STRN

Summary

STRN (striatin, HGNC:11424) is a protein-coding gene on chromosome 2p22.2, encoding Striatin (O43815). Calmodulin-binding scaffolding protein which is the center of the striatin-interacting phosphatase and kinase (STRIPAK) complexes.

Enables armadillo repeat domain binding activity; nuclear estrogen receptor binding activity; and protein phosphatase 2A binding activity. Involved in Wnt signaling pathway and negative regulation of cell population proliferation. Located in bicellular tight junction. Part of FAR/SIN/STRIPAK complex.

Source: NCBI Gene 6801 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 28 (top 5% of genes corpus-wide)
• Clinical variants (ClinVar): 131 total
• GTEx eGene: eQTL in 24 tissues, sQTL in 1 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.69 (unconstrained)
• MANE Select transcript: NM_003162
• Notable: 131 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11424
Approved symbol	STRN
Name	striatin
Location	2p22.2
Locus type	gene with protein product
Status	Approved
Aliases	PPP2R6A, STRN1
Ensembl gene	ENSG00000115808
Ensembl biotype	protein_coding
OMIM	614765
Entrez	6801

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 9 protein_coding, 4 nonsense_mediated_decay, 1 retained_intron

MANE Select: ENST00000263918

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2

ENST00000263918, ENST00000495595, ENST00000874611, ENST00000874612, ENST00000927774, ENST00000950119, ENST00000950120, ENST00000950121, ENST00000950122, ENST00000981987, ENST00000981988, ENST00000981989, ENST00001039085, ENST00001140353

RefSeq mRNA: 1 — MANE Select: NM_003162 NM_003162

CCDS: CCDS1784

Canonical transcript exons

ENST00000263918 — 18 exons

Exon	Start	End
ENSE00000747017	36851000	36851107
ENSE00000747019	36855212	36855352
ENSE00000747020	36857856	36858023
ENSE00000747021	36861132	36861253
ENSE00000747022	36867814	36867861
ENSE00000747024	36869554	36869729
ENSE00000747028	36883932	36884075
ENSE00000747038	36902584	36902751
ENSE00000747040	36905540	36905618
ENSE00000747042	36916078	36916151
ENSE00000747045	36925105	36925208
ENSE00001140050	36966230	36966536
ENSE00001831767	36837698	36849625
ENSE00002479130	36849714	36849800
ENSE00003471071	36886716	36886826
ENSE00003492685	36899523	36899658
ENSE00003594649	36893898	36894033
ENSE00003655689	36877891	36878027

Expression profiles

Bgee: expression breadth ubiquitous, 272 present calls, max score 96.67.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.8927 / max 1085.4831, expressed in 1801 samples.

Highest expression (Bgee): endothelial cell, amniotic fluid, corpus callosum, gingival epithelium, esophagus squamous epithelium.

Genetic regulation across tissues (GTEx eQTL / sQTL)

STRN is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 24 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 25 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Adipose Subcutaneous	eqtl	1.4e-21	+0.23	2:36973596:A:T
Esophagus Mucosa	eqtl	1.0e-17	+0.16	2:36953064:C:A
Whole Blood	eqtl	3.7e-16	+0.14	2:36909980:C:G
Thyroid	eqtl	2.2e-14	+0.23	2:36987936:G:C
Heart Left Ventricle	eqtl	5.4e-14	+0.17	2:36965352:T:C
Cells EBV-transformed lymphocytes	eqtl	2.7e-13	-0.32	2:36836097:C:CT
Esophagus Muscularis	eqtl	4.4e-10	+0.20	2:36987936:G:C
Heart Atrial Appendage	eqtl	3.4e-09	+0.20	2:36906949:C:A
Nerve Tibial	eqtl	3.9e-09	+0.16	2:36973596:A:T
Artery Tibial	eqtl	4.0e-08	+0.15	2:36965464:T:C
Adipose Visceral Omentum	eqtl	9.4e-08	+0.19	2:36999176:G:A
Colon Sigmoid	eqtl	1.3e-07	+0.18	2:36972890:G:A
Spleen	eqtl	8.0e-06	+0.21	2:36973596:A:T
Esophagus Gastroesophageal Junction	eqtl	8.1e-06	+0.19	2:36965464:T:C
Breast Mammary Tissue	eqtl	5.3e-05	+0.15	2:36993471:A:C
Cells Cultured fibroblasts	eqtl	6.7e-05	-0.08	2:36883902:T:A
Colon Transverse	eqtl	2.9e-04	+0.11	2:36973596:A:T
Skin Sun Exposed Lower leg	eqtl	1.5e-03	+0.08	2:37051063:T:A
Testis	eqtl	2.1e-03	+0.08	2:36973596:A:T
Skin Not Sun Exposed Suprapubic	eqtl	4.1e-03	+0.09	2:36921087:T:A

FANTOM5 promoters

8 alternative TSS:

Promoter ID	TPM avg	Samples expressed
27755	13.9929	1792
27750	1.6207	85
27756	1.0398	609
27754	0.5576	300
27749	0.3365	81
27752	0.1965	58
27753	0.0865	41
27751	0.0621	41

Top tissues by expression

showing 100 of 299 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	96.67	gold quality
amniotic fluid	UBERON:0000173	96.50	gold quality
corpus callosum	UBERON:0002336	95.78	gold quality
gingival epithelium	UBERON:0001949	95.24	gold quality
esophagus squamous epithelium	UBERON:0006920	95.18	gold quality
gingiva	UBERON:0001828	93.59	gold quality
calcaneal tendon	UBERON:0003701	92.91	gold quality
oral cavity	UBERON:0000167	92.77	gold quality
inferior vagus X ganglion	UBERON:0005363	92.21	gold quality
germinal epithelium of ovary	UBERON:0001304	91.98	gold quality
subthalamic nucleus	UBERON:0001906	91.14	gold quality
colonic epithelium	UBERON:0000397	90.76	gold quality
Brodmann (1909) area 23	UBERON:0013554	90.70	gold quality
tendon	UBERON:0000043	89.72	gold quality
parietal pleura	UBERON:0002400	89.22	gold quality
tibia	UBERON:0000979	89.06	gold quality
heart right ventricle	UBERON:0002080	88.75	gold quality
lateral globus pallidus	UBERON:0002476	88.64	gold quality
visceral pleura	UBERON:0002401	88.23	gold quality
buccal mucosa cell	CL:0002336	88.15	gold quality
tonsil	UBERON:0002372	88.07	gold quality
epithelium of esophagus	UBERON:0001976	88.06	gold quality
pleura	UBERON:0000977	88.01	gold quality
globus pallidus	UBERON:0001875	87.63	gold quality
medial globus pallidus	UBERON:0002477	87.27	gold quality
epithelium of nasopharynx	UBERON:0001951	87.01	gold quality
substantia nigra pars reticulata	UBERON:0001966	86.76	gold quality
adrenal tissue	UBERON:0018303	86.64	gold quality
squamous epithelium	UBERON:0006914	85.95	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	85.36	gold quality
spinal cord	UBERON:0002240	85.22	gold quality
palpebral conjunctiva	UBERON:0001812	85.18	gold quality
jejunal mucosa	UBERON:0000399	85.00	gold quality
dorsal plus ventral thalamus	UBERON:0001897	84.67	gold quality
superior vestibular nucleus	UBERON:0007227	84.62	gold quality
lower esophagus mucosa	UBERON:0035834	84.25	gold quality
primary visual cortex	UBERON:0002436	84.23	gold quality
eye	UBERON:0000970	84.22	gold quality
upper leg skin	UBERON:0004262	84.12	gold quality
mucosa of sigmoid colon	UBERON:0004993	84.08	gold quality
middle temporal gyrus	UBERON:0002771	84.01	gold quality
substantia nigra pars compacta	UBERON:0001965	84.00	gold quality
pons	UBERON:0000988	83.94	gold quality
sural nerve	UBERON:0015488	83.93	gold quality
esophagus mucosa	UBERON:0002469	83.60	gold quality
colonic mucosa	UBERON:0000317	83.58	gold quality
occipital lobe	UBERON:0002021	83.12	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.00	gold quality
ventral tegmental area	UBERON:0002691	82.97	gold quality
rectum	UBERON:0001052	82.68	gold quality
mucosa of paranasal sinus	UBERON:0005030	82.57	gold quality
stromal cell of endometrium	CL:0002255	82.48	gold quality
bone marrow	UBERON:0002371	82.48	gold quality
penis	UBERON:0000989	82.33	gold quality
tendon of biceps brachii	UBERON:0008188	82.24	silver quality
mammary duct	UBERON:0001765	82.00	gold quality
monocyte	CL:0000576	81.99	gold quality
islet of Langerhans	UBERON:0000006	81.99	gold quality
cardiac ventricle	UBERON:0002082	81.78	gold quality
gastrocnemius	UBERON:0001388	81.65	gold quality
heart left ventricle	UBERON:0002084	81.62	gold quality
pharyngeal mucosa	UBERON:0000355	81.60	gold quality
skin of hip	UBERON:0001554	81.57	gold quality
mononuclear cell	CL:0000842	81.41	gold quality
leukocyte	CL:0000738	81.38	gold quality
muscle of leg	UBERON:0001383	81.32	gold quality
lateral nuclear group of thalamus	UBERON:0002736	80.96	gold quality
mammary gland	UBERON:0001911	80.86	gold quality
pigmented layer of retina	UBERON:0001782	80.78	gold quality
thoracic mammary gland	UBERON:0005200	80.78	gold quality
retina	UBERON:0000966	80.76	gold quality
mouth mucosa	UBERON:0003729	80.62	gold quality
jejunum	UBERON:0002115	80.44	gold quality
biceps brachii	UBERON:0001507	80.42	gold quality
heart	UBERON:0000948	80.36	gold quality
mammalian vulva	UBERON:0000997	80.04	gold quality
medulla oblongata	UBERON:0001896	79.96	gold quality
lower lobe of lung	UBERON:0008949	79.89	gold quality
entorhinal cortex	UBERON:0002728	79.86	gold quality
parietal lobe	UBERON:0001872	79.78	gold quality
superior surface of tongue	UBERON:0007371	79.77	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.69	gold quality
renal medulla	UBERON:0000362	79.53	gold quality
postcentral gyrus	UBERON:0002581	79.33	gold quality
trabecular bone tissue	UBERON:0002483	79.30	gold quality
minor salivary gland	UBERON:0001830	79.28	gold quality
ventricular zone	UBERON:0003053	79.16	gold quality
superior frontal gyrus	UBERON:0002661	79.08	gold quality
epithelium of mammary gland	UBERON:0003244	79.06	gold quality
prefrontal cortex	UBERON:0000451	79.04	gold quality
esophagus	UBERON:0001043	79.03	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	78.95	gold quality
vagina	UBERON:0000996	78.88	gold quality
endometrium	UBERON:0001295	78.75	gold quality
duodenum	UBERON:0002114	78.56	gold quality
gall bladder	UBERON:0002110	78.50	gold quality
bone marrow cell	CL:0002092	78.43	gold quality
skeletal muscle organ	UBERON:0014892	78.36	gold quality
muscle organ	UBERON:0001630	78.34	gold quality
caudate nucleus	UBERON:0001873	78.30	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.85

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Corpus callosum	tissue	182.6
Spinal cord	tissue	120.2
Medulla oblongata	tissue	100.8
Putamen	tissue	99.8
Midbrain	tissue	94.8
Caudate putamen	tissue	93.6
Substantia nigra	tissue	87.2
Thalamus	tissue	76.8
Superior colliculi	tissue	74.8
Pons	tissue	73.9
Ventral forebrain	tissue	73.9
Periaqueductal gray	tissue	67.5
Hippocampal formation	tissue	58.8
Septum	tissue	56.0
Basal ganglia	tissue	55.9	medium
Hypothalamus	tissue	54.0
Nucleus accumbens	tissue	46.5
Cerebral cortex	tissue	46.2	medium
Occipital cortex	tissue	46.2
Somatosensory cortex	tissue	45.5
Retrosplenial cortex	tissue	44.6
Motor cortex	tissue	42.0
Olfactory bulb	tissue	41.7
Amygdala	tissue	39.4
Retrosplenial and cingulate cortex	tissue	39.0
Cerebellum	tissue	38.7	medium
Prefrontal cortex	tissue	38.1
Entorhinal cortex	tissue	37.0
Insular cortex	tissue	36.9
Temporal cortex	tissue	36.3
Postcentral gyrus	tissue	32.3
Hippocampus	tissue	30.5	medium
Locus coeruleus	tissue	27.4
Choroid plexus	tissue	23.1
Heart muscle	tissue	19.9	medium
Esophagus	tissue	19.9	high
Frontal cortex	tissue	18.3
Bone marrow	tissue	14.1	medium
Thymus	tissue	12.4
Tonsil	tissue	11.8	high
Tongue	tissue	10.7
Rectum	tissue	10.1	high
Retina	tissue	9.4
Placenta	tissue	9.4	high
Appendix	tissue	8.9	high
Salivary gland	tissue	8.6	medium
Stomach 1	tissue	8.5	high
Colon	tissue	8.5	medium
Small intestine	tissue	8.1	high
Breast	tissue	8.0	medium
Adipose tissue	tissue	7.8	low
Urinary bladder	tissue	7.8	medium
Kidney	tissue	7.8	medium
Skin 1	tissue	7.6	medium
Spleen	tissue	7.6	medium
Duodenum	tissue	7.6	high
Testis	tissue	7.5	medium
Lung	tissue	7.4	medium
Vagina	tissue	7.3	medium
Lymph node	tissue	7.2	high

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — White matter (182.6), Ventral spinal cord (120.2), Dorsal spinal cord (100.8), Parieto-temporal junction (white matter) (72.0), Corpus callosum, genu (white matter) (67.6).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting STRN by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 554 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-5193	100.00	67.26	1744
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-1252-5P	100.00	69.80	2774

Functional genomics

gnomAD constraint: pLI 2.99e-06, LOEUF 0.686, missense Z -0.864 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000263918 — one region, missense o/e 1.02.

Literature-anchored findings (GeneRIF, showing 20)

• identify striatin as a molecular scaffold required for rapid, nongenomic estrogen-mediated activation of downstream signaling pathways (PMID:15569929)
• Taken together, splicing variation of SG2NA might have some critical roles in differentiation and maturation in metazoan cells. (PMID:18571342)
• Using shotgun mass spectrometry, we found this protein differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19165527)
• Striatin orchestrates the regulation of Mst3 by PP2A. (PMID:21985334)
• A recurrent STRN/ALK fusion found in thyroid carcinomas. (PMID:24475247)
• Our data demonstrate that STRN-ALK fusion occurs in a subset of patients with highly aggressive types of thyroid cancer and provide initial evidence suggesting that it may represent a therapeutic target for these patients. (PMID:24613930)
• the rapid, nongenomic mineralocorticoid receptor pathway (mediated via striatin) has a role in modulating the interaction between salt intake and blood pressure. (PMID:25368024)
• PP2A/striatin complex modulates microtubule dynamics by regulating MAP2 phosphorylation (PMID:25497017)
• the “multimodulator” scaffold roles of striatins in the initiation and regulation of the formation of various complex particles and structures, are discussed. (PMID:25501894)
• we report 2 cases of renal cell carcinomas harboring a novel STRN-ALK fusion (PMID:26848800)
• In this review, we summarize the current understanding of the assembly and functions of STRIPAK complexes( striatin-centered multicomponent supramolecular structures containing both kinases and phosphatases), with a special focus on cell signaling and cancer (PMID:26876214)
• striatin-associated Salt Sensitive Blood Pressure is associated with normal plasma renin activity and reduced epinephrine levels (PMID:28985281)
• The prevalence of STRN-ALK kinase fusions were determined in papillary thyroid cancer of an adult population (PMID:29046324)
• STRN-ALK gene fusion is associated with radiation-associated Thyroid Cancer. (PMID:29165687)
• we detected novel and related STRN-NTRK3 and STRN3-NTRK3 fusions in 2 fibrosarcomas that occurred in the bone and soft tissue of young adult patients (PMID:30520818)
• Striatin genotype-based, mineralocorticoid receptor antagonist-driven clinical trial: study rationale and design. (PMID:33904521)
• ULK1 phosphorylation of striatin activates protein phosphatase 2A and autophagy. (PMID:34592149)
• Phosphorylation of Influenza A Virus Matrix Protein 1 at Threonine 108 Controls Its Multimerization State and Functional Association with the STRIPAK Complex. (PMID:36602306)
• Placental expression of striatin & endothelial nitric oxide synthase in women with & without pre-eclampsia. (PMID:37147942)
• Striatin Gene Variants Are Associated With Salt Sensitivity of Blood Pressure by Mechanisms That Differ in Women and Men. (PMID:38018471)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	strn	ENSDARG00000100011
mus_musculus	Strn	ENSMUSG00000024077
rattus_norvegicus	Strn	ENSRNOG00000004806
drosophila_melanogaster	Cka	FBGN0044323
caenorhabditis_elegans		WBGENE00010631

Paralogs (2): STRN4 (ENSG00000090372), STRN3 (ENSG00000196792)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1333757) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 3 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased circulating aldosterone level	1
increased systemic arterial blood pressure	1
embryonic lethality, complete penetrance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	A5D7H2	96.9%	Diamond
Oryza sativa Japonica Group	Q6ZJX0	88.3%	Diamond
Zea mays	Q8VZY6	88.3%	Diamond
Aspergillus nidulans FGSC A4	Q00659	80.8%	Diamond
Aspergillus clavatus NRRL 1	A1C7E4	80.6%	Diamond
Arabidopsis thaliana	Q9LT47	69.6%	Diamond
Debaryomyces hansenii CBS767	Q6BUA6	62.2%	Diamond
Chlamydomonas reinhardtii	A8IZG4	60.0%	Diamond
Neurospora crassa OR74A	Q9C270	56.8%	Diamond
Dictyostelium discoideum	Q54TD8	47.3%	Diamond
Schizosaccharomyces pombe 972h-	O74319	41.4%	Diamond
Nakaseomyces glabratus CBS 138	Q6FT96	40.8%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
CRIM1	protein-coding	51232
VIT	protein-coding	5212
FEZ2	protein-coding	9637
GPATCH11	protein-coding	253635
HEATR5B	protein-coding	54497
EIF2AK2	protein-coding	5610
SULT6B1	protein-coding	391365
CEBPZOS	protein-coding	100505876
CEBPZ	protein-coding	10153

Protein

Protein identifiers

Striatin — O43815 (reviewed: O43815)

All UniProt accessions (1): O43815

UniProt curated annotations — full annotation on UniProt →

Function. Calmodulin-binding scaffolding protein which is the center of the striatin-interacting phosphatase and kinase (STRIPAK) complexes. STRIPAK complexes have critical roles in protein (de)phosphorylation and are regulators of multiple signaling pathways including Hippo, MAPK, nuclear receptor and cytoskeleton remodeling. Different types of STRIPAK complexes are involved in a variety of biological processes such as cell growth, differentiation, apoptosis, metabolism and immune regulation.

Subunit / interactions. Part of the core of STRIPAK complexes composed of PP2A catalytic and scaffolding subunits, the striatins (PP2A regulatory subunits), the striatin-associated proteins MOB4, STRIP1 and STRIP2, PDCD10 and members of the STE20 kinases, such as STK24 and STK26. Interacts with CTTNBP2; this interaction may regulate dendritic spine distribution of STRN. Activation of glutamate receptors weakens the interaction with CTTNBP2.

Subcellular location. Cytoplasm. Membrane. Cell projection. Dendritic spine.

Tissue specificity. Preferentially expressed in brain.

Similarity. Belongs to the WD repeat striatin family.

Isoforms (2)

UniProt ID	Names	Canonical?
O43815-1	1	yes
O43815-2	2

RefSeq proteins (1): NP_003153* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR013258	Striatin_N	Domain
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR019775	WD40_repeat_CS	Conserved_site
IPR020472	WD40_PAC1	Repeat
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR051488	WD_repeat_striatin	Family

Pfam: PF00400, PF08232

UniProt features (26 total): repeat 6, modified residue 6, region of interest 5, sequence conflict 4, splice variant 2, chain 1, coiled-coil region 1, compositionally biased region 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43815-F1	68.70	0.41

Human Protein Atlas

Protein class: Predicted intracellular proteins, Cancer-related genes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; nucleoplasm

Antibody reliability (HPA): IH approved · IF approved

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 (6)

Type	Positions
Phosphoserine	137, 227, 229, 245, 259
Phosphothreonine	225

Function

Pathways and Gene Ontology

Reactome pathways

7 curated (TAS) of 17; 9 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

17 pathways:

ID	Pathway	Evidence
R-HSA-9700645	ALK mutants bind TKIs ⚕	curated
R-HSA-2219530	Constitutive Signaling by Aberrant PI3K in Cancer ⚕	curated
R-HSA-9725370	Signaling by ALK fusions and activated point mutants ⚕	curated
R-HSA-9673766	Signaling by cytosolic PDGFRA and PDGFRB fusion proteins ⚕	curated
R-HSA-9009391	Extra-nuclear estrogen signaling	curated
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	curated
R-HSA-1257604	PIP3 activates AKT signaling	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers ⚕	—
R-HSA-2219528	PI3K/AKT Signaling in Cancer ⚕	—
R-HSA-9700206	Signaling by ALK in cancer ⚕	—
R-HSA-9671555	Signaling by PDGFR in disease ⚕	—
R-HSA-8939211	ESR-mediated signaling	—
R-HSA-9006925	Intracellular signaling by second messengers	—
R-HSA-199418	Negative regulation of the PI3K/AKT network	—
R-HSA-162582	Signal Transduction	—
R-HSA-9006931	Signaling by Nuclear Receptors	—

MSigDB gene sets: 260 (showing top): GOBP_DENDRITE_DEVELOPMENT, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_BEHAVIOR, MODULE_255, GOBP_APICAL_JUNCTION_ASSEMBLY, MODULE_317, GOBP_NEUROGENESIS, GOBP_HIPPO_SIGNALING, CEBPB_01, ATGTTAA_MIR302C, GOBP_CELL_JUNCTION_ORGANIZATION, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, MODULE_99, RYTTCCTG_ETS2_B, GOBP_CELL_JUNCTION_ASSEMBLY

GO Biological Process (7): locomotory behavior (GO:0007626), negative regulation of cell population proliferation (GO:0008285), regulation of signal transduction (GO:0009966), Wnt signaling pathway (GO:0016055), dendrite development (GO:0016358), regulation of hippo signaling (GO:0035330), bicellular tight junction assembly (GO:0070830)

GO Molecular Function (7): calmodulin binding (GO:0005516), nuclear estrogen receptor binding (GO:0030331), protein-macromolecule adaptor activity (GO:0030674), protein-containing complex binding (GO:0044877), protein phosphatase 2A binding (GO:0051721), armadillo repeat domain binding (GO:0070016), protein binding (GO:0005515)

GO Cellular Component (12): cytosol (GO:0005829), bicellular tight junction (GO:0005923), postsynaptic density (GO:0014069), membrane (GO:0016020), dendrite (GO:0030425), neuronal cell body (GO:0043025), dendritic spine (GO:0043197), postsynaptic membrane (GO:0045211), FAR/SIP/STRIPAK complex (GO:0090443), postsynapse (GO:0098794), cytoplasm (GO:0005737), cell junction (GO:0030054)

Reactome top-level categories

11 top-level categories:

Category	Pathways
Diseases of signal transduction by growth factor receptors and second messengers	3
Signaling by ALK in cancer	2
Signal Transduction	2
Intracellular signaling by second messengers	1
PI3K/AKT Signaling in Cancer	1
Negative regulation of the PI3K/AKT network	1
ESR-mediated signaling	1
Signaling by PDGFR in disease	1
PIP3 activates AKT signaling	1
Disease	1
Signaling by Nuclear Receptors	1

GO top-level categories

38 GO namespaces:

Category	Terms
cellular anatomical structure	5
protein binding	2
binding	2
postsynapse	2
behavior	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
signal transduction	1
regulation of cell communication	1
regulation of signaling	1
regulation of response to stimulus	1
cell surface receptor signaling pathway	1
neuron projection development	1
anatomical structure development	1
hippo signaling	1
regulation of intracellular signal transduction	1
apical junction assembly	1
tight junction assembly	1
nuclear receptor binding	1
molecular adaptor activity	1
protein phosphatase binding	1
protein domain specific binding	1
cytoplasm	1
apical junction complex	1
tight junction	1
asymmetric synapse	1
postsynaptic specialization	1
neuron projection	1
dendritic tree	1
somatodendritic compartment	1
cell body	1
dendrite	1
neuron spine	1
synaptic membrane	1
protein-containing complex	1
synapse	1
intracellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 8 of 26 annotations. The rest are phylogenetic / computational / electronic (IEA).

8 experimentally-supported GO terms:

GO term	NS	Evidence
Wnt signaling pathway	BP	mutant phenotype
negative regulation of cell population proliferation	BP	mutant phenotype
FAR/SIP/STRIPAK complex	CC	direct assay
bicellular tight junction	CC	direct assay
armadillo repeat domain binding	MF	physical interaction
nuclear estrogen receptor binding	MF	physical interaction
protein phosphatase 2A binding	MF	direct assay
protein-containing complex binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,678 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STRN	MOB4	Q9Y3A3	987
STRN	STRIP1	Q5VSL9	800
STRN	STRIP2	Q9ULQ0	722
STRN	STK25	O00506	718
STRN	SLMAP	Q14BN4	710
STRN	PPP2R3A	Q06190	704
STRN	EML4	Q9HC35	700
STRN	PPP2R1A	P30153	695
STRN	MINK1	Q8N4C8	680
STRN	PDCD10	Q9BUL8	662
STRN	PPP2CA	P05323	655
STRN	ALK	Q9UM73	637
STRN	STK26	Q9P289	636
STRN	STK24	Q9Y6E0	627
STRN	SIKE1	Q9BRV8	621

IntAct

Human interaction partners of STRN in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 51 partners by confidence:

Partner	Interaction type	MIscore	Records
STK25	association	0.900	7
PPP2R1A	association	0.880	7
STRN3	physical association	0.880	6
STK24	physical association	0.870	4
STK26	physical association	0.860	3
PPP2CA	physical association	0.840	3
CTTNBP2NL	association	0.820	3
PDCD10	physical association	0.820	1
PPP2CB	association	0.790	4
MOB4	physical association	0.790	2
STRIP1	physical association	0.770	1
PPP2R1B	association	0.730	1
SIKE1	association	0.730	1
STRN4	association	0.730	1
SLMAP	association	0.710	2
TRAF3IP3	physical association	0.620	1
STK4	association	0.610	4
RINT1	physical association	0.560	3
TFIP11	physical association	0.560	3
MAP4K4	association	0.530	2
SPINK2	association	0.530	2
PRPF19	association	0.530	1
TCP1	association	0.530	1
TNKS2	direct interaction	0.520	2
STK3	proximity	0.480	2
Y0068	physical association	0.370	1
FLII	association	0.350	2
M	association	0.350	2
SNX24	association	0.350	2
ENDOD1	association	0.350	1

BioGRID (342 interactions; top human partners by supporting records): PPP2R1A (Affinity Capture-MS; 15 records), STRN3 (Affinity Capture-MS; 14 records), MOB4 (Affinity Capture-MS; 11 records), STK24 (Affinity Capture-MS; 10 records), CTTNBP2NL (Affinity Capture-MS; 9 records), PDCD10 (Affinity Capture-MS; 8 records), PPP2CA (Affinity Capture-MS; 8 records), PPP2CB (Affinity Capture-MS; 8 records), SLMAP (Affinity Capture-MS; 8 records), STK25 (Affinity Capture-MS; 8 records), STK26 (Affinity Capture-MS; 8 records), STRIP1 (Affinity Capture-MS; 8 records), SIKE1 (Affinity Capture-MS; 7 records), STRN4 (Affinity Capture-MS; 7 records), FGFR1OP2 (Affinity Capture-MS; 6 records)

SIGNOR signaling

3 signaling interactions:

A	Effect	B	Mechanism
CTTNBP2NL	“up-regulates activity”	STRN	binding
STRN	“up-regulates activity”	PPP2CA	binding
STRN	“up-regulates activity”	PPP2CB	binding

Protein complexes (CORUM) (2)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

2 complexes by size:

Complex	Subunits	Members
STRIPAK complex	11	PPP2CA, PPP2R1A, STRIP1, STRN, CTTNBP2NL, GOLGA2, MOB4, STK26, STRN3, STRN4, PDCD10
PP2A A/C-striatin complex	3	PPP2CA, PPP2R1A, STRN

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 51 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Degradation of beta-catenin by the destruction complex	5	36.0×	3e-06

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of hippo signaling	8	114.6×	6e-13
protein autophosphorylation	6	17.8×	6e-05
protein phosphorylation	8	11.1×	4e-05
intracellular signal transduction	11	8.6×	7e-06

Disease & clinical

Genetic variants

Variant evidence for STRN: 131 ClinVar records (0 pathogenic / likely pathogenic); 28 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	75
Likely benign	3
Benign	31

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 38 predictions of 2,176):

Position(s)	Effect	Δscore	Sites
2:36849626–36849627	acceptor_loss	1.0000	4
2:36849803	acceptor_gain	1.0000
2:36850998–36850999	donor_loss	1.0000	2
2:36851108–36851109	acceptor_loss	1.0000	6
2:36878028–36878029	acceptor_loss	1.0000	6
2:36886714–36886715	donor_loss	1.0000	5
2:36886742	donor_gain	1.0000
2:36893865	donor_gain	1.0000
2:36893896–36893897	donor_loss	1.0000	6
2:36894034–36894035	acceptor_loss	1.0000	6

AlphaMissense

2,314 missense substitutions predicted likely pathogenic (of 5,161 scored), across 501 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M104	9	0.988	1.000
M357	9	0.952	0.993
M702	9	0.940	0.997
D484	8	0.999	1.000
H705	8	0.999	1.000
D727	8	0.999	1.000
D97	8	0.998	0.999
D773	8	0.998	1.000
H462	8	0.997	0.999
H747	8	0.997	0.999
F471	8	0.992	0.999
H515	8	0.990	0.997
H568	8	0.988	0.996
H761	8	0.987	0.999
D464	8	0.986	0.998
D551	8	0.986	0.996
D715	8	0.986	0.997
H673	8	0.983	0.999
H726	8	0.981	0.993
D590	8	0.974	0.998

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	7.55e-07
Pancreatic Adenocarcinoma (TCGA)	unfavorable	0.00025

Disease associations

OMIM: gene MIM:614765 | disease phenotypes:

GWAS associations

28 associations:

Study	Trait	p-value
GCST90002395_199	Mean platelet volume	2e-53
GCST010703_139	Brain morphology (MOSTest)	6e-46
GCST010697_37	Cortical surface area (min-P)	6e-31
GCST010321_72	PR interval	1e-23
GCST010320_28	PR interval	6e-23
GCST010701_13	Cortical surface area (MOSTest)	4e-16
GCST010244_105	Triglyceride levels	3e-12
GCST010699_86	Brain morphology (min-P)	2e-11
GCST003844_43	QRS duration	5e-11
GCST90000025_456	Appendicular lean mass	7e-11
GCST004628_49	Immature fraction of reticulocytes	4e-10
GCST010346_32	TPE interval (resting)	8e-10
GCST010702_84	Subcortical volume (MOSTest)	1e-9
GCST003598_12	QRS duration	2e-9
GCST003598_4	QRS duration	2e-9
GCST010173_128	Triglyceride levels	5e-9
GCST90002404_12	Red cell distribution width	5e-9
GCST004612_57	High light scatter reticulocyte percentage of red cells	7e-9
GCST012490_359	Femur bone mineral density x serum urate levels interaction	9e-9
GCST010698_51	Subcortical volume (min-P)	1e-8
GCST010700_34	Cortical thickness (MOSTest)	2e-8
GCST010346_60	TPE interval (resting)	3e-8
GCST90011898_168	Alanine aminotransferase levels	3e-8
GCST005998_1	Alanine transaminase levels	4e-8
GCST012490_155	Femur bone mineral density x serum urate levels interaction	5e-8
GCST012099_10	Hypertrophic cardiomyopathy (sarcomere negative)	1e-7
GCST003901_16	Cognitive decline (age-related)	5e-6
GCST009391_113	Metabolite levels	7e-6

EFO canonical traits (from GWAS)

11 canonical traits:

EFO ID	Trait name
EFO:0005054	QRS complex
EFO:0007986	reticulocyte count
EFO:0010355	diacylglycerol 36:2 measurement
EFO:0004530	triglyceride measurement
EFO:0004462	PR interval
EFO:0004644	TPE interval measurement
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness
EFO:0004531	urate measurement
EFO:0004980	appendicular lean mass
EFO:0009188	Red cell distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

49 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases abundance, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Valproic Acid	decreases expression, decreases methylation	2
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
trichostatin A	increases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
coumarin	decreases phosphorylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	decreases expression	1
monomethylarsonous acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Acetaminophen	increases expression	1
Atrazine	increases expression	1
Vehicle Emissions	increases abundance, increases expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.