SMYD3

protein-coding

SET and MYND domain containing 3, the group of Lysine methyltransferases|Zinc fingers MYND-type|SET domain containing

Gene summary

This gene encodes a histone methyltransferase which functions in RNA polymerase II complexes by an interaction with a specific RNA helicase. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

Previous symbols:

ZNFN3A1
ZMYND1

MANE transcript

NM_001167740.2

Inheritance

—

ClinVar variants

U:69B:1

Top phenotype

Cerebellar dysfunction with variable cognitive and behavioral abnormalities

gnomAD constraint

pLI —, LoF o/e 0.58

Max pathogenic AF

—

Genomic locus

chr1:245,749,342-246,507,312

External References & Databases

Ensembl (ENSG00000185420)

Transcript & Mutation Effects

hg38 • Region Span ~758.0 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 SMYD3 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 61

not providedTotal: 3

Cerebellar dysfunction with variable cognitive and behavioral abnormalitiesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001167740.2. 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			2 clinvar		1 clinvar	3
missense			61 clinvar			61
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	69	0	1	70

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 32 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001167740.2	RefSeq	NP_001161212.1	12	MANE Select
ENST00000490107.6	Ensembl	ENSP00000419184.2	12	MANE Select
NM_001375962.1	RefSeq	NP_001362891.1	11	Standard
NM_001375963.1	RefSeq	NP_001362892.1	11	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
smyd3	Danio rerio	Structure: trunk Quality: curved dorsal abnormal

Gene / Model

Organism

Observed Phenotype

smyd3

Danio rerio

Structure: trunk

Quality: curved dorsal

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Histone Modifications
PKMTs methylate histone lysines
Chromatin modifying enzymes
Lysine metabolism
Chromatin organization

Biological Process

nucleosome assembly
negative regulation of protein kinase activity
myotube cell development
positive regulation of peptidyl-serine phosphorylation
histone lysine methylation

Molecular Function

RNA polymerase II proximal promoter sequence-specific DNA binding
RNA polymerase II complex binding
RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding
protein binding
histone-lysine N-methyltransferase activity

Cellular Component

nucleus
nucleoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000388985
Coding exons: 12
Length: 757973
Individuals with no LoFs: 125659
Homozygous LoFs: 0
Heterozygous LoFs: 89
Defined: 125748
p: 0.000354

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.245	225	236	0.955	0.0000126	2815
Missense (PolyPhen)		63	65.148	0.96703		778
Synonymous	-0.0406	87	86.5	1.01	0.00000469	777
Loss of Function	1.96	15	25.7	0.584	0.00000141	291

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.00042	0.00038	rare
Ashkenazi Jewish	0.0011	0.0011	notable
East Asian	0.00017	0.00016	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00044	0.00042	rare
South Asian	0.00026	0.00026	rare
Other	0.00034	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Histone methyltransferase. Specifically methylates 'Lys- 4' of histone H3, inducing di- and tri-methylation, but not monomethylation (PubMed:15235609, PubMed:22419068). Also methylates 'Lys-5' of histone H4 (PubMed:22419068). Plays an important role in transcriptional activation as a member of an RNA polymerase complex (PubMed:15235609). Binds DNA containing 5'- CCCTCC-3' or 5'-GAGGGG-3' sequences (PubMed:15235609). {ECO:0000269|PubMed:15235609, ECO:0000269|PubMed:22419068}.;

Recessive Scores

pRec: 0.114

Intolerance Scores

LoFtool: 0.960
RVIS EVS: -0.31
RVIS percentile EVS: 31.93

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.874

Gene Damage Prediction

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