Effects

hg38 • Region Span ~13.0 kb

Loading mutation effect viewer...

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 SMYD5 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 65

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006062.3. 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					1 clinvar	1
missense			63 clinvar	2 clinvar	1 clinvar	66
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	66	2	2	70

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 26 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006062.3	RefSeq	NP_006053.2	13	MANE Select
ENST00000389501.9	Ensembl	ENSP00000374152.4	13	MANE Select
ENST00000258100.8	Ensembl	ENSP00000258100.4	3	Standard
ENST00000413491.5	Ensembl	ENSP00000388195.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Histone Modifications

Biological Process

biological_process
methylation

Molecular Function

molecular_function
methyltransferase activity
metal ion binding

Cellular Component

cellular_component

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000389501
Coding exons: 13
Length: 13016
Individuals with no LoFs: 125692
Homozygous LoFs: 0
Heterozygous LoFs: 56
Defined: 125748
p: 0.000223

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.19	192	244	0.786	0.0000132	2766
Missense (PolyPhen)		83	93.079	0.89172		1105
Synonymous	-1.15	101	87.3	1.16	0.00000421	770
Loss of Function	3.18	8	25.3	0.317	0.00000116	291

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00058	0.00058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0.00037	0.00037	rare
European (Non-Finnish)	0.00012	0.00011	rare
South Asian	0.00020	0.00020	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.106

Intolerance Scores

LoFtool: 0.518
RVIS EVS: -0.05
RVIS percentile EVS: 50.01

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.915

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium