MSN

Summary

MSN (moesin, HGNC:7373) is a protein-coding gene on chromosome Xq12, encoding Moesin (P26038). Ezrin-radixin-moesin (ERM) family protein that connects the actin cytoskeleton to the plasma membrane and thereby regulates the structure and function of specific domains of the cell cortex.

Moesin (for membrane-organizing extension spike protein) is a member of the ERM family which includes ezrin and radixin. ERM proteins appear to function as cross-linkers between plasma membranes and actin-based cytoskeletons. Moesin is localized to filopodia and other membranous protrusions that are important for cell-cell recognition and signaling and for cell movement.

Source: NCBI Gene 4478 — RefSeq curated summary.

At a glance

• Gene–disease (curated): combined immunodeficiency due to moesin deficiency (Definitive, ClinGen)
• GWAS associations: 1
• Clinical variants (ClinVar): 361 total — 12 pathogenic, 7 likely-pathogenic (top 9% of genes corpus-wide)
• Regional missense constraint (gnomAD): 1 of 5 regions constrained (≈5% of expected missense variation)
• GTEx eGene: eQTL in 17 tissues, sQTL in 5 (q < 0.05)
• Phenotypes (HPO): 7
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 4 cancer types (inferred from mutation patterns)
• MANE Select transcript: NM_002444
• Interaction hub: 2,704 STRING partners (top 3% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7373
Approved symbol	MSN
Name	moesin
Location	Xq12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000147065
Ensembl biotype	protein_coding
OMIM	309845
Entrez	4478

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 13 protein_coding, 5 protein_coding_CDS_not_defined, 5 nonsense_mediated_decay, 5 retained_intron

MANE Select: ENST00000360270

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 3: 1, TSL 4: 1, TSL 5: 2

ENST00000360270, ENST00000429601, ENST00000439474, ENST00000447323, ENST00000609205, ENST00000609672, ENST00000697133, ENST00000697134, ENST00000697135, ENST00000697136, ENST00000697137, ENST00000697138, ENST00000697139, ENST00000697140, ENST00000697141, ENST00000697142, ENST00000885865, ENST00000915048, ENST00000915049, ENST00000943362, ENST00000943363, ENST00001051599, ENST00001051600, ENST00001051601, ENST00001086309, ENST00001093695, ENST00001129737, ENST00001134443

RefSeq mRNA: 2 — MANE Select: NM_002444 NM_001440778, NM_002444

CCDS: CCDS14382

Canonical transcript exons

ENST00000360270 — 13 exons

Exon	Start	End
ENSE00000978535	65727814	65727909
ENSE00000978536	65729438	65729712
ENSE00000978537	65731107	65731190
ENSE00000978538	65731838	65731984
ENSE00000978539	65733184	65733280
ENSE00001022049	65736795	65736925
ENSE00001707735	65735267	65735430
ENSE00003496799	65738970	65739194
ENSE00003577013	65738525	65738617
ENSE00003596103	65737178	65737338
ENSE00003969704	65667654	65667853
ENSE00003969709	65716818	65716901
ENSE00003969728	65739729	65741931

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 99.55.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.3482 / max 290.9508, expressed in 1690 samples.

Highest expression (Bgee): lower lobe of lung, monocyte, leukocyte, mononuclear cell, granulocyte.

Genetic regulation across tissues (GTEx eQTL / sQTL)

MSN is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 17 tissues and its splicing (sQTL) in 5 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 22 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Not Sun Exposed Suprapubic	eqtl	2.0e-09	+0.43	X:65757188:T:C
Skin Sun Exposed Lower leg	eqtl	5.0e-08	+0.36	X:65619097:C:A
Esophagus Mucosa	eqtl	3.9e-05	+0.25	X:65757188:T:C
Artery Aorta	eqtl	6.1e-05	-0.08	X:65643655:C:G
Muscle Skeletal	eqtl	1.2e-03	+0.28	X:65757188:T:C
Breast Mammary Tissue	eqtl	1.4e-03	+0.17	X:65994525:G:A
Testis	eqtl	1.9e-03	+0.17	X:65926197:G:C
Thyroid	sqtl	1.9e-03	+0.68	X:66559518:C:T
Nerve Tibial	eqtl	2.6e-03	+0.22	X:65757188:T:C
Cells Cultured fibroblasts	eqtl	5.8e-03	-0.09	X:65329480:T:G
Esophagus Mucosa	sqtl	7.4e-03	-0.27	X:66330892:G:A
Brain Caudate basal ganglia	eqtl	9.0e-03	-0.30	X:64619052:A:G
Cells Cultured fibroblasts	sqtl	1.1e-02	+0.43	X:66566430:A:C
Brain Cerebellar Hemisphere	eqtl	1.6e-02	-0.22	X:65595044:G:C
Brain Nucleus accumbens basal ganglia	eqtl	1.7e-02	-0.27	X:66514832:G:A
Lung	eqtl	1.7e-02	+0.16	X:66113756:C:G
Heart Left Ventricle	eqtl	2.0e-02	+0.08	X:64814387:A:C
Testis	sqtl	2.6e-02	-0.70	X:66509076:T:A
Artery Tibial	eqtl	2.8e-02	+0.07	X:65857184:T:A
Brain Anterior cingulate cortex BA24	eqtl	2.8e-02	-0.17	X:66404428:G:T

FANTOM5 promoters

8 alternative TSS:

Promoter ID	TPM avg	Samples expressed
196538	12.8973	1629
196536	5.3659	1584
196539	3.5356	1383
196533	1.4178	415
196534	0.5121	82
196537	0.3335	145
196540	0.2455	125
196541	0.0405	11

Top tissues by expression

showing 100 of 295 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lower lobe of lung	UBERON:0008949	99.55	gold quality
monocyte	CL:0000576	99.40	gold quality
leukocyte	CL:0000738	99.40	gold quality
mononuclear cell	CL:0000842	99.39	gold quality
granulocyte	CL:0000094	99.38	gold quality
synovial joint	UBERON:0002217	99.36	gold quality
saphenous vein	UBERON:0007318	99.23	gold quality
layer of synovial tissue	UBERON:0007616	99.17	gold quality
right lung	UBERON:0002167	99.15	gold quality
vermiform appendix	UBERON:0001154	99.13	gold quality
blood vessel layer	UBERON:0004797	99.13	gold quality
lung	UBERON:0002048	99.11	gold quality
smooth muscle tissue	UBERON:0001135	99.09	gold quality
upper lobe of lung	UBERON:0008948	99.09	gold quality
blood	UBERON:0000178	99.05	gold quality
caecum	UBERON:0001153	99.05	gold quality
upper lobe of left lung	UBERON:0008952	99.05	gold quality
superficial temporal artery	UBERON:0001614	99.01	gold quality
right coronary artery	UBERON:0001625	98.98	gold quality
lymph node	UBERON:0000029	98.96	gold quality
thymus	UBERON:0002370	98.93	gold quality
descending thoracic aorta	UBERON:0002345	98.92	gold quality
trabecular bone tissue	UBERON:0002483	98.92	gold quality
thoracic aorta	UBERON:0001515	98.89	gold quality
ascending aorta	UBERON:0001496	98.88	gold quality
aorta	UBERON:0000947	98.86	gold quality
popliteal artery	UBERON:0002250	98.84	gold quality
tibial artery	UBERON:0007610	98.84	gold quality
decidua	UBERON:0002450	98.80	gold quality
penis	UBERON:0000989	98.75	gold quality
dorsal root ganglion	UBERON:0000044	98.74	gold quality
bone marrow cell	CL:0002092	98.72	gold quality
colonic epithelium	UBERON:0000397	98.68	gold quality
vena cava	UBERON:0004087	98.67	gold quality
coronary artery	UBERON:0001621	98.66	gold quality
left coronary artery	UBERON:0001626	98.63	gold quality
pericardium	UBERON:0002407	98.63	gold quality
adipose tissue	UBERON:0001013	98.57	gold quality
bone marrow	UBERON:0002371	98.55	gold quality
subcutaneous adipose tissue	UBERON:0002190	98.54	gold quality
stromal cell of endometrium	CL:0002255	98.53	gold quality
connective tissue	UBERON:0002384	98.53	gold quality
omental fat pad	UBERON:0010414	98.47	gold quality
urethra	UBERON:0000057	98.46	gold quality
peritoneum	UBERON:0002358	98.46	gold quality
adipose tissue of abdominal region	UBERON:0007808	98.46	gold quality
gall bladder	UBERON:0002110	98.45	gold quality
seminal vesicle	UBERON:0000998	98.43	gold quality
trigeminal ganglion	UBERON:0001675	98.42	gold quality
myometrium	UBERON:0001296	98.41	gold quality
cauda epididymis	UBERON:0004360	98.38	gold quality
renal medulla	UBERON:0000362	98.36	gold quality
left uterine tube	UBERON:0001303	98.33	gold quality
nipple	UBERON:0002030	98.30	gold quality
cartilage tissue	UBERON:0002418	98.26	gold quality
body of uterus	UBERON:0009853	98.25	gold quality
tibial nerve	UBERON:0001323	98.24	gold quality
middle frontal gyrus	UBERON:0002702	98.21	gold quality
ventricular zone	UBERON:0003053	98.21	gold quality
islet of Langerhans	UBERON:0000006	98.18	gold quality
spleen	UBERON:0002106	98.18	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.12	gold quality
lower esophagus	UBERON:0013473	98.11	gold quality
mucosa of stomach	UBERON:0001199	98.08	gold quality
right lobe of thyroid gland	UBERON:0001119	98.07	gold quality
left lobe of thyroid gland	UBERON:0001120	98.06	gold quality
thyroid gland	UBERON:0002046	98.05	gold quality
pylorus	UBERON:0001166	98.03	gold quality
calcaneal tendon	UBERON:0003701	98.02	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.02	gold quality
mammalian vulva	UBERON:0000997	97.99	gold quality
cardia of stomach	UBERON:0001162	97.99	gold quality
adult organism	UBERON:0007023	97.91	gold quality
trachea	UBERON:0003126	97.88	gold quality
metanephros cortex	UBERON:0010533	97.88	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.81	gold quality
choroid plexus epithelium	UBERON:0003911	97.81	gold quality
adult mammalian kidney	UBERON:0000082	97.78	gold quality
endocervix	UBERON:0000458	97.76	gold quality
urinary bladder	UBERON:0001255	97.76	gold quality
olfactory bulb	UBERON:0002264	97.74	gold quality
skin of hip	UBERON:0001554	97.69	gold quality
ectocervix	UBERON:0012249	97.47	gold quality
mammary duct	UBERON:0001765	97.42	gold quality
cardiac atrium	UBERON:0002081	97.36	gold quality
myocardium	UBERON:0002349	97.34	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.32	gold quality
right atrium auricular region	UBERON:0006631	97.30	gold quality
thoracic mammary gland	UBERON:0005200	97.29	gold quality
germinal epithelium of ovary	UBERON:0001304	97.25	gold quality
mammary gland	UBERON:0001911	97.24	gold quality
ganglionic eminence	UBERON:0004023	97.15	gold quality
paraflocculus	UBERON:0005351	97.13	gold quality
heart	UBERON:0000948	97.12	gold quality
left ventricle myocardium	UBERON:0006566	97.08	gold quality
upper arm skin	UBERON:0004263	97.03	gold quality
epithelium of mammary gland	UBERON:0003244	97.02	gold quality
skin of leg	UBERON:0001511	97.00	gold quality
spinal cord	UBERON:0002240	96.97	gold quality
tonsil	UBERON:0002372	96.87	gold quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	151.59
E-CURD-122	yes	40.59
E-HCAD-10	yes	32.09
E-CURD-112	yes	19.64
E-GEOD-93593	yes	13.94
E-MTAB-9388	yes	12.20
E-GEOD-81547	yes	8.00
E-GEOD-83139	yes	7.34
E-ENAD-27	yes	6.35
E-MTAB-5061	yes	5.83
E-GEOD-70580	no	1221.31
E-MTAB-6819	no	350.76
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 77 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Lung	tissue	257.9	medium
Appendix	tissue	239.8	medium
Smooth muscle	tissue	228.5	low
Bone marrow	tissue	225.4	high
Tonsil	tissue	222.1	high
Adipose tissue	tissue	192.4	not detected
Lymph node	tissue	188.6	high
Spleen	tissue	182.3	medium
Thymus	tissue	161.9
Urinary bladder	tissue	141.6	low
Placenta	tissue	139.4	medium
Thyroid gland	tissue	139.4	low
Kidney	tissue	120.7	medium
Endometrium 1	tissue	118.9	low
Seminal vesicle	tissue	117.2	low
Gallbladder	tissue	111.6	medium
Cervix	tissue	104.5	low
Heart muscle	tissue	104.1	not detected
Ovary	tissue	99.7	low
Vagina	tissue	93.8	not detected
Spinal cord	tissue	92.6
Locus coeruleus	tissue	84.9
Liver	tissue	81.3	not detected
Skin 1	tissue	81.1	medium
Choroid plexus	tissue	80.7
Esophagus	tissue	80.3	not detected
Fallopian tube	tissue	78.4	low
Rectum	tissue	70.4	not detected
Tongue	tissue	69.9
Adrenal gland	tissue	69.1	medium
Hypothalamus	tissue	67.9
Medulla oblongata	tissue	65.9
Substantia nigra	tissue	65.9
Breast	tissue	65.0	low
Colon	tissue	64.1	medium
Prostate	tissue	61.2	low
Midbrain	tissue	60.3
Periaqueductal gray	tissue	58.0
Hippocampus	tissue	57.5	medium
Pons	tissue	56.0
Superior colliculi	tissue	56.0
Thalamus	tissue	54.6
Stomach 1	tissue	53.7	not detected
Septum	tissue	53.7
Salivary gland	tissue	52.3	medium
Nucleus accumbens	tissue	51.9
Hippocampal formation	tissue	50.8
Small intestine	tissue	50.1	not detected
Corpus callosum	tissue	49.6
Amygdala	tissue	48.5
Basal ganglia	tissue	47.6	medium
Skeletal muscle	tissue	47.0	not detected
Putamen	tissue	46.7
Pituitary gland	tissue	46.3
Ventral forebrain	tissue	46.0
Entorhinal cortex	tissue	41.2
Epididymis	tissue	40.7	medium
Duodenum	tissue	40.5	not detected
Cerebral cortex	tissue	39.6	low
Motor cortex	tissue	39.6

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Blood vessel (249.5), Nucleus raphe pallidus (127.6), Area postrema (126.2), Medial olivary nucleus (122.6), Supraoptic nucleus (121.4).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets:

Target	Regulation
ICAM1	Activation

Upstream regulators (CollecTRI, top): MYC, ROCK2

miRNA regulators (miRDB)

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

showing 30 of 174 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
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-3064-3P	100.00	70.09	1254
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488

Functional genomics

Regional missense constraint (gnomAD)

ENST00000360270 splits into 5 regions with different missense tolerance; 1 is missense-constrained (≈5% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
X:65,667,842–65,731,869	89 / 151.0	0.59	no
X:65,731,870–65,731,967	2 / 22.6	0.09	yes (p 1.5e-05)
X:65,731,968–65,736,872	58 / 104.6	0.55	no
X:65,736,873–65,738,603	70 / 76.3	0.92	no
X:65,738,604–65,739,890	48 / 115.5	0.42	no

Literature-anchored findings (GeneRIF, showing 40)

• amino-terminal domains of the ezrin, radixin, and moesin (ERM) proteins bind advanced glycation end products and have a role in diabetes (PMID:12734202)
• PECAM-1 co-localized with moesin at the cell periphery and in filopodia of glass-activated platelets; moesin may play a role in platelet adhesion, linking PECAM-1 with the actin cytoskeleton (PMID:12850829)
• moesin has a role in lymph node metastasis of oral squamous cell carcinoma (PMID:14760079)
• important role in lipopolysaccharide-induced TNF-alpha production, particularly in lipopolysaccharide-mediated signal transduction (PMID:15039356)
• ezrin/radixin/moesin proteins are recruited by NHE1 Na+/H+ exchanger and have roles in regulating Akt-dependent cell survival (PMID:15096511)
• All three ERM family members can localise to the nucleus; a specific nuclear localisation sequence, which is conserved and functional in all ERM family members, is identified, implying specific regulated nuclear import. (PMID:15149851)
• there is nucleotide variation at Msn and Alas2 on the X chromosome (PMID:15166166)
• results suggest that ezrin-radixin-moesin proteins are required for microvillar positioning of L-selectin and that this is important both for leukocyte tethering and L-selectin shedding (PMID:15178693)
• Ezrin, radixin and moesin are ADP-ribosylated by Pseudomonas aeruginosa ExoS (PMID:15252013)
• Expression of ExoS in HeLa cells led to a loss of phosphorylation of Ezrin/radixin/moesin proteins that was dependent upon the expression of ADP-ribosyltransferase activity. (PMID:16889625)
• early phagosome maturation was shown to depend on activation of Rho acting through Rho kinase on ezrin-radixin-moesin proteins (PMID:16908865)
• B-cell response to moesin, possibly derived from hematopoietic cells, frequently occurs in patients with acquired aplastic anemia (PMID:17110458)
• moesin negatively regulates stable microtubule networks and is a natural determinant of cellular sensitivity to retroviral infection (PMID:17170707)
• increased CD44, ezrin, radixin, and moesin phosphorylation represents a key molecular abnormality that guides T cell adhesion and migration in SLE patients. (PMID:17237445)
• MSN was differentially expressed in sclerotic hippocampi compared to non-sclerotic ones. (PMID:17515952)
• Moesin protein expression is a basal marker in breast tumors. Moesin expression was nearly an independent prognostic marker of poor outcome (PMID:17594689)
• the ezrin, radixin, and moesin proteins function as positive regulators of infection by X4-tropic HIV-1 (PMID:18295815)
• Phosphorylation of ezrin/moesin by ROCK is involved in the early steps of apoptotic signaling following Fas receptor triggering and regulates apoptosis induction in Jurkat cells. (PMID:18941185)
• functional alterations of moesin may be involved in pathological disorders associated with clathrin-mediated internalization or receptor recycling (PMID:19047065)
• Results suggest that activated moesin promotes F-actin redistribution and CD4-CXCR4 clustering and is also required for efficient X4-tropic HIV-1 infection in permissive lymphocytes. (PMID:19066282)
• No aspects of T cell receptor signaling uniquely require transgenic ezrin or moesin; instead, T cell activation appears to depend on net ezrin, radixin, and moesin (ERM) protein expression, while ezrin and moesin function together. (PMID:19124745)
• In Vitro and in Vivo Characterization of Molecular Interactions between Calmodulin, Ezrin/Radixin/Moesin, and L-selectin (PMID:19129194)
• c14orf166 was identified asa novel metastasis-associated protein, and the roles of radixin, moesin and c14orf166 in pancreatic cancer metastasis deserve further investigations. (PMID:19152423)
• These studies identify a new ERM kinase of importance in lymphocytes and confirm the role of ezrin-radixin-moesin phosphorylation in regulating cell shape and motility. (PMID:19255442)
• Moesin is a phenotypic marker for anaplastic carcinoma. (PMID:19432821)
• expression of moesin delays senescence of human dermal microvascular endothelial cells (PMID:19555429)
• Moesin is crucial for invasion by melanoma cells in 3D matrices and in early lung colonization. (PMID:19723803)
• Data show that stimulation of the NK cell-expressed tetraspanin CD81 induces phosphorylation of ezrin/radixin/moesin proteins and leads to NK cell polarization thereby facilitating NK cell migration toward various chemokines/cytokines. (PMID:19830727)
• Ezrin, radixin, and moesin proteins are physiological substrates of the kinase activity of leucine-rich repeat kinase 2 (LRRK2). (PMID:19890007)
• Data show that TNF-alpha induces the formation of fibrotic foci by cultured retinal pigment epithelial cells through activation of transforming growth factor-TGF-beta signaling in a manner dependent on hyaluronan-CD44-moesin interaction. (PMID:19965872)
• Findings suggest that there is a functional association between moesin expression and cellular senescence. (PMID:20376899)
• Results suggest that VEGF-C promoted cervical cancer metastasis by upregulation and activation of moesin protein through RhoA/ROCK-2 pathway. (PMID:20429915)
• important role in the innate immune response and toll-like receptor 4-mediated pattern recognition in periodontal disease (PMID:20546116)
• Results demonstrate a new regulatory mechanism of ezrin-radixin-moesin phosphorylation by sphingolipids with opposing actions of ceramide and sphingosine 1-phosphate. (PMID:20679347)
• Data suggest that ezrin-radixin-moesin proteins are involved in the spatial regulation of Epac1 and cooperate with cAMP- and Rap-mediated signaling to regulate adhesion to the extracellular matrix. (PMID:20855527)
• This study provides the novel evidence that increased phosphorylation of Ezrin/radixin/moesin proteins may contribute to proliferation of rheumatoid fibroblast-like synoviocytes. (PMID:21278069)
• Dysregulation of the ezrin/radixin/moesin-RAGE complex might be an important step in rearrangement of the actin cytoskeleton during proinflammatory cytokine-induced epithelial-mesenchymal transition of human alveolar epithelial cells. (PMID:21278261)
• ezrin, radixin and moesin play similar roles in the tumor cell metastatic potential and their roles of upregulating the expression of E-cadherin may be important in tumor progression (PMID:21352885)
• Knockdown of ERM family member moesin in host cells increases HIV type 1 replication. (PMID:21486194)
• PDZD8 is a novel moesin-interacting protein that suppresses infection by herpes simplex virus type 1. (PMID:21549406)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	msnb	ENSDARG00000028740
danio_rerio	msna	ENSDARG00000058128
mus_musculus	Msn	ENSMUSG00000031207
rattus_norvegicus	Msn	ENSRNOG00000030118
drosophila_melanogaster	Moe	FBGN0011661

Paralogs (6): EZR (ENSG00000092820), FRMD4B (ENSG00000114541), ERMN (ENSG00000136541), RDX (ENSG00000137710), FRMD4A (ENSG00000151474), NF2 (ENSG00000186575)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:97167) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 18 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased hematocrit	1
decreased leukocyte cell number	1
decreased neutrophil cell number	1
overexpanded pulmonary alveolus	1
increased mean corpuscular volume	1
increased heart weight	1
decreased hemoglobin content	1
decreased erythrocyte cell number	1
thrombocytopenia	1
decreased eosinophil cell number	1
decreased lymphocyte cell number	1
decreased B cell number	1
increased susceptibility to injury	1
increased mean corpuscular hemoglobin	1
impaired pupillary reflex	1
decreased CD4-positive, alpha-beta T cell number	1
dilated respiratory conducting tube	1
impaired leukocyte migration	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
Papio anubis	P59750	99.8%	Diamond
Sus scrofa	P26044	99.3%	Diamond
Bos taurus	Q32LP2	99.3%	Diamond
Pongo abelii	Q5RAB8	98.1%	Diamond
Gallus gallus	Q9PU45	98.1%	Diamond
Canis lupus familiaris	Q6Q7P4	97.8%	Diamond
Drosophila pseudoobscura pseudoobscura	Q29GR8	95.5%	Diamond
Oryctolagus cuniculus	Q8HZQ5	94.9%	Diamond
Culex quinquefasciatus	B0WYY2	92.7%	Diamond
Anopheles gambiae	Q7PS12	92.7%	Diamond
Aedes aegypti	Q170J7	90.6%	Diamond
Lytechinus variegatus	P52962	80.2%	Diamond
Mesocricetus auratus	P86232	54.8%	Diamond
Dictyostelium discoideum	Q54EW0	31.6%	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
LAS1L	protein-coding	81887
ZC3H12B	protein-coding	340554

Protein

Protein identifiers

Moesin — P26038 (reviewed: P26038)

Alternative names: Membrane-organizing extension spike protein

All UniProt accessions (5): P26038, A0A8V8TKQ0, A0A8V8TKR9, V9GZ54, V9HWC0

UniProt curated annotations — full annotation on UniProt →

Function. Ezrin-radixin-moesin (ERM) family protein that connects the actin cytoskeleton to the plasma membrane and thereby regulates the structure and function of specific domains of the cell cortex. Tethers actin filaments by oscillating between a resting and an activated state providing transient interactions between moesin and the actin cytoskeleton. Once phosphorylated on its C-terminal threonine, moesin is activated leading to interaction with F-actin and cytoskeletal rearrangement. These rearrangements regulate many cellular processes, including cell shape determination, membrane transport, and signal transduction. The role of moesin is particularly important in immunity acting on both T and B-cells homeostasis and self-tolerance, regulating lymphocyte egress from lymphoid organs. Modulates phagolysosomal biogenesis in macrophages. Also participates in immunologic synapse formation.

Subunit / interactions. In resting T-cells, part of a PAG1-NHERF1-MSN complex which is disrupted upon TCR activation. Interacts with NHERF1. Interacts with PPP1R16B. Interacts with SELPLG and SYK; these interactions mediate the activation of SYK by SELPLG. Interacts with PDPN (via cytoplasmic domain); this interaction activates RHOA and promotes epithelial-mesenchymal transition. Interacts with SPN/CD43 cytoplasmic tail. Interacts with CD44. Interacts with ICAM2. Interacts with ICAM3 (via C-terminus). Interacts with PDZD8. Interacts with F-actin. Interacts with CD46. Interacts with PTPN6. (Microbial infection) Interacts with HIV-1 envelope protein gp120.

Subcellular location. Cell membrane. Cytoplasm. Cytoskeleton. Apical cell membrane. Cell projection. Microvillus membrane. Microvillus.

Tissue specificity. In all tissues and cultured cells studied.

Post-translational modifications. Phosphorylation on Thr-558 is crucial for the formation of microvilli-like structures. Phosphorylation by ROCK2 suppresses the head-to-tail association of the N-terminal and C-terminal halves resulting in an opened conformation which is capable of actin and membrane-binding. Phosphorylation on Thr-558 by STK10 negatively regulates lymphocyte migration and polarization. S-nitrosylation of Cys-117 is induced by interferon-gamma and oxidatively-modified low-densitity lipoprotein (LDL(ox)) implicating the iNOS-S100A8/9 transnitrosylase complex.

Disease relevance. Immunodeficiency 50 (IMD50) [MIM:300988] A primary immunodeficiency disorder characterized by onset of recurrent bacterial or varicella zoster virus infections in early childhood, profound lymphopenia, hypogammaglobulinemia, fluctuating monocytopenia and neutropenia, and a poor immune response to vaccine antigens. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. A head-to-tail association, of the N-terminal and C-terminal halves results in a closed conformation (inactive form) which is incapable of actin or membrane-binding.

Domain organisation. The [IL]-x-C-x-x-[DE] motif is a proposed target motif for cysteine S-nitrosylation mediated by the iNOS-S100A8/A9 transnitrosylase complex.

RefSeq proteins (2): NP_001427707, NP_002435* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000299	FERM_domain	Domain
IPR000798	Ez/rad/moesin-like	Family
IPR008954	Moesin_tail_sf	Homologous_superfamily
IPR011174	ERM	Family
IPR011259	ERM_C_dom	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR014352	FERM/acyl-CoA-bd_prot_sf	Homologous_superfamily
IPR018979	FERM_N	Domain
IPR018980	FERM_PH-like_C	Domain
IPR019747	FERM_CS	Conserved_site
IPR019748	FERM_central	Domain
IPR019749	Band_41_domain	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR035963	FERM_2	Homologous_superfamily
IPR041789	ERM_FERM_C	Domain
IPR046810	ERM_helical	Domain

Pfam: PF00373, PF00769, PF09379, PF09380, PF20492

UniProt features (66 total): helix 19, strand 15, modified residue 10, mutagenesis site 6, turn 5, region of interest 3, compositionally biased region 3, initiator methionine 1, chain 1, domain 1, sequence variant 1, short sequence motif 1

Structure

Experimental structures (PDB)

10 structures by resolution:

PDB	Title	Method	Resolution (Å)
8CIS	The FERM domain of human moesin with two bound peptides identified by phage display	X-RAY DIFFRACTION	1.52
6TXQ	The high resolution structure of the FERM domain and helical linker of human moesin	X-RAY DIFFRACTION	1.73
8XZ5	SARS-CoV-2 S and moesin complex structure	X-RAY DIFFRACTION	1.8
8CIR	The FERM domain of human moesin with a bound peptide identified by phage display	X-RAY DIFFRACTION	1.85
1EF1	CRYSTAL STRUCTURE OF THE MOESIN FERM DOMAIN/TAIL DOMAIN COMPLEX	X-RAY DIFFRACTION	1.9
6TXS	The structure of the FERM domain and helical linker of human moesin bound to a CD44 …	X-RAY DIFFRACTION	2.2
8CIU	The FERM domain of human moesin mutant H288A	X-RAY DIFFRACTION	2.39
8CIT	The FERM domain of human moesin mutant L281R	X-RAY DIFFRACTION	2.54
1E5W	Structure of isolated FERM domain and first long helix of moesin	X-RAY DIFFRACTION	2.7
1SGH	Moesin FERM domain bound to EBP50 C-terminal peptide	X-RAY DIFFRACTION	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P26038-F1	86.77	0.62

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Mutational cancer driver genes, Disease related genes, Human disease related genes, Primary immunodeficiency

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): plasma membrane

Antibody reliability (HPA): IH enhanced · IF enhanced

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 (10)

Type	Positions
Phosphoserine	74, 407, 527
N6-acetyllysine	79, 139, 165
N6-succinyllysine	83
Phosphotyrosine	116
S-nitrosocysteine	117
Phosphothreonine	558

Mutagenesis-validated functional residues (6)

Position	Phenotype
115	inhibits s-nitrosylation of cys-117; when associated with m-120.
120	inhibits s-nitrosylation of cys-117; when associated with m-115.
556	impairs phosphorylation by stk10.
558	abolishes phosphorylation by stk10.
558	completely abolishes the interaction between n- and c-terminal domains.
558	phosphomimetic mutant.

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 19; 4 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

19 pathways:

ID	Pathway	Evidence
R-HSA-9725370	Signaling by ALK fusions and activated point mutants ⚕	curated
R-HSA-8950505	Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers ⚕	—
R-HSA-9700206	Signaling by ALK in cancer ⚕	—
R-HSA-422475	Axon guidance	—
R-HSA-1280215	Cytokine Signaling in Immune system	—
R-HSA-1266738	Developmental Biology	—
R-HSA-168256	Immune System	—
R-HSA-447115	Interleukin-12 family signaling	—
R-HSA-9020591	Interleukin-12 signaling	—
R-HSA-373760	L1CAM interactions	—
R-HSA-9675108	Nervous system development	—
R-HSA-437239	Recycling pathway of L1	electronic
R-HSA-9709957	Sensory Perception	—
R-HSA-9659379	Sensory processing of sound	—
R-HSA-9662360	Sensory processing of sound by inner hair cells of the cochlea	electronic
R-HSA-9662361	Sensory processing of sound by outer hair cells of the cochlea	electronic
R-HSA-449147	Signaling by Interleukins	—

MSigDB gene sets: 430 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, GSE45365_NK_CELL_VS_CD8A_DC_UP, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GGGACCA_MIR133A_MIR133B, GOBP_ENDOTHELIAL_CELL_DEVELOPMENT, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_MONOPOLAR_CELL_POLARITY, GNF2_MSN, GOBP_GLAND_MORPHOGENESIS, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_REGULATION_OF_PODOSOME_ASSEMBLY, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GCM_MSN, GOBP_EPITHELIAL_CELL_DEVELOPMENT

GO Biological Process (19): immunological synapse formation (GO:0001771), leukocyte cell-cell adhesion (GO:0007159), regulation of cell shape (GO:0008360), regulation of cell size (GO:0008361), positive regulation of gene expression (GO:0010628), gland morphogenesis (GO:0022612), membrane to membrane docking (GO:0022614), T cell proliferation (GO:0042098), establishment of epithelial cell apical/basal polarity (GO:0045198), positive regulation of protein catabolic process (GO:0045732), leukocyte migration (GO:0050900), establishment of endothelial barrier (GO:0061028), T cell aggregation (GO:0070489), T cell migration (GO:0072678), regulation of organelle assembly (GO:1902115), positive regulation of protein localization to early endosome (GO:1902966), regulation of lymphocyte migration (GO:2000401), positive regulation of early endosome to late endosome transport (GO:2000643), cytoskeleton organization (GO:0007010)

GO Molecular Function (9): double-stranded RNA binding (GO:0003725), actin binding (GO:0003779), signaling receptor binding (GO:0005102), structural constituent of cytoskeleton (GO:0005200), enzyme binding (GO:0019899), protein kinase binding (GO:0019901), cell adhesion molecule binding (GO:0050839), protein binding (GO:0005515), cytoskeletal protein binding (GO:0008092)

GO Cellular Component (21): uropod (GO:0001931), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), microvillus (GO:0005902), adherens junction (GO:0005912), focal adhesion (GO:0005925), cell surface (GO:0009986), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), filopodium (GO:0030175), pseudopodium (GO:0031143), microvillus membrane (GO:0031528), vesicle (GO:0031982), apical part of cell (GO:0045177), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), cell periphery (GO:0071944), blood microparticle (GO:0072562)

Reactome top-level categories

14 top-level categories:

Category	Pathways
Sensory processing of sound	2
L1CAM interactions	1
Interleukin-12 signaling	1
Signaling by ALK in cancer	1
Immune System	1
Axon guidance	1
Nervous system development	1
Signaling by Interleukins	1
Cytokine Signaling in Immune system	1
Disease	1
Interleukin-12 family signaling	1
Sensory Perception	1
Developmental Biology	1
Diseases of signal transduction by growth factor receptors and second messengers	1

GO top-level categories

showing 60 of 66 GO namespaces:

Category	Terms
cellular anatomical structure	6
protein binding	4
lymphocyte migration	2
plasma membrane bounded cell projection	2
cytoplasm	2
actin-based cell projection	2
plasma membrane region	2
cell-cell recognition	1
lymphocyte activation	1
cell-cell adhesion	1
regulation of cell morphogenesis	1
regulation of biological quality	1
regulation of cellular component size	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
animal organ morphogenesis	1
gland development	1
membrane docking	1
T cell activation	1
lymphocyte proliferation	1
polarized epithelial cell differentiation	1
establishment of apical/basal cell polarity	1
establishment or maintenance of epithelial cell apical/basal polarity	1
establishment of epithelial cell polarity	1
positive regulation of catabolic process	1
protein catabolic process	1
regulation of protein catabolic process	1
positive regulation of protein metabolic process	1
immune system process	1
cell migration	1
endothelial cell development	1
lymphocyte aggregation	1
regulation of organelle organization	1
regulation of cellular component biogenesis	1
organelle assembly	1
protein localization to early endosome	1
regulation of protein localization to early endosome	1
positive regulation of protein localization to endosome	1
regulation of mononuclear cell migration	1
positive regulation of intracellular transport	1
early endosome to late endosome transport	1
regulation of early endosome to late endosome transport	1
organelle organization	1
RNA binding	1
cytoskeletal protein binding	1
structural molecule activity	1
cytoskeleton	1
cytoskeleton organization	1
kinase binding	1
binding	1
cell trailing edge	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
membrane	1
cell periphery	1
actin filament bundle	1
cell-cell junction	1
cell-substrate junction	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 38 of 50 annotations. The rest are phylogenetic / computational / electronic (IEA).

38 experimentally-supported GO terms:

GO term	NS	Evidence
T cell aggregation	BP	direct assay
T cell migration	BP	direct assay
T cell proliferation	BP	direct assay
establishment of endothelial barrier	BP	genetic interaction
establishment of epithelial cell apical/basal polarity	BP	mutant phenotype
gland morphogenesis	BP	mutant phenotype
immunological synapse formation	BP	direct assay
leukocyte cell-cell adhesion	BP	expression pattern
leukocyte migration	BP	expression pattern
membrane to membrane docking	BP	expression pattern
positive regulation of early endosome to late endosome transport	BP	genetic interaction
positive regulation of gene expression	BP	genetic interaction
positive regulation of protein catabolic process	BP	genetic interaction
positive regulation of protein localization to early endosome	BP	genetic interaction
regulation of cell shape	BP	mutant phenotype
regulation of cell size	BP	mutant phenotype
regulation of lymphocyte migration	BP	mutant phenotype
regulation of organelle assembly	BP	genetic interaction
apical part of cell	CC	direct assay
apical plasma membrane	CC	direct assay
blood microparticle	CC	high-throughput assay
cell periphery	CC	direct assay
cell surface	CC	direct assay
cytoplasm	CC	high-throughput assay
extracellular exosome	CC	high-throughput assay
filopodium	CC	direct assay
focal adhesion	CC	high-throughput assay
microvillus	CC	direct assay
nucleus	CC	high-throughput assay
perinuclear region of cytoplasm	CC	direct assay
plasma membrane	CC	direct assay
pseudopodium	CC	direct assay
vesicle	CC	high-throughput assay
cell adhesion molecule binding	MF	physical interaction
double-stranded RNA binding	MF	direct assay
enzyme binding	MF	physical interaction
protein kinase binding	MF	physical interaction
signaling receptor binding	MF	physical interaction

Protein interactions and networks

STRING

showing 16 of 2,704 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MSN	RDX	P35241	893
MSN	EZR	P15311	892
MSN	NHERF1	O14745	856
MSN	SPN	P16150	731
MSN	ERMN	Q8TAM6	699
MSN	CD44	P16070	691
MSN	NHERF2	Q15599	690
MSN	SLC9A1	P19634	678
MSN	VCL	P18206	664
MSN	RILP	Q96NA2	655
MSN	RHOA	P06749	655
MSN	PPP1R16B	Q96T49	646
MSN	CFL1	P23528	622
MSN	VAV1	P15498	618
MSN	CFL2	Q9Y281	614
MSN	CDC42	P21181	614

IntAct

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

30 partners by confidence:

Partner	Interaction type	MIscore	Records
LRRK2	phosphorylation reaction	0.960	17
EZR	association	0.740	2
NHERF1	physical association	0.680	4
LMO2	physical association	0.560	3
TERF1	physical association	0.510	2
S	physical association	0.500	8
CD44	physical association	0.460	6
L	direct interaction	0.440	3
N	direct interaction	0.440	3
BARD1	direct interaction	0.440	1
M	direct interaction	0.440	1
TTN	direct interaction	0.440	1
KIAA0319L	physical association	0.400	1
CDK11B	physical association	0.370	1
CRB1	physical association	0.370	1
ERBB2	physical association	0.370	1
PCNA	physical association	0.370	1
SYK	association	0.350	2
LAMP2	association	0.350	1
PFDN1	association	0.350	1
SEC31A	association	0.350	1
CDK2	physical association	0.000	1
ELF3	physical association	0.000	1
HLA-B	physical association	0.000	1
HLA-C	physical association	0.000	1
IKBKE	physical association	0.000	1
MYBPC2	physical association	0.000	1
PRKAB1	physical association	0.000	1
SNCG	physical association	0.000	1
TRAF6	physical association	0.000	1

BioGRID (437 interactions; top human partners by supporting records): EZR (Affinity Capture-MS; 23 records), RDX (Proximity Label-MS; 13 records), FBXW2 (Affinity Capture-MS; 5 records), ICAM3 (Affinity Capture-Western; 5 records), TOMM20 (Cross-Linking-MS (XL-MS); 5 records), SKP2 (Affinity Capture-Western; 4 records), VCAM1 (Affinity Capture-Western; 4 records), CD44 (Reconstituted Complex; 3 records), RICTOR (Proximity Label-MS; 3 records), SPN (Affinity Capture-Western; 3 records), ACTB (Proximity Label-MS; 2 records), ARCN1 (Co-fractionation; 2 records), ARHGDIA (Co-fractionation; 2 records), CD274 (Affinity Capture-Western; 2 records), CD81 (Affinity Capture-Western; 2 records)

SIGNOR signaling

showing 8 of 9 signaling interactions:

A	Effect	B	Mechanism
LRRK2	“up-regulates activity”	MSN	phosphorylation
MSN	“form complex”	MSN/PDZD8	binding
STK10	“up-regulates activity”	MSN	phosphorylation
PRKCQ	unknown	MSN	phosphorylation
CDC42BPB	“up-regulates activity”	MSN	phosphorylation
RHOA	“up-regulates activity”	MSN	phosphorylation
MSN	up-regulates	Platelet_aggregation
ROCK1	“up-regulates activity”	MSN	phosphorylation

Protein complexes (CORUM) (3)

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

3 complexes by size:

Complex	Subunits	Members
EZR-MSN-PAG1-RDX-SLC9A3R1 complex	5	MSN, NHERF1, PAG1, RDX, EZR
★ MSN-SELPLG-SYK complex	3	MSN, SELPLG, SYK
MSN-PAG1-SLC9A3R1 complex	3	MSN, NHERF1, PAG1

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 30 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.

GO biological processes:

GO term	Partners	Fold	FDR
protein phosphorylation	5	13.1×	9e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 4 cancer types — BCC, CCRCC, ESCA, ESCC.

intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.

Genetic variants

Variant evidence for MSN: 361 ClinVar records (19 pathogenic / likely pathogenic); 1 GWAS association. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	12
Likely pathogenic	7
Uncertain significance	123
Likely benign	98
Benign	24

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 19 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
372154	NM_002444.3(MSN):c.511C>T (p.Arg171Trp)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
1482598	NM_002444.3(MSN):c.1114del (p.Ala372fs)	Pathogenic	criteria provided, single submitter	1
2017647	NM_002444.3(MSN):c.49G>T (p.Glu17Ter)	Pathogenic	criteria provided, single submitter	1
2019813	NM_002444.3(MSN):c.1174_1183dup (p.Glu395fs)	Pathogenic	criteria provided, single submitter	1
2036029	NM_002444.3(MSN):c.586C>T (p.Gln196Ter)	Pathogenic	criteria provided, single submitter	1
2101770	NM_002444.3(MSN):c.1303C>T (p.Arg435Ter)	Pathogenic	criteria provided, single submitter	1
2729282	NM_002444.3(MSN):c.504G>A (p.Trp168Ter)	Pathogenic	criteria provided, single submitter	1
2758658	NM_002444.3(MSN):c.585_586dup (p.Gln196fs)	Pathogenic	criteria provided, single submitter	1
3639773	NM_002444.3(MSN):c.1471dup (p.Ser491fs)	Pathogenic	criteria provided, single submitter	1
4714962	NM_002444.3(MSN):c.1279C>T (p.Arg427Ter)	Pathogenic	criteria provided, single submitter	1
4803753	NM_002444.3(MSN):c.1348C>T (p.Gln450Ter)	Pathogenic	criteria provided, single submitter	1
2130284	NM_002444.3(MSN):c.13-1G>A	Likely pathogenic	criteria provided, single submitter	9
372155	NM_002444.3(MSN):c.1657C>T (p.Arg553Ter)	Likely pathogenic	criteria provided, single submitter	2
636909	NM_002444.3(MSN):c.1580C>A (p.Ser527Ter)	Likely pathogenic	criteria provided, single submitter	1
804017	NM_002444.3(MSN):c.1601A>C (p.Asp534Ala)	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore MSN’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 41 predictions of 829):

Position(s)	Effect	Δscore	Sites
X:65667854–65667855	donor_loss	1.0000	4
X:65716812	acceptor_gain	1.0000
X:65716816–65716817	acceptor_loss	1.0000	5
X:65716902–65716903	donor_loss	1.0000	5
X:65727812–65727813	acceptor_loss	1.0000	5
X:65727910–65727911	donor_loss	1.0000	5
X:65729713–65729714	donor_loss	1.0000	5
X:65731105–65731106	acceptor_loss	1.0000	6
X:65731191–65731192	donor_loss	1.0000	4
X:65731837	acceptor_gain	1.0000

AlphaMissense

2,088 missense substitutions predicted likely pathogenic (of 3,849 scored), across 456 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
M305	9	0.987	1.000
M200	9	0.968	0.998
M285	9	0.938	0.989
F240	8	0.998	1.000
H288	8	0.998	1.000
F255	8	0.997	1.000
F18	8	0.995	1.000
D542	8	0.995	0.998
D197	8	0.994	0.998
D221	8	0.994	0.999
F269	8	0.993	0.999
N210	8	0.992	0.999
D51	8	0.988	0.998
F206	8	0.988	1.000
D298	8	0.988	0.999
F267	8	0.985	0.999
F45	8	0.980	0.999
F250	8	0.979	1.000
D572	8	0.977	0.995
H179	8	0.976	0.997

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

3 prognostic cancer types:

Cancer	Prognostic	p-value
Glioblastoma Multiforme (validation)	unfavorable	1.26e-05
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	2.34e-05
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000625

Disease associations

OMIM: gene MIM:309845 | disease phenotypes: MIM:300988

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
combined immunodeficiency due to moesin deficiency	Strong	X-linked	4

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
combined immunodeficiency due to moesin deficiency	Definitive	XL

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (2 panels, 2 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

2 panels:

Panel	Rating
COVID-19 research	green
Primary immunodeficiency or monogenic inflammatory bowel disease	green

Mondo (1): combined immunodeficiency due to moesin deficiency (MONDO:0010514)

Orphanet (1): Combined immunodeficiency due to Moesin deficiency (Orphanet:504530)

HPO phenotypes

7 phenotypes (HPO-id order):

HPO	Term
HP:0000010	Recurrent urinary tract infections
HP:0000964	Eczematoid dermatitis
HP:0001419	X-linked recessive inheritance
HP:0001875	Decreased total neutrophil count
HP:0001888	Decreased total lymphocyte count
HP:0002205	Recurrent respiratory infections
HP:0004313	Decreased circulating immunoglobulin concentration

GWAS associations

1 associations:

Study	Trait	p-value
GCST006661_288	Male-pattern baldness	4e-9

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4295733 (SINGLE PROTEIN), CHEMBL5465400 (PROTEIN-PROTEIN INTERACTION)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (2 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

ChEMBL bioactivities

4 potent at pChembl≥5 of 8 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.59	Kd	256.4	nM	CHEMBL5653589
6.59	ED50	256.4	nM	CHEMBL5653589
5.44	IC50	3600	nM	CHEMBL244695
5.00	IC50	1e+04	nM	CHEMBL271690

PubChem BioAssay actives

3 with measured affinity, of 9 total; 3 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148787: Binding affinity to human MSN incubated for 45 mins by Kinobead based pull down assay	kd	0.2565	uM
3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-4,8-dicarboxylic acid	2037711: Inhibition of full-length human GST-tagged MSN/Venus-Flag-tagged CD44 interaction over-expressed in HEK293 cells incubated for 1 hr by chromatography-based GST-pulldown assay	ic50	3.6000	uM
6-carbamoyl-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-4-carboxylic acid	2037711: Inhibition of full-length human GST-tagged MSN/Venus-Flag-tagged CD44 interaction over-expressed in HEK293 cells incubated for 1 hr by chromatography-based GST-pulldown assay	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, decreases methylation, decreases expression	3
sodium arsenite	affects cotreatment, increases abundance, increases expression	3
bisphenol S	increases expression	2
Benzo(a)pyrene	increases expression, increases methylation, decreases methylation	2
Tobacco Smoke Pollution	affects expression, increases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression, decreases expression	1
quercitrin	affects expression	1
arsenite	affects binding, decreases reaction	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
benzo(e)pyrene	increases methylation	1
ferrous chloride	increases expression	1
triphenyltin	increases expression	1
cupric oxide	increases expression	1
tributyltinisothiocyanate	increases expression	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	affects expression	1
tanespimycin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4119031	Binding	Binding affinity to MSN in human NCI-H358 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — *Bioorg Med Chem*

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B9VN	Abcam HeLa MSN KO	Cancer cell line	Female
CVCL_SZ06	HAP1 MSN (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT00211796	Phase 4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	Phase 4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	Phase 4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	Phase 4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	Phase 4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	Phase 4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	Phase 4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	Phase 4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	Phase 4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	Phase 4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	Phase 4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	Phase 4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	Phase 4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	Phase 4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	Phase 4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	Phase 4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	Phase 4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	Phase 4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	Phase 4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	Phase 4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	Phase 4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	Phase 4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	Phase 4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	Phase 4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	Phase 4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	Phase 4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	Phase 4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	Phase 4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	Phase 4	RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT07770152	Phase 4	NOT_YET_RECRUITING	Semaglutide in Youth With Autism Spectrum Disorder
NCT00036231	Phase 3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	Phase 3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	Phase 3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	Phase 3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	Phase 3	COMPLETED	Galantamine Versus Placebo in Childhood Autism
NCT00346736	Phase 3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00352248	Phase 3	COMPLETED	Randomized Controlled Trial of Acupuncture Versus Sham Acupuncture in Autistic Spectrum Disorder
NCT00352352	Phase 3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00355329	Phase 3	COMPLETED	Randomized Control Trial of Using Tongue Acupuncture in Autistic Spectrum Disorder Using PET Scan for Clinical Correlation
NCT00498173	Phase 3	COMPLETED	Effectiveness of Atomoxetine in Treating ADHD Symptoms in Children and Adolescents With Autism
NCT00541346	Phase 3	COMPLETED	A Pilot Study of Daytrana TM in Children With Autism Co-Morbid for Attention Deficit Hyperactivity Disorder (ADHD) Symptoms
NCT00549562	Phase 3	COMPLETED	Study of Paliperidone ER in Adolescents and Young Adults With Autism
NCT00584480	Phase 3	COMPLETED	Pilot Study of the Effect of Hyperbaric Oxygen Treatment on Behavioral and Biomarker Measures in Children With Autism
NCT00655174	Phase 3	COMPLETED	Fluvoxamine and Sertraline in Childhood Autism - Does SSRI Therapy Improve Behaviour and/or Mood?
NCT00881452	Phase 3	COMPLETED	A Trial of CM-AT in Children With Autism
NCT00912691	Phase 3	COMPLETED	A Trial of CM-AT in Children With Autism- Open Label Extension Study
NCT01302964	Phase 3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	Phase 3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01740869	Phase 3	COMPLETED	Autologous Bone Marrow Stem Cells for Children With Autism Spectrum Disorders
NCT01825798	Phase 3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01911442	Phase 3	COMPLETED	Lurasidone Pediatric Autism Study
NCT01914393	Phase 3	COMPLETED	Pediatric Open-Label Extension Study
NCT01972074	Phase 3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02410902	Phase 3	COMPLETED	A Trial of CM-AT in Children With Autism With All Levels of FCT (The Blum Study)
NCT02649959	Phase 3	ACTIVE_NOT_RECRUITING	An Open Label Study of CM-AT for the Treatment of Children With Autism
NCT02654743	Phase 3	COMPLETED	Open Label of Clinical Trial of Sulforaphane in Children With Autism
NCT02985749	Phase 3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	Phase 3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	Phase 3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	Phase 3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for MSN across ~30M SureChEMBL compounds — explore on Sugi Predict.