SMTNL1

Summary

SMTNL1 (smoothelin like 1, HGNC:32394) is a protein-coding gene on chromosome 11q12.1, encoding Smoothelin-like protein 1 (A8MU46). Plays a role in the regulation of contractile properties of both striated and smooth muscles.

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.

Source: NCBI Gene 219537 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 84 total
• MANE Select transcript: NM_001105565

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32394
Approved symbol	SMTNL1
Name	smoothelin like 1
Location	11q12.1
Locus type	gene with protein product
Status	Approved
Aliases	CHASM
Ensembl gene	ENSG00000214872
Ensembl biotype	protein_coding
OMIM	613664
Entrez	219537

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000527972

RefSeq mRNA: 1 — MANE Select: NM_001105565 NM_001105565

CCDS: CCDS44599

Canonical transcript exons

ENST00000527972 — 8 exons

Exon	Start	End
ENSE00001536715	57546501	57546652
ENSE00001536717	57546233	57546347
ENSE00001536718	57545881	57546036
ENSE00001536721	57543869	57543920
ENSE00001536723	57543624	57543756
ENSE00002154135	57549968	57550272
ENSE00003558129	57542641	57543374
ENSE00003928755	57537595	57537642

Expression profiles

Bgee: expression breadth ubiquitous, 164 present calls, max score 99.13.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.4870 / max 633.4361, expressed in 56 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
114277	1.0936	46
114276	0.3934	39

Top tissues by expression

252 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.13	gold quality
skeletal muscle tissue	UBERON:0001134	98.11	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.06	gold quality
vastus lateralis	UBERON:0001379	98.00	gold quality
biceps brachii	UBERON:0001507	97.98	gold quality
quadriceps femoris	UBERON:0001377	97.85	gold quality
body of tongue	UBERON:0011876	97.77	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.28	gold quality
gastrocnemius	UBERON:0001388	96.97	gold quality
deltoid	UBERON:0001476	96.73	gold quality
tibialis anterior	UBERON:0001385	95.72	silver quality
muscle of leg	UBERON:0001383	95.42	gold quality
muscle tissue	UBERON:0002385	89.62	gold quality
tongue	UBERON:0001723	86.85	gold quality
pharyngeal mucosa	UBERON:0000355	77.55	gold quality
buccal mucosa cell	CL:0002336	76.69	gold quality
superior surface of tongue	UBERON:0007371	75.99	gold quality
trabecular bone tissue	UBERON:0002483	70.64	gold quality
pancreatic ductal cell	CL:0002079	68.56	silver quality
upper arm skin	UBERON:0004263	67.96	gold quality
monocyte	CL:0000576	67.84	gold quality
sperm	CL:0000019	67.65	gold quality
leukocyte	CL:0000738	66.91	gold quality
myocardium	UBERON:0002349	66.90	gold quality
mucosa of stomach	UBERON:0001199	65.72	gold quality
oral cavity	UBERON:0000167	65.64	gold quality
apex of heart	UBERON:0002098	65.04	gold quality
blood	UBERON:0000178	64.96	gold quality
granulocyte	CL:0000094	64.36	gold quality
cortical plate	UBERON:0005343	63.70	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.42

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

4 targeting SMTNL1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-6836-3P	97.08	64.99	712

Literature-anchored findings (GeneRIF, showing 3)

• The Smtnl1 proximal promoter enhances expression up to 8-fold in smooth muscle cells and a second activating region lays 500 bp further upstream. (PMID:21352594)
• Pregnancy promotes switching of skeletal muscle to a glycolytic phenotype through the smoothelin-like protein 1 transcriptional cofactor. (PMID:26048986)
• Smoothelin-Like Protein 1 Regulates Development and Metabolic Transformation of Skeletal Muscle in Hyperthyroidism. (PMID:34675885)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Smtnl1	ENSMUSG00000027077
rattus_norvegicus	Smtnl1	ENSRNOG00000007516
drosophila_melanogaster	Ehbp1	FBGN0034180

Paralogs (7): ASPM (ENSG00000066279), MICALL1 (ENSG00000100139), EHBP1 (ENSG00000115504), GAS2 (ENSG00000148935), MICALL2 (ENSG00000164877), EHBP1L1 (ENSG00000173442), GAS2L1 (ENSG00000185340)

Protein

Protein identifiers

Smoothelin-like protein 1 — A8MU46 (reviewed: A8MU46)

All UniProt accessions (1): A8MU46

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Interacts with PPP1R12A.

Subcellular location. Cytoplasm. Myofibril. Sarcomere. I band. M line. Nucleus.

Tissue specificity. Expressed in striated muscles, specifically in type 2a fibers (at protein level).

Post-translational modifications. Maximal phosphorylation of Ser-336 correlates with maximal relaxation of aorta in response to acetylcholine.

Similarity. Belongs to the smoothelin family.

RefSeq proteins (1): NP_001099035* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001715	CH_dom	Domain
IPR036872	CH_dom_sf	Homologous_superfamily
IPR050540	F-actin_Monoox_Mical	Family

Pfam: PF00307

UniProt features (14 total): compositionally biased region 8, region of interest 2, chain 1, domain 1, modified residue 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A8MU46-F1	56.70	0.23

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 336

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 75 (showing top): GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_POSITIVE_REGULATION_OF_VASOCONSTRICTION, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GOBP_MUSCLE_ORGAN_MORPHOGENESIS, GOBP_REGULATION_OF_SYSTEM_PROCESS, GOBP_REGULATION_OF_VASOCONSTRICTION, GOBP_VASCULAR_PROCESS_IN_CIRCULATORY_SYSTEM, GOBP_REGULATION_OF_BLOOD_CIRCULATION, GOBP_RESPONSE_TO_ACTIVITY, GOCC_I_BAND, GOBP_POSITIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOCC_M_BAND, GOCC_A_BAND

GO Biological Process (6): response to xenobiotic stimulus (GO:0009410), response to activity (GO:0014823), vasoconstriction (GO:0042310), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of vasoconstriction (GO:0045907), muscle organ morphogenesis (GO:0048644)

GO Molecular Function (6): calmodulin binding (GO:0005516), tropomyosin binding (GO:0005523), protein phosphatase 1 binding (GO:0008157), CH domain binding (GO:0051401), disordered domain specific binding (GO:0097718), protein binding (GO:0005515)

GO Cellular Component (6): nucleus (GO:0005634), cytoplasm (GO:0005737), M band (GO:0031430), I band (GO:0031674), contractile muscle fiber (GO:0043292), myofibril (GO:0030016)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
protein domain specific binding	2
response to chemical	1
response to stimulus	1
blood vessel diameter maintenance	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
regulation of vasoconstriction	1
vasoconstriction	1
positive regulation of multicellular organismal process	1
muscle organ development	1
animal organ morphogenesis	1
protein binding	1
cytoskeletal protein binding	1
protein phosphatase binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
A band	1
sarcomere	1
cytoplasm	1
intracellular membraneless organelle	1
supramolecular fiber	1
contractile muscle fiber	1

Protein interactions and networks

STRING

580 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SMTNL1	PPP1R12A	O14974	803
SMTNL1	PRKG1	P14619	797
SMTNL1	RNF208	Q9H0X6	520
SMTNL1	FASTKD3	Q14CZ7	481
SMTNL1	SMTN	P53814	432
SMTNL1	CTNND1	O60716	409
SMTNL1	PGR	P06401	398
SMTNL1	PDLIM3	Q53GG5	392
SMTNL1	KRTAP19-1	Q8IUB9	370
SMTNL1	TNFRSF10D	Q9UBN6	348
SMTNL1	SMPX	Q9UHP9	348
SMTNL1	AKNAD1	Q5T1N1	336
SMTNL1	KDM6B	O15054	318
SMTNL1	LRCH4	O75427	317
SMTNL1	C2CD2L	O14523	315

IntAct

5 interactions, top by confidence:

A	B	Type	Score
SMTNL1	H1-10	psi-mi:“MI:0915”(physical association)	0.400
SMTNL1	SH3GL1	psi-mi:“MI:0915”(physical association)	0.400
ADAMTS13	C2CD4B	psi-mi:“MI:0914”(association)	0.350
CEP250	SMTNL1	psi-mi:“MI:0914”(association)	0.350

ESM2 similar proteins: A0A1B0GR13, A0A571BEE2, A8MU46, E9Q9K5, F1QBY1, O01949, O02828, O43493, P05229, P06719, P08855, P09346, P10156, P12036, P12305, P12675, P20810, P20811, P27321, P29172, P35662, P35663, P38978, P51125, P54938, P57786, P70486, P82179, Q02752, Q05018, Q05019, Q09202, Q09355, Q13061, Q14093, Q27450, Q28092, Q28820, Q54IN6, Q55H65

Diamond homologs: A5D7D1, A8MU46, D3ZEN0, D3ZHV2, D3ZQL6, D4A1F2, E1BBG2, E7F9T0, F1MF74, F1QH17, F1QWK4, F1RA39, F6QZ15, G3MWR8, G3V7L1, L7UZ85, M9MRD1, O13728, O15020, O43707, O76329, O88990, O94851, O97592, P05094, P05095, P11277, P11530, P11531, P11532, P11533, P12814, P15508, P18091, P20111, P30427, P35609, P46939, P53814, P57780

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

84 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	81
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1188 predictions. Top by Δscore:

Variant	Effect	Δscore
11:57543369:G:GT	donor_gain	1.0000
11:57543371:GGCA:G	donor_gain	1.0000
11:57543372:GCAG:G	donor_gain	1.0000
11:57543375:G:GG	donor_gain	1.0000
11:57543389:A:T	donor_gain	1.0000
11:57543425:G:GT	donor_gain	1.0000
11:57543447:G:GG	donor_gain	1.0000
11:57543457:A:T	donor_gain	1.0000
11:57543753:ACAGG:A	donor_loss	1.0000
11:57543754:CAGG:C	donor_loss	1.0000
11:57543757:G:GA	donor_loss	1.0000
11:57545880:GT:G	acceptor_gain	1.0000
11:57545880:GTGA:G	acceptor_gain	1.0000
11:57546344:CGAGG:C	donor_loss	1.0000
11:57546345:GAGG:G	donor_loss	1.0000
11:57546346:AGG:A	donor_loss	1.0000
11:57546348:GTGG:G	donor_loss	1.0000
11:57546349:T:G	donor_loss	1.0000
11:57546489:T:TA	acceptor_gain	1.0000
11:57546493:T:A	acceptor_gain	1.0000
11:57546498:TAGCA:T	acceptor_loss	1.0000
11:57546499:A:AG	acceptor_gain	1.0000
11:57546499:AGCAT:A	acceptor_gain	1.0000
11:57546500:G:GG	acceptor_gain	1.0000
11:57546500:GC:G	acceptor_gain	1.0000
11:57546500:GCAT:G	acceptor_gain	1.0000
11:57546500:GCATG:G	acceptor_gain	1.0000
11:57546648:GCAGA:G	donor_gain	1.0000
11:57546650:AGAG:A	donor_loss	1.0000
11:57546651:GA:G	donor_gain	1.0000

AlphaMissense

3248 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:57546531:T:A	W407R	1.000
11:57546531:T:C	W407R	1.000
11:57546318:T:A	W387R	0.999
11:57546318:T:C	W387R	0.999
11:57546320:G:C	W387C	0.999
11:57546320:G:T	W387C	0.999
11:57546323:C:G	C388W	0.999
11:57546528:A:C	S406R	0.999
11:57546530:C:A	S406R	0.999
11:57546530:C:G	S406R	0.999
11:57546532:G:C	W407S	0.999
11:57546533:G:C	W407C	0.999
11:57546533:G:T	W407C	0.999
11:57546541:G:A	G410D	0.999
11:57546541:G:T	G410V	0.999
11:57546554:T:G	C414W	0.999
11:57546556:C:A	A415D	0.999
11:57546570:T:C	F420L	0.999
11:57546572:C:A	F420L	0.999
11:57546572:C:G	F420L	0.999
11:57546626:C:A	N438K	0.999
11:57546626:C:G	N438K	0.999
11:57546639:T:C	F443L	0.999
11:57546640:T:C	F443S	0.999
11:57546641:C:A	F443L	0.999
11:57546641:C:G	F443L	0.999
11:57550042:T:A	V472D	0.999
11:57550063:T:C	L479P	0.999
11:57550075:T:C	L483P	0.999
11:57546310:T:C	L384P	0.998

dbSNP variants (sampled 300 via entrez): RS1000044799 (11:57547623 G>A), RS1000223759 (11:57537355 C>T), RS1000338301 (11:57548391 T>C), RS1000588555 (11:57535744 C>T), RS1000645034 (11:57542327 C>A,T), RS1000946820 (11:57546712 C>T), RS1001074642 (11:57540128 G>C), RS1001125420 (11:57540498 A>G), RS1001176559 (11:57536570 T>C), RS1001587410 (11:57546429 T>C,G), RS1001589403 (11:57547032 G>A,C), RS1001638517 (11:57549518 TTTTAA>T), RS1001773191 (11:57540869 C>A,T), RS1001929934 (11:57548531 G>A,T), RS1002162364 (11:57542033 C>T)

Disease associations

OMIM: gene MIM:613664 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006946_6	Worry too long after an embarrassing experience	1.000000e-11
GCST006951_1	Feeling hurt	2.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009589	worry measurement
EFO:0009599	feeling emotionally hurt measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.