MSGN1

Summary

MSGN1 (mesogenin 1, HGNC:14907) is a protein-coding gene on chromosome 2p24.2, encoding Mesogenin-1 (A6NI15). Involved in specifying the paraxial, but not dorsal, mesoderm.

Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in mesoderm formation and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within segment specification and somitogenesis. Predicted to be located in chromatin. Predicted to be active in nucleus.

Source: NCBI Gene 343930 — RefSeq curated summary.

At a glance

• Gene–disease (curated): skeletal dysplasia (Limited, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 38 total
• MANE Select transcript: NM_001105569

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14907
Approved symbol	MSGN1
Name	mesogenin 1
Location	2p24.2
Locus type	gene with protein product
Status	Approved
Aliases	pMesogenin1
Ensembl gene	ENSG00000151379
Ensembl biotype	protein_coding
OMIM	612209
Entrez	343930

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000281047

RefSeq mRNA: 1 — MANE Select: NM_001105569 NM_001105569

CCDS: CCDS42657

Canonical transcript exons

ENST00000281047 — 1 exons

Exon	Start	End
ENSE00000999265	17816460	17817798

Expression profiles

Bgee: expression breadth broad, 16 present calls, max score 69.29.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0977 / max 14.3132, expressed in 41 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
19096	0.0977	41

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bone marrow cell	CL:0002092	69.29	silver quality
colonic epithelium	UBERON:0000397	50.23	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	48.85	gold quality
bone marrow	UBERON:0002371	48.67	silver quality
esophagus mucosa	UBERON:0002469	42.69	gold quality
lower esophagus mucosa	UBERON:0035834	41.42	silver quality
prefrontal cortex	UBERON:0000451	37.97	gold quality
minor salivary gland	UBERON:0001830	37.00	gold quality
skeletal muscle tissue	UBERON:0001134	36.58	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
saliva-secreting gland	UBERON:0001044	36.30	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
right uterine tube	UBERON:0001302	34.49	gold quality
tonsil	UBERON:0002372	34.28	gold quality
adrenal tissue	UBERON:0018303	33.77	gold quality
muscle tissue	UBERON:0002385	33.41	gold quality
esophagus	UBERON:0001043	32.51	silver quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
frontal cortex	UBERON:0001870	31.86	silver quality
liver	UBERON:0002107	31.48	silver quality
sural nerve	UBERON:0015488	30.93	gold quality
uterine cervix	UBERON:0000002	30.16	silver quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
vermiform appendix	UBERON:0001154	29.50	gold quality
lymph node	UBERON:0000029	28.82	gold quality
monocyte	CL:0000576	28.66	gold quality
leukocyte	CL:0000738	28.56	gold quality
ectocervix	UBERON:0012249	28.49	silver quality
duodenum	UBERON:0002114	28.14	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	383.64
E-ANND-3	no	1.15

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
WNT3A

JASPAR motifs

Motif	Name	Family
MA1524.1	MSGN1	Tal-related

JASPAR matrix evidence (PMIDs): PMID:21750544

Upstream regulators (CollecTRI, top): TBX6

Literature-anchored findings (GeneRIF, showing 1)

• Described the cloning, expression and function of the mouse and frog mesogenin 1. (PMID:10837126)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	msgn1	ENSDARG00000070546
mus_musculus	Msgn1	ENSMUSG00000047002
rattus_norvegicus	Msgn1	ENSRNOG00000028518
drosophila_melanogaster	sage	FBGN0037672

Paralogs (2): MESP1 (ENSG00000166823), MESP2 (ENSG00000188095)

Protein

Protein identifiers

Mesogenin-1 — A6NI15 (reviewed: A6NI15)

Alternative names: Paraxial mesoderm-specific mesogenin1, pMesogenin1

All UniProt accessions (1): A6NI15

UniProt curated annotations — full annotation on UniProt →

Function. Involved in specifying the paraxial, but not dorsal, mesoderm. May regulate the expression of T-box transcription factors required for mesoderm formation and differentiation.

Subcellular location. Nucleus.

RefSeq proteins (1): NP_001099039* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011598	bHLH_dom	Domain
IPR036638	HLH_DNA-bd_sf	Homologous_superfamily
IPR040259	Mesogenin/MesP	Family

Pfam: PF00010

UniProt features (6 total): sequence variant 2, chain 1, domain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NI15-F1	68.43	0.33

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-9793380	Formation of paraxial mesoderm
R-HSA-9824272	Somitogenesis
R-HSA-1266738	Developmental Biology
R-HSA-9758941	Gastrulation

MSigDB gene sets: 43 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_FORMATION_OF_PRIMARY_GERM_LAYER, GOBP_ANTERIOR_POSTERIOR_PATTERN_SPECIFICATION, GOBP_SOMITOGENESIS, GOBP_SEGMENTATION, GOBP_GASTRULATION, GOBP_MESODERM_MORPHOGENESIS, GOBP_SEGMENT_SPECIFICATION, GOBP_EMBRYO_DEVELOPMENT, GOBP_MESODERM_DEVELOPMENT, GOBP_SOMITE_DEVELOPMENT, GOBP_TISSUE_MORPHOGENESIS, GOMF_CHROMATIN_BINDING, MARSON_BOUND_BY_FOXP3_UNSTIMULATED

GO Biological Process (6): mesoderm formation (GO:0001707), somitogenesis (GO:0001756), regulation of transcription by RNA polymerase II (GO:0006357), segment specification (GO:0007379), cell differentiation (GO:0030154), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (9): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), chromatin binding (GO:0003682), protein dimerization activity (GO:0046983), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515)

GO Cellular Component (2): chromatin (GO:0000785), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Gastrulation	1
Formation of paraxial mesoderm	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
segmentation	2
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
binding	2
formation of primary germ layer	1
mesoderm morphogenesis	1
anterior/posterior pattern specification	1
chordate embryonic development	1
anatomical structure formation involved in morphogenesis	1
somite development	1
pattern specification process	1
cellular developmental process	1
positive regulation of DNA-templated transcription	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
protein binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

390 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MSGN1	TBX6	O95947	735
MSGN1	RIPPLY2	Q5TAB7	590
MSGN1	MEOX1	P50221	581
MSGN1	UNCX	A6NJT0	521
MSGN1	TCF15	Q12870	454
MSGN1	SMC6	Q96SB8	426
MSGN1	RIPPLY1	Q0D2K3	422
MSGN1	WNT3A	P56704	404
MSGN1	CDX1	P47902	394
MSGN1	CCDC14	Q49A88	388
MSGN1	GEN1	Q17RS7	384
MSGN1	DPCD	Q9BVM2	379
MSGN1	MIXL1	Q9H2W2	379
MSGN1	LFNG	Q8NES3	378
MSGN1	PAX3	P23760	375

IntAct

95 interactions, top by confidence:

A	B	Type	Score
MSGN1	ITGB3BP	psi-mi:“MI:0915”(physical association)	0.560
MSGN1	LDOC1	psi-mi:“MI:0915”(physical association)	0.560
MSGN1	NECAB2	psi-mi:“MI:0915”(physical association)	0.560
MSGN1	AP1B1	psi-mi:“MI:0915”(physical association)	0.560
MSGN1	TCF12	psi-mi:“MI:0915”(physical association)	0.560
MSGN1	MYF5	psi-mi:“MI:0915”(physical association)	0.560
MSGN1	ID1	psi-mi:“MI:0915”(physical association)	0.560
ATP11B	MSGN1	psi-mi:“MI:0915”(physical association)	0.560
MSGN1	MAGEA6	psi-mi:“MI:0915”(physical association)	0.560
MSGN1	TRAF1	psi-mi:“MI:0915”(physical association)	0.560
MSGN1	HAP1	psi-mi:“MI:0915”(physical association)	0.560
MSGN1	EXOC7	psi-mi:“MI:0915”(physical association)	0.560
MSGN1	OST4	psi-mi:“MI:0915”(physical association)	0.560
MSGN1	IGFBP6	psi-mi:“MI:0915”(physical association)	0.560
	MSGN1	psi-mi:“MI:0915”(physical association)	0.560
MSGN1	CCDC172	psi-mi:“MI:0915”(physical association)	0.560
MSGN1	DNALI1	psi-mi:“MI:0915”(physical association)	0.560
MSGN1	CTAG1A	psi-mi:“MI:0915”(physical association)	0.560
MSGN1	BRAT1	psi-mi:“MI:0915”(physical association)	0.560
MSGN1	SERTAD3	psi-mi:“MI:0915”(physical association)	0.560
MSGN1	MYL9	psi-mi:“MI:0915”(physical association)	0.560
MSGN1	ZMYND12	psi-mi:“MI:0915”(physical association)	0.560
MSGN1	ID2	psi-mi:“MI:0915”(physical association)	0.560
MSGN1	ID3	psi-mi:“MI:0915”(physical association)	0.560
MSGN1	ZWINT	psi-mi:“MI:0915”(physical association)	0.560
MSGN1	TCF4	psi-mi:“MI:0915”(physical association)	0.560
MSGN1	TEPSIN	psi-mi:“MI:0915”(physical association)	0.560
MSGN1	TEX12	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (37): MSGN1 (Two-hybrid), MSGN1 (Two-hybrid), MSGN1 (Two-hybrid), MSGN1 (Two-hybrid), MSGN1 (Two-hybrid), MSGN1 (Two-hybrid), MSGN1 (Two-hybrid), MSGN1 (Two-hybrid), MSGN1 (Two-hybrid), MSGN1 (Two-hybrid), MSGN1 (Two-hybrid), MSGN1 (Two-hybrid), MSGN1 (Two-hybrid), MSGN1 (Two-hybrid), MSGN1 (Two-hybrid)

ESM2 similar proteins: A3KNX5, A6NI15, A7YWL5, B0BN13, D3ZLB7, E9Q9M8, O02761, O35906, O70240, O94983, O97930, P01102, P11939, P13346, P23050, P53539, P70298, P70595, P70660, P97303, Q15742, Q28C89, Q3U1J1, Q5EBA3, Q61122, Q61127, Q62722, Q62912, Q62985, Q6NW59, Q80Y50, Q86UZ6, Q8CD60, Q8HZP6, Q90ZL1, Q91ZM2, Q92886, Q96JB3, Q99NA2, Q9BE45

Diamond homologs: A6NI15, O08574, O09105, O42202, P41894, P46581, P48986, P79765, P79766, P79920, P97309, Q08DI0, Q0VG99, Q13562, Q28C89, Q4R5G6, Q60430, Q60867, Q64289, Q90ZL1, Q91616, Q96NK8, Q9BRJ9, Q9DEQ9, Q9HD90, Q9JK54, Q9W690, Q9W6C7, Q9Y4Z2, A8E5T6, O35437, O43680, O60682, O88940, P79782, Q10574, Q20561, Q32PV5, Q5E9S3, Q6GNB7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	36
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

106 predictions. Top by Δscore:

Variant	Effect	Δscore
2:17816605:G:GT	donor_gain	0.8700
2:17816555:G:GT	donor_gain	0.7800
2:17816609:G:GT	donor_gain	0.7000
2:17816797:G:GA	donor_gain	0.6700
2:17816790:TAG:T	donor_gain	0.6300
2:17816791:AGA:A	donor_gain	0.6300
2:17816792:GAG:G	donor_gain	0.6300
2:17817097:G:GG	donor_gain	0.6100
2:17816796:T:TA	donor_gain	0.5700
2:17816926:GA:G	donor_gain	0.5600
2:17817093:GCGC:G	donor_gain	0.5500
2:17817095:GC:G	donor_gain	0.5300
2:17816518:C:T	donor_gain	0.4900
2:17816615:G:T	donor_gain	0.4900
2:17816729:C:T	donor_gain	0.4700
2:17817094:CGC:C	donor_gain	0.4500
2:17817095:GCG:G	donor_gain	0.4500
2:17817092:AGCGC:A	donor_gain	0.4300
2:17817093:GCGCG:G	donor_gain	0.4300
2:17816610:A:T	donor_gain	0.4200
2:17816606:A:T	donor_gain	0.4100
2:17816616:C:T	donor_gain	0.4100
2:17816723:T:G	donor_gain	0.4000
2:17816878:G:GT	donor_gain	0.4000
2:17816679:A:T	donor_gain	0.3800
2:17817036:A:G	donor_gain	0.3800
2:17817037:G:GG	donor_gain	0.3800
2:17816724:G:GG	donor_gain	0.3700
2:17816630:C:G	donor_gain	0.3600
2:17816676:TGG:T	acceptor_gain	0.3600

AlphaMissense

1251 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:17816916:A:T	E133V	1.000
2:17816925:G:T	R136M	1.000
2:17816958:T:A	L147H	1.000
2:17817006:C:T	T163I	1.000
2:17817010:G:C	K164N	1.000
2:17817010:G:T	K164N	1.000
2:17817021:T:A	L168H	1.000
2:17817021:T:C	L168P	1.000
2:17817051:T:C	L178P	1.000
2:17816915:G:A	E133K	0.999
2:17816917:G:C	E133D	0.999
2:17816917:G:T	E133D	0.999
2:17816925:G:C	R136T	0.999
2:17816926:G:C	R136S	0.999
2:17816926:G:T	R136S	0.999
2:17816928:T:C	M137T	0.999
2:17816929:G:A	M137I	0.999
2:17816929:G:C	M137I	0.999
2:17816929:G:T	M137I	0.999
2:17816937:T:C	L140S	0.999
2:17816937:T:G	L140W	0.999
2:17816945:G:C	A143P	0.999
2:17816949:T:C	L144P	0.999
2:17816958:T:C	L147P	0.999
2:17816970:T:C	L151P	0.999
2:17817008:A:C	K164Q	0.999
2:17817008:A:G	K164E	0.999
2:17817012:T:A	I165N	0.999
2:17817012:T:C	I165T	0.999
2:17817012:T:G	I165S	0.999

dbSNP variants (sampled 300 via entrez): RS1002270443 (2:17816114 C>T), RS1002596874 (2:17815907 G>T), RS1003154969 (2:17817910 C>T), RS1003510698 (2:17818193 A>G), RS1003887196 (2:17814842 G>A,C,T), RS1004503766 (2:17815204 C>T), RS1004595252 (2:17816840 G>A,T), RS1004752341 (2:17817198 T>G), RS1006908764 (2:17817696 C>T), RS1006959752 (2:17817335 T>G), RS1008674286 (2:17816244 C>A,T), RS1009170948 (2:17814980 C>T), RS1011276853 (2:17817702 C>T), RS1011641662 (2:17817945 A>G), RS1014093070 (2:17816129 G>A)

Disease associations

OMIM: gene MIM:612209 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
skeletal dysplasia	Limited	Autosomal recessive

Mondo (1): skeletal dysplasia (MONDO:0018230)

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST009391_1171	Metabolite levels	2.000000e-06
GCST009391_1631	Metabolite levels	9.000000e-06
GCST011584_6	Metastatic colorectal cancer survival in treatment with chemotherapy plus biologics	8.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0006524	L-arginine measurement
EFO:0010465	beta-hydroxybutyric acid measurement
EFO:0000714	survival time
EFO:1001480	metastatic colorectal cancer

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	increases reaction, affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases reaction, decreases reaction, increases expression	1
Chir 99021	increases reaction, decreases reaction, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Endosulfan	decreases expression	1
Tretinoin	decreases reaction, increases expression, increases reaction	1
Valproic Acid	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A4F2	SEES3-1V human MSGN1, clone1	Embryonic stem cell	Male
CVCL_A4F3	SEES3-1V human MSGN1, clone2	Embryonic stem cell	Male
CVCL_A4F4	SEES3-1V human MSGN1, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00001754	Not specified	COMPLETED	Study of Skeletal Disorders and Short Stature
NCT02762318	Not specified	TERMINATED	Identification and Characterization of Bone-related Genetic Variants in Families
NCT03548779	Not specified	COMPLETED	North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2
NCT05247645	Not specified	RECRUITING	Data Collection of Patients With Rare Bone Diseases
NCT05876416	Not specified	RECRUITING	Decoding the Genetic Landscape of Skeletal Diseases
NCT05991609	Not specified	ACTIVE_NOT_RECRUITING	Extreme Morphology and Metabolic Health
NCT06002373	Not specified	UNKNOWN	Assessment of Artificial Intelligence for Treatment Decision Recommendation of Adult Skeletal Class III Patients