SMTN

protein-coding

smoothelin

Gene summary

This gene encodes a structural protein that is found exclusively in contractile smooth muscle cells. It associates with stress fibers and constitutes part of the cytoskeleton. This gene is localized to chromosome 22q12.3, distal to the TUPLE1 locus and outside the DiGeorge syndrome deletion. Alternative splicing of this gene results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, May 2011]

MANE transcript

NM_134269.3

Inheritance

—

ClinVar variants

U:167B:10

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.42

Max pathogenic AF

—

Genomic locus

chr22:31,064,105-31,104,757

External References & Databases

Ensembl (ENSG00000183963)

Transcript & Mutation Effects

hg38 • Region Span ~40.7 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 SMTN variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 176

not providedTotal: 9

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_134269.3. 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 clinvar		6
missense			161 clinvar	4 clinvar	3 clinvar	168
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	167	7	3	177

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 98 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_134269.3	RefSeq	NP_599031.1	19	MANE Select
ENST00000333137.12	Ensembl	ENSP00000329532.7	19	MANE Select
NM_001207017.1	RefSeq	NP_001193946.1	21	Standard
NM_001207018.2	RefSeq	NP_001193947.1	19	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

smooth muscle contraction
muscle organ development
actin cytoskeleton organization

Molecular Function

actin binding
structural constituent of muscle

Cellular Component

cytoplasm
microtubule organizing center
cytoskeleton
actin cytoskeleton
filamentous actin

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000358743
Coding exons: 20
Length: 40653
Individuals with no LoFs: 125703
Homozygous LoFs: 0
Heterozygous LoFs: 45
Defined: 125748
p: 0.000179

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.791	558	613	0.910	0.0000416	5938
Missense (PolyPhen)		181	221.27	0.81801		2046
Synonymous	1.63	212	244	0.867	0.0000153	2033
Loss of Function	3.73	20	47.9	0.418	0.00000300	481

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.000088	0.000087	rare
Ashkenazi Jewish	0.00030	0.00030	rare
East Asian	0.00023	0.00022	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00023	0.00022	rare
South Asian	0.00023	0.00023	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Structural protein of the cytoskeleton.;

Recessive Scores

pRec: 0.135

Intolerance Scores

LoFtool: 0.675
RVIS EVS: 0.43
RVIS percentile EVS: 77.33

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.259

Gene Damage Prediction

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