SMTNL1

protein-coding

smoothelin like 1

Gene summary

The protein encoded by this gene is involved in the contraction of both striated and smooth muscle. During pregnancy, the encoded protein interacts with progesterone receptor to attenuate the expression of contractile and metabolic proteins. [provided by RefSeq, Jul 2016]

MANE transcript

NM_001105565.3

Inheritance

—

ClinVar variants

U:83

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.9

Max pathogenic AF

—

Genomic locus

chr11:57,537,595-57,550,272

External References & Databases

Ensembl (ENSG00000214872)

Transcript & Mutation Effects

hg38 • Region Span ~12.7 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 SMTNL1 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 81

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001105565.3. 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						0
missense			83 clinvar			83
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	83	0	0	83

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001105565.3	RefSeq	NP_001099035.2	7	MANE Select
ENST00000527972.6	Ensembl	ENSP00000432651.1	7	MANE Select
ENST00001140545.1	Ensembl	ENSP00000813755.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

actin cytoskeleton organization
positive regulation of vasoconstriction
negative regulation of blood vessel diameter

Molecular Function

calmodulin binding
tropomyosin binding
protein phosphatase 1 binding

Cellular Component

nucleus
cytoplasm
microtubule organizing center
M band
I band

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000457912
Coding exons: 8
Length: 9130
Individuals with no LoFs: 125141
Homozygous LoFs: 0
Heterozygous LoFs: 506
Defined: 125647
p: 0.00202

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.426	271	291	0.930	0.0000161	3312
Missense (PolyPhen)		72	86.472	0.83264		945
Synonymous	-1.21	132	115	1.14	0.00000705	983
Loss of Function	0.408	19	21.0	0.904	9.67e-7	286

Population LoF Frequency

Population	CAF	p-value	Status
African	0.011	0.0096	notable
Latino/Admixed American	0.0071	0.0070	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00072	0.00065	rare
Finnish	0.00010	0.000092	rare
European (Non-Finnish)	0.00064	0.00062	rare
South Asian	0.00062	0.00056	rare
Other	0.0014	0.0013	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a role in the regulation of contractile properties of both striated and smooth muscles. When unphosphorylated, may inhibit myosin dephosphorylation. Phosphorylation at Ser-299 reduces this inhibitory activity (By similarity). {ECO:0000250}.;

Essentials

Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.238

Gene Damage Prediction

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