ECM2

Summary

ECM2 (extracellular matrix protein 2, HGNC:3154) is a protein-coding gene on chromosome 9q22.31, encoding Extracellular matrix protein 2 (O94769). Promotes matrix assembly and cell adhesiveness.

ECM2 encodes extracellular matrix protein 2, so named because it shares extensive similarity with known extracelluar matrix proteins. Three transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 1842 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 12 total
• MANE Select transcript: NM_001393

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3154
Approved symbol	ECM2
Name	extracellular matrix protein 2
Location	9q22.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000106823
Ensembl biotype	protein_coding
OMIM	603479
Entrez	1842

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 12 protein_coding

ENST00000344604, ENST00000375540, ENST00000395534, ENST00000444490, ENST00000864385, ENST00000864386, ENST00000864387, ENST00000864388, ENST00000864389, ENST00000864390, ENST00000864391, ENST00000970619

RefSeq mRNA: 3 — MANE Select: NM_001393 NM_001197295, NM_001197296, NM_001393

CCDS: CCDS56578, CCDS6698

Canonical transcript exons

ENST00000344604 — 10 exons

Exon	Start	End
ENSE00000711485	92500727	92501053
ENSE00000711487	92502513	92502652
ENSE00000711491	92505533	92505690
ENSE00000711493	92509899	92510034
ENSE00000711495	92512011	92512126
ENSE00000711497	92514631	92515203
ENSE00000711499	92517687	92517875
ENSE00001467380	92495315	92496483
ENSE00001783126	92522575	92522893
ENSE00003937752	92535933	92535990

Expression profiles

Bgee: expression breadth ubiquitous, 267 present calls, max score 99.50.

FANTOM5 (CAGE): breadth broad, TPM avg 4.9062 / max 271.6544, expressed in 591 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
101435	2.1928	385
101437	0.8814	256
101438	0.5334	226
101433	0.5264	218
101442	0.2695	101
101441	0.1530	63
101436	0.1196	60
101439	0.0848	42
101434	0.0729	34
101440	0.0724	40

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	99.50	gold quality
synovial joint	UBERON:0002217	98.06	gold quality
blood vessel layer	UBERON:0004797	97.85	gold quality
right coronary artery	UBERON:0001625	97.75	gold quality
parietal pleura	UBERON:0002400	97.66	gold quality
skin of hip	UBERON:0001554	97.57	gold quality
tibia	UBERON:0000979	97.50	gold quality
pleura	UBERON:0000977	96.23	gold quality
vena cava	UBERON:0004087	96.15	gold quality
tendon	UBERON:0000043	95.74	gold quality
germinal epithelium of ovary	UBERON:0001304	95.70	gold quality
descending thoracic aorta	UBERON:0002345	95.40	gold quality
thoracic aorta	UBERON:0001515	95.08	gold quality
ascending aorta	UBERON:0001496	95.07	gold quality
layer of synovial tissue	UBERON:0007616	94.94	gold quality
coronary artery	UBERON:0001621	94.79	gold quality
aorta	UBERON:0000947	94.71	gold quality
left coronary artery	UBERON:0001626	94.50	gold quality
popliteal artery	UBERON:0002250	94.43	gold quality
tibial artery	UBERON:0007610	94.43	gold quality
visceral pleura	UBERON:0002401	94.25	gold quality
tendon of biceps brachii	UBERON:0008188	94.14	gold quality
pericardium	UBERON:0002407	94.13	gold quality
adipose tissue	UBERON:0001013	94.10	gold quality
superficial temporal artery	UBERON:0001614	94.08	gold quality
connective tissue	UBERON:0002384	93.91	gold quality
saphenous vein	UBERON:0007318	93.83	gold quality
left ovary	UBERON:0002119	93.71	gold quality
urethra	UBERON:0000057	93.68	gold quality
cauda epididymis	UBERON:0004360	93.68	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	14.46
E-CURD-53	no	93.24

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

73 targeting ECM2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ecm2	ENSMUSG00000043631
rattus_norvegicus	Ecm2	ENSRNOG00000031716

Paralogs (10): EPYC (ENSG00000083782), OGN (ENSG00000106809), FMOD (ENSG00000122176), OMG (ENSG00000126861), OMD (ENSG00000127083), LUM (ENSG00000139329), KERA (ENSG00000139330), PRELP (ENSG00000188783), LINGO4 (ENSG00000213171), LINGO3 (ENSG00000220008)

Protein

Protein identifiers

Extracellular matrix protein 2 — O94769 (reviewed: O94769)

Alternative names: Matrix glycoprotein SC1/ECM2

All UniProt accessions (3): O94769, Q5T9F3, Q5T9F4

UniProt curated annotations — full annotation on UniProt →

Function. Promotes matrix assembly and cell adhesiveness.

Subunit / interactions. Interacts with numerous extracellular matrix proteins. Interacts with MSL1 and RASSF1.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Expressed predominantly in adipose tissue as well as female-specific organs such as mammary gland, ovary, and uterus.

Similarity. Belongs to the small leucine-rich proteoglycan (SLRP) family. SLRP class I subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
O94769-1	1	yes
O94769-2	2

RefSeq proteins (3): NP_001184224, NP_001184225, NP_001384* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001007	VWF_dom	Domain
IPR001611	Leu-rich_rpt	Repeat
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR025875	Leu-rich_rpt_4	Repeat
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR043184	ECM2	Family

Pfam: PF00093, PF12799, PF13855

UniProt features (31 total): repeat 13, compositionally biased region 4, glycosylation site 3, sequence variant 3, domain 2, splice variant 2, signal peptide 1, chain 1, region of interest 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O94769-F1	70.96	0.45

Functional residue map

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

Glycosylation sites (3): 378, 449, 506

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 144 (showing top): MODULE_64, MORF_RAD51L3, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, BROWNE_HCMV_INFECTION_48HR_DN, BLALOCK_ALZHEIMERS_DISEASE_UP, WONG_ENDMETRIUM_CANCER_DN, MODULE_206, MORF_IL4, RIGGI_EWING_SARCOMA_PROGENITOR_DN, TCF11_01, IRF_Q6, GOMF_GLYCOSAMINOGLYCAN_BINDING, GOBP_REGULATION_OF_CELL_SUBSTRATE_ADHESION, MODULE_88, chr9q22

GO Biological Process (3): cell-matrix adhesion (GO:0007160), positive regulation of cell-substrate adhesion (GO:0010811), extracellular matrix organization (GO:0030198)

GO Molecular Function (6): integrin binding (GO:0005178), heparin binding (GO:0008201), collagen V binding (GO:0070052), protein binding (GO:0005515), collagen binding (GO:0005518), protein-containing complex binding (GO:0044877)

GO Cellular Component (3): interstitial matrix (GO:0005614), extracellular matrix (GO:0031012), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell-substrate adhesion	2
protein-containing complex binding	2
binding	2
regulation of cell-substrate adhesion	1
positive regulation of cell adhesion	1
extracellular structure organization	1
external encapsulating structure organization	1
signaling receptor binding	1
cell adhesion molecule binding	1
glycosaminoglycan binding	1
sulfur compound binding	1
collagen binding	1
extracellular matrix	1
external encapsulating structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1102 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ECM2	SNW1	Q13573	805
ECM2	RBM22	Q9NW64	785
ECM2	BUD31	P41223	776
ECM2	CWC15	Q9P013	681
ECM2	CDC5L	Q99459	672
ECM2	PLRG1	O43660	666
ECM2	EFTUD2	Q15029	603
ECM2	ECM1	Q16610	541
ECM2	CWC25	Q9NXE8	514
ECM2	YJU2	Q9BW85	512
ECM2	VWF	P04275	496
ECM2	EPYC	Q99645	465
ECM2	DCN	P07585	445
ECM2	GLT8D2	Q9H1C3	431
ECM2	LUM	P51884	424

IntAct

2 interactions, top by confidence:

A	B	Type	Score
ECM2	FAM20C	psi-mi:“MI:0217”(phosphorylation reaction)	0.440

BioGRID (1): ECM2 (Affinity Capture-MS)

ESM2 similar proteins: A0N0X6, B1H134, B1H234, D3ZAL8, D3ZTV3, F1NUK7, O43155, O94769, O94991, P28653, P58874, P70186, P79119, Q32Q07, Q3MHH9, Q3SXY7, Q504C1, Q5FW85, Q5R482, Q5R6T0, Q5R7M3, Q5RAC4, Q61809, Q6RKD8, Q6UXK5, Q70AK3, Q7TNJ4, Q80ZD9, Q810B7, Q810B8, Q810C0, Q810C1, Q86SJ2, Q86VH5, Q8BGT1, Q8BLU0, Q8BZ81, Q8C110, Q8CBC6, Q8IW52

Diamond homologs: A3KNN3, A4IIW9, A6H789, A6H793, A6NJW4, A8WHP9, E9Q7T7, O46379, O75093, O75094, O88280, O94769, P21793, P24014, P51884, P51885, P51886, P59034, P59035, P83503, Q05443, Q3MHH9, Q5FW85, Q5M7S9, Q65YW8, Q6EMK4, Q6NUI6, Q6R5N8, Q8R5M3, Q8VCH9, Q96PB8, Q9BY71, Q9GKQ6, Q9GZU5, Q9TTE2, Q9WVB4, Q9WVC1, Q9Z0L0, A2ARI4, A4IFA6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	9
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2410 predictions. Top by Δscore:

Variant	Effect	Δscore
9:92500731:T:C	donor_gain	1.0000
9:92502507:ACTT:A	donor_loss	1.0000
9:92502508:CT:C	donor_loss	1.0000
9:92502509:TT:T	donor_loss	1.0000
9:92502510:TA:T	donor_loss	1.0000
9:92502511:A:AC	donor_gain	1.0000
9:92502511:ACT:A	donor_gain	1.0000
9:92502512:C:CT	donor_gain	1.0000
9:92502512:CT:C	donor_gain	1.0000
9:92502512:CTC:C	donor_gain	1.0000
9:92502512:CTCT:C	donor_gain	1.0000
9:92502512:CTCTT:C	donor_gain	1.0000
9:92502650:TTCC:T	acceptor_loss	1.0000
9:92502652:CCTA:C	acceptor_loss	1.0000
9:92502654:T:G	acceptor_loss	1.0000
9:92510035:C:CC	acceptor_gain	1.0000
9:92510036:T:C	acceptor_gain	1.0000
9:92510036:T:TC	acceptor_gain	1.0000
9:92517653:CACA:C	donor_gain	1.0000
9:92517656:A:AC	donor_gain	1.0000
9:92517657:C:CC	donor_gain	1.0000
9:92517672:G:C	donor_gain	1.0000
9:92496479:TGTTC:T	acceptor_gain	0.9900
9:92496482:TCC:T	acceptor_loss	0.9900
9:92496483:CCTAA:C	acceptor_loss	0.9900
9:92496484:C:CC	acceptor_gain	0.9900
9:92496485:T:C	acceptor_loss	0.9900
9:92496540:GAGT:G	donor_gain	0.9900
9:92496543:T:G	donor_gain	0.9900
9:92500720:AATTT:A	donor_loss	0.9900

AlphaMissense

4614 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:92502526:A:G	W531R	0.999
9:92502526:A:T	W531R	0.999
9:92500976:A:G	L561P	0.998
9:92496405:A:C	N670K	0.997
9:92496405:A:T	N670K	0.997
9:92500745:A:G	L638P	0.997
9:92500895:A:G	L588P	0.997
9:92501033:A:G	L542P	0.997
9:92500751:A:G	L636P	0.996
9:92500960:G:C	N566K	0.995
9:92500960:G:T	N566K	0.995
9:92500970:A:G	L563P	0.995
9:92500985:A:C	L558W	0.995
9:92501023:G:C	N545K	0.995
9:92501023:G:T	N545K	0.995
9:92501024:T:A	N545I	0.995
9:92509949:A:G	L419P	0.995
9:92500736:T:A	N641I	0.994
9:92500885:G:C	N591K	0.994
9:92500885:G:T	N591K	0.994
9:92501009:A:T	V550D	0.994
9:92502642:A:G	L492P	0.994
9:92496406:T:A	N670I	0.993
9:92496421:A:G	L665P	0.993
9:92500804:A:C	N618K	0.993
9:92500804:A:T	N618K	0.993
9:92500814:A:G	L615P	0.993
9:92502632:G:C	N495K	0.993
9:92502632:G:T	N495K	0.993
9:92496415:A:G	L667P	0.992

dbSNP variants (sampled 300 via entrez): RS1000035901 (9:92554235 G>C,T), RS1000094805 (9:92501363 C>A,T), RS1000156409 (9:92528134 A>G), RS1000211983 (9:92553872 T>A,C), RS1000265708 (9:92521125 A>G), RS1000274538 (9:92543071 G>A), RS1000278237 (9:92501819 C>T), RS1000302403 (9:92543277 G>A), RS1000376229 (9:92542656 A>G), RS1000456958 (9:92558920 C>T), RS1000513761 (9:92523503 A>G), RS1000568103 (9:92506565 G>A,C,T), RS1000611599 (9:92528563 C>A), RS1000622453 (9:92546480 G>A), RS1000733608 (9:92546591 G>A)

Disease associations

OMIM: gene MIM:603479 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST010725_16	Malaria	9.000000e-06
GCST010725_28	Malaria	6.000000e-06
GCST010725_95	Malaria	6.000000e-06
GCST90020025_1130	Waist-to-hip ratio adjusted for BMI	1.000000e-12
GCST90020027_913	Waist-hip index	3.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	3
Cyclosporine	decreases expression, increases expression	3
Aflatoxin B1	affects expression, decreases expression, increases methylation	3
Formaldehyde	increases expression	2
methyleugenol	decreases expression	1
bisphenol A	affects cotreatment, increases expression	1
methylselenic acid	increases expression	1
hydroquinone	increases expression	1
avobenzone	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
entinostat	decreases expression	1
quinocetone	increases expression	1
bisphenol S	increases expression	1
incobotulinumtoxinA	increases expression	1
NSC 689534	increases expression, affects binding	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	decreases expression	1
Carmustine	increases expression	1
Copper	affects binding, increases expression	1
Dexamethasone	increases expression, affects cotreatment	1
Diethylhexyl Phthalate	decreases expression	1
Doxorubicin	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Nickel	decreases expression	1
Rotenone	decreases expression	1
Selenium	decreases expression	1
Silicon Dioxide	increases expression	1
T-2 Toxin	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	decreases expression	1

Clinical trials (associated diseases)

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