ECM1

Summary

ECM1 (extracellular matrix protein 1, HGNC:3153) is a protein-coding gene on chromosome 1q21.2, encoding Extracellular matrix protein 1 (Q16610). Involved in endochondral bone formation as negative regulator of bone mineralization.

This gene encodes a soluble protein that is involved in endochondral bone formation, angiogenesis, and tumor biology. It also interacts with a variety of extracellular and structural proteins, contributing to the maintenance of skin integrity and homeostasis. Mutations in this gene are associated with lipoid proteinosis disorder (also known as hyalinosis cutis et mucosae or Urbach-Wiethe disease) that is characterized by generalized thickening of skin, mucosae and certain viscera. Alternatively spliced transcript variants encoding distinct isoforms have been described for this gene.

Source: NCBI Gene 1893 — RefSeq curated summary.

At a glance

• Gene–disease (curated): lipoid proteinosis (Definitive, GenCC)
• GWAS associations: 15
• Clinical variants (ClinVar): 193 total — 22 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 40
• MANE Select transcript: NM_004425

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3153
Approved symbol	ECM1
Name	extracellular matrix protein 1
Location	1q21.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000143369
Ensembl biotype	protein_coding
OMIM	602201
Entrez	1893

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 11 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000346569, ENST00000369047, ENST00000369049, ENST00000470432, ENST00000490346, ENST00000496744, ENST00000498579, ENST00000855845, ENST00000855846, ENST00000855847, ENST00000855848, ENST00000855849, ENST00000855850, ENST00000855851, ENST00000945726

RefSeq mRNA: 3 — MANE Select: NM_004425 NM_001202858, NM_004425, NM_022664

CCDS: CCDS55632, CCDS953, CCDS954

Canonical transcript exons

ENST00000369047 — 10 exons

Exon	Start	End
ENSE00000959621	150509922	150510002
ENSE00001593782	150509661	150509762
ENSE00001636319	150513237	150513789
ENSE00001779686	150511457	150511831
ENSE00001850500	150508109	150508279
ENSE00002180892	150510876	150511198
ENSE00003500975	150512725	150512812
ENSE00003560046	150509531	150509581
ENSE00003569060	150510102	150510182
ENSE00003691809	150512352	150512572

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 99.87.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 87.9363 / max 2736.9496, expressed in 1534 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5108	80.3051	1523
5107	6.2475	1107
5110	1.2397	522
5109	0.1010	35
5111	0.0431	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.87	gold quality
buccal mucosa cell	CL:0002336	99.66	gold quality
pharyngeal mucosa	UBERON:0000355	99.64	gold quality
esophagus mucosa	UBERON:0002469	99.00	gold quality
stromal cell of endometrium	CL:0002255	98.94	gold quality
oral cavity	UBERON:0000167	98.86	gold quality
cauda epididymis	UBERON:0004360	98.79	gold quality
tongue squamous epithelium	UBERON:0006919	97.21	gold quality
gall bladder	UBERON:0002110	97.12	gold quality
amniotic fluid	UBERON:0000173	96.88	gold quality
body of tongue	UBERON:0011876	96.73	gold quality
epithelium of esophagus	UBERON:0001976	96.35	gold quality
corpus epididymis	UBERON:0004359	96.20	gold quality
esophagus squamous epithelium	UBERON:0006920	96.08	gold quality
vagina	UBERON:0000996	95.70	gold quality
periodontal ligament	UBERON:0008266	95.64	gold quality
decidua	UBERON:0002450	95.50	gold quality
right atrium auricular region	UBERON:0006631	95.47	gold quality
tendon of biceps brachii	UBERON:0008188	95.34	gold quality
upper arm skin	UBERON:0004263	95.07	gold quality
cardiac atrium	UBERON:0002081	94.91	gold quality
skin of leg	UBERON:0001511	94.53	gold quality
tongue	UBERON:0001723	93.97	gold quality
vena cava	UBERON:0004087	93.76	gold quality
esophagus	UBERON:0001043	93.73	gold quality
right uterine tube	UBERON:0001302	93.32	gold quality
apex of heart	UBERON:0002098	92.81	gold quality
zone of skin	UBERON:0000014	92.78	gold quality
squamous epithelium	UBERON:0006914	92.68	gold quality
ectocervix	UBERON:0012249	92.26	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-HCAD-1	yes	8683.82
E-MTAB-10287	yes	762.97
E-GEOD-86618	yes	149.78
E-HCAD-11	yes	45.91
E-ANND-3	yes	28.09
E-MTAB-5061	yes	10.99
E-ENAD-27	yes	6.72

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, ESR1, FOXC1, SP1, TFAP2A, TFAP2C

miRNA regulators (miRDB)

13 targeting ECM1, 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-1252-5P	100.00	69.80	2774
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-3659	99.70	67.97	694
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-122B-5P	99.46	70.81	1457
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-767-3P	98.61	67.69	1192
HSA-MIR-4266	98.53	67.29	1035
HSA-MIR-3650	97.88	64.89	693
HSA-MIR-6828-3P	96.06	67.61	1155

Literature-anchored findings (GeneRIF, showing 40)

• Extracellular matrix protein 1 gene (ECM1) mutations in lipoid proteinosis and genotype-phenotype correlation. Seven new homozygous nonsense or frameshift mutations. Exons 6 and 7 most common sites for ECM1 mutations. (PMID:12603844)
• These results indicate that ECM1 tends to be preferentially expressed by metastatic epithelial tumors. (PMID:14550953)
• Frther emphasizes the role of ECM-1 in lipoid proteinosis and highlights unresolved genotype-phenotype correlation in this disease. (PMID:16274456)
• it is reported here that ECM1 interacts with MMP9 and that such interactions diminish the proteolytic activity of MMP9 (PMID:16512877)
• ECM1 played an important role in the growth, metastasis and angiogenesis of laryngeal carcinoma. (PMID:16646403)
• We report here mutation analysis of the ECM1 gene in a Chinese family with lipoid proteinosis. (PMID:17721643)
• This article provides an update on the molecular pathology of lipoid proteinosis, including the addition of 15 new mutations in ECM1 to the mutation database [review] (PMID:17927570)
• ECM1 is a basement membrane protein of the skin (PMID:18200062)
• Single Nucleotide Polymorphism in ECM1 gene is associated with ulcerative colitis (PMID:18438406)
• A survey of ECM1 expression in different tumors indicated that ECM1, although not tumor specific, is significantly elevated in many malignant epithelial tumors that give rise to metastases, emphasizing its relevance in the cancer process. Review. (PMID:18443958)
• ECM1 variation was not associated with Crohn’s disease. (PMID:19068216)
• ECM proteins such as EDBFN and collagen are upregulated in ERM and PDR, and are regulated by TGF-beta. (PMID:19219685)
• Functional and structural characterisation of human colostrum free secretory component. (PMID:19230975)
• ECM1 is a multifunctional binding core and/or a scaffolding protein interacting with a variety of extracellular and structural proteins, contributing to the maintenance of skin integrity and homeostasis. (PMID:19275936)
• A novel homozygous 62-bp insertion in exon 8 of ECM1 in this Pakistani family is a rare mutation affecting both alleles and it may help in further understanding the multifunctional role of ECM1 (PMID:19519837)
• Overexpression of ECM1 is associated with invasive breast carcinomas. (PMID:19521735)
• Identify novel mutations in the human ECM-1 gene in lipoid proteinosis and report lack of genotype-phenotype correlation. (Case report) (PMID:19734986)
• The ECM/SULF1 and ECM/COLLAGEN metagenes showed inconsistent association with DMFS in the three prognostic data sets in both breast neoplasm subtypes, and the combined P values were not significant. (PMID:20805453)
• PLSCR1 interacts with the tandem repeat region of ECM1a in the dermal epidermal junction zone of human skin. (PMID:20870722)
• The expression of ECM1 was found to be an independent factor for predicting overall and disease-free survival of hepatocellular carcinoma. (PMID:21128013)
• neurologic and neuroradiologic characteristics and ECM1 gene mutations of seven individuals with lipoid proteinosis (LP) from three unrelated consanguineous families (PMID:21349189)
• Case Report: a novel mutation in Pakistani family extends the body of evidence that supports the importance of ECM1 gene for the development of lipoid proteinosis. (PMID:21791056)
• Overexpression of ECM1 contributes to migration and invasion in cholangiocarcinoma. (PMID:22489696)
• Lipoid proteinosis (LP) is a rare autosomal recessive genodermatosis caused by mutations in extracellular matrix protein 1 (ECM1) that involves deposition of basement membrane-like material in the skin and other organs. (PMID:23534907)
• splicing mutation in Chinese lipoid proteinosis family (PMID:23682690)
• Suggest that ECM1 plays promotive roles in the occurrence, development and metastasis of laryngeal carcinoma. (PMID:23696932)
• role for TFAP2C in melanoma via its regulation of ECM1 (PMID:24023917)
• Genetic testing of theECM1 gene showed a homozygous nonsense mutation c.1441C > T (p.Arg481X) in exon 10, confirming the diagnosis of lipoid proteinosis. (PMID:24079542)
• Clinical assays for ECM1 and TEX101 have the potential to replace most of the diagnostic testicular biopsies and facilitate the prediction of outcome of sperm retrieval procedures, increasing the reliability and success of assisted reproduction techniques (PMID:24259048)
• The data supports the conclusion that the c.742G>T mutation nonsense mutation in ECM1 is the pathological cause of lipoid proteinosis. (PMID:24413997)
• homozygous missense mutation p.C220G of ECM1 was identified by Sanger sequencing, which is a major allele in Chinese patients with LP (PMID:24708644)
• High extracellular matrix protein 1 expression is correlated to carcinogenesis and lymphatic metastasis of gastric cancer (PMID:24779890)
• ECM1 induced the expression of genes that promote the Warburg effect, such as glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA), and hypoxia-inducible factor 1 alpha (HIF-1alpha). (PMID:25446258)
• Report a global loss of 5hmC identified three new genes (ECM1, ATF5, and EOMES) with potential anti-cancer functions that may promote the understanding of the molecular mechanisms of hepatocellular carcinoma development and progression. (PMID:25517360)
• Lipoidproteinosis results from a large homozygous deletion of ECM1 gene in a Chinese family. (PMID:25518807)
• This large cohort revealed extensive phenotypic variability in individuals with the same mutation in ECM1. (PMID:25529926)
• association between beta-catenin and the MUC1 cytoplasmic tail was increased by ECM1 (PMID:25746001)
• MMP-2 protein and ECM1 gene are useful preoperative markers for defining malignancy in suspicious thyroid nodules (PMID:25812648)
• High extracellular matrix protein-1 expression is associated with the growth, metastasis and angiogenesis of laryngeal carcinoma (PMID:25824756)
• Lipoid proteinosis is a rare autosomal recessive disorder caused by mutations in ECM1, encoding extracellular matrix protein 1, a glycoprotein expressed in many organs and which has important protein-protein interactions in tissue homeostasis (PMID:26564090)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ecm1a	ENSDARG00000100535
danio_rerio	ecm1b	ENSDARG00000105239
mus_musculus	Ecm1	ENSMUSG00000028108
rattus_norvegicus	Ecm1	ENSRNOG00000021166

Protein

Protein identifiers

Extracellular matrix protein 1 — Q16610 (reviewed: Q16610)

Alternative names: Secretory component p85

All UniProt accessions (2): Q16610, A0A140VJI7

UniProt curated annotations — full annotation on UniProt →

Function. Involved in endochondral bone formation as negative regulator of bone mineralization. Stimulates the proliferation of endothelial cells and promotes angiogenesis. Inhibits MMP9 proteolytic activity.

Subunit / interactions. Interacts (via C-terminus) with HSPG2 (via C-terminus). Interacts with EFEMP1/FBLN3 and LAMB3. Interacts with MMP9.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Expressed in breast cancer tissues. Little or no expression observed in normal breast tissues. Expressed in skin; wide expression is observed throughout the dermis with minimal expression in the epidermis.

Disease relevance. Lipoid proteinosis (LiP) [MIM:247100] Rare autosomal recessive disorder characterized by generalized thickening of skin, mucosae and certain viscera. Classical features include beaded eyelid papules and laryngeal infiltration leading to hoarseness. Histologically, there is widespread deposition of hyaline material and disruption/reduplication of basement membrane. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. May be due to intron retention.

Isoforms (4)

UniProt ID	Names	Canonical?
Q16610-1	1, 1a	yes
Q16610-2	2, 1b
Q16610-3	3
Q16610-4	4

RefSeq proteins (3): NP_001189787, NP_004416, NP_073155 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008605	ECM1	Family
IPR020858	Serum_albumin-like	Homologous_superfamily

Pfam: PF05782

UniProt features (27 total): splice variant 6, sequence variant 5, region of interest 4, compositionally biased region 3, glycosylation site 3, repeat 2, sequence conflict 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16610-F1	69.05	0.41

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): 354, 444, 530

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation

MSigDB gene sets: 364 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, GOBP_CARTILAGE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOCC_SECRETORY_GRANULE, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_NEGATIVE_REGULATION_OF_HYDROLASE_ACTIVITY, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_POSITIVE_REGULATION_OF_VASCULATURE_DEVELOPMENT, GOBP_GROWTH, DITTMER_PTHLH_TARGETS_UP

GO Biological Process (19): ossification (GO:0001503), angiogenesis (GO:0001525), positive regulation of endothelial cell proliferation (GO:0001938), negative regulation of cytokine-mediated signaling pathway (GO:0001960), chondrocyte development (GO:0002063), regulation of type 2 immune response (GO:0002828), endochondral bone growth (GO:0003416), regulation of transcription by RNA polymerase II (GO:0006357), inflammatory response (GO:0006954), signal transduction (GO:0007165), negative regulation of peptidase activity (GO:0010466), regulation of bone mineralization (GO:0030500), negative regulation of bone mineralization (GO:0030502), biomineral tissue development (GO:0031214), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), positive regulation of angiogenesis (GO:0045766), regulation of T cell migration (GO:2000404), regulation of macromolecule metabolic process (GO:0060255), regulation of primary metabolic process (GO:0080090)

GO Molecular Function (4): protease binding (GO:0002020), interleukin-2 receptor binding (GO:0005134), extracellular matrix structural constituent (GO:0005201), protein binding (GO:0005515)

GO Cellular Component (5): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), extracellular matrix (GO:0031012), platelet dense granule lumen (GO:0031089), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Response to elevated platelet cytosolic Ca2+	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
bone mineralization	2
regulation of metabolic process	2
multicellular organismal process	1
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
endothelial cell proliferation	1
regulation of endothelial cell proliferation	1
positive regulation of epithelial cell proliferation	1
regulation of cytokine-mediated signaling pathway	1
negative regulation of signal transduction	1
cytokine-mediated signaling pathway	1
negative regulation of response to cytokine stimulus	1
chondrocyte differentiation	1
cell development	1
type 2 immune response	1
regulation of immune response	1
bone growth	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
defense response	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
peptidase activity	1
negative regulation of proteolysis	1
negative regulation of hydrolase activity	1
regulation of peptidase activity	1
regulation of ossification	1
regulation of biomineral tissue development	1
negative regulation of ossification	1
regulation of bone mineralization	1
negative regulation of biomineral tissue development	1
tissue development	1
animal organ development	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
angiogenesis	1

Protein interactions and networks

STRING

1530 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ECM1	HSPG2	P98160	784
ECM1	MMP9	P14780	759
ECM1	EFEMP1	Q12805	747
ECM1	IL1RN	P18510	688
ECM1	FN1	P02751	653
ECM1	ITGB4	P16144	626
ECM1	THBS1	P07996	602
ECM1	TIMP1	P01033	582
ECM1	AZGP1	P25311	563
ECM1	VCAN	P13611	544
ECM1	ECM2	O94769	541
ECM1	COMP	P49747	519
ECM1	TIMP3	P35625	517
ECM1	TEX101	Q9BY14	514
ECM1	IGFBP3	P17936	504

IntAct

158 interactions, top by confidence:

A	B	Type	Score
ASH2L	KMT2D	psi-mi:“MI:0914”(association)	0.890
ATF2	BACH1	psi-mi:“MI:0914”(association)	0.780
CCNC	MED19	psi-mi:“MI:0914”(association)	0.640
ALDH3A1	RCCD1	psi-mi:“MI:0914”(association)	0.640
POLR3K	POLR3A	psi-mi:“MI:0914”(association)	0.640
CFAP298	PEX7	psi-mi:“MI:0914”(association)	0.620
DTX2	ECM1	psi-mi:“MI:0915”(physical association)	0.560
ECM1	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
BCAS2	ECM1	psi-mi:“MI:0915”(physical association)	0.560
HOXC8	ECM1	psi-mi:“MI:0915”(physical association)	0.560
FKBP6	ECM1	psi-mi:“MI:0915”(physical association)	0.560
ECM1	ENKD1	psi-mi:“MI:0915”(physical association)	0.560
PRKAR2B	ECM1	psi-mi:“MI:0915”(physical association)	0.560
ECM1	KRTAP9-3	psi-mi:“MI:0915”(physical association)	0.560
FRS3	ECM1	psi-mi:“MI:0915”(physical association)	0.560
FASLG	ECM1	psi-mi:“MI:0915”(physical association)	0.560
GCM2	ECM1	psi-mi:“MI:0915”(physical association)	0.560
LIN7A	ECM1	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	ECM1	psi-mi:“MI:0915”(physical association)	0.560
ECM1	A1CF	psi-mi:“MI:0915”(physical association)	0.560
SNRPC	ECM1	psi-mi:“MI:0915”(physical association)	0.560
ECM1	AIRIM	psi-mi:“MI:0915”(physical association)	0.560
ECM1	SAMD11	psi-mi:“MI:0915”(physical association)	0.560
ECM1	KLHL38	psi-mi:“MI:0915”(physical association)	0.560
LMO4	ECM1	psi-mi:“MI:0915”(physical association)	0.560
ITGB4	ECM1	psi-mi:“MI:0915”(physical association)	0.560
ECM1	GNE	psi-mi:“MI:0915”(physical association)	0.560
GPANK1	ECM1	psi-mi:“MI:0915”(physical association)	0.560
ECM1	DTX2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (147): ECM1 (Affinity Capture-Western), ECM1 (Affinity Capture-MS), ECM1 (Affinity Capture-MS), ECM1 (Affinity Capture-MS), ECM1 (Affinity Capture-MS), ECM1 (Affinity Capture-MS), ECM1 (Affinity Capture-MS), ECM1 (Affinity Capture-MS), ECM1 (Two-hybrid), ECM1 (Affinity Capture-MS), ECM1 (Affinity Capture-MS), ECM1 (Affinity Capture-MS), ECM1 (Affinity Capture-MS), ECM1 (Affinity Capture-MS), ECM1 (Affinity Capture-MS)

ESM2 similar proteins: O08999, O35485, O35806, O43278, O89103, O95428, P13207, P23943, P35054, P49765, P49766, P59383, P97766, P98153, P98154, Q00918, Q14766, Q14767, Q16610, Q28019, Q2Q0I9, Q2TAL6, Q3U515, Q4ZHG4, Q5BIR3, Q5HZW5, Q5NRP8, Q5NRQ0, Q61508, Q61810, Q62894, Q765Z5, Q7TQH7, Q7Z4F1, Q867D0, Q86T13, Q86VZ4, Q8BH27, Q8C8N3, Q8CB67

Diamond homologs: Q16610, Q61508, Q62894

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
TFAP2C	“up-regulates quantity by expression”	ECM1	“transcriptional regulation”
TFAP2A	“up-regulates quantity by expression”	ECM1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	22
Likely pathogenic	8
Uncertain significance	95
Likely benign	19
Benign	28

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1526253	NM_004425.4(ECM1):c.1287_1288del (p.Arg430fs)	Pathogenic
1687218	NM_004425.4(ECM1):c.1209_1210insTAGGAAGCCAATTGATATCATAGCTCAGACCATACCTATGTATCCAAATGGTTCTTTTTTTCC (p.Asn404Ter)	Pathogenic
1802155	NM_004425.4(ECM1):c.1450_1454del (p.Ala484fs)	Pathogenic
1803965	NM_004425.4(ECM1):c.542_543insAACCAAATCTGAA (p.Cys181Ter)	Pathogenic
222945	NM_004425.4(ECM1):c.506dup (p.Gly170fs)	Pathogenic
222947	NM_004425.4(ECM1):c.507del (p.Arg171fs)	Pathogenic
3064070	NM_004425.4(ECM1):c.1304+33_*300del	Pathogenic
3242455	NM_004425.4(ECM1):c.1441C>T (p.Arg481Ter)	Pathogenic
3242456	NM_004425.4(ECM1):c.1305-2A>G	Pathogenic
3242457	NM_004425.4(ECM1):c.735_736del (p.Cys245_Glu246delinsTer)	Pathogenic
3242458	NM_004425.4(ECM1):c.709-2A>G	Pathogenic
3242459	NM_004425.4(ECM1):c.1412_1413dup (p.Leu472fs)	Pathogenic
3242460	NM_004425.4(ECM1):c.826del (p.Gln276fs)	Pathogenic
4078669	NM_004425.4(ECM1):c.1077G>A (p.Trp359Ter)	Pathogenic
4535111	NM_004425.4(ECM1):c.607_613dup (p.Arg205fs)	Pathogenic
4688540	NM_004425.4(ECM1):c.18_22dup (p.Ala8fs)	Pathogenic
587581	NM_004425.4(ECM1):c.1393-1G>T	Pathogenic
7472	NM_004425.4(ECM1):c.1036C>T (p.Gln346Ter)	Pathogenic
7473	NM_004425.4(ECM1):c.1304+35_*302del	Pathogenic
7475	NM_004425.4(ECM1):c.157C>T (p.Arg53Ter)	Pathogenic
7477	NM_004425.4(ECM1):c.480G>A (p.Trp160Ter)	Pathogenic
987237	NM_004425.4(ECM1):c.760C>T (p.Arg254Ter)	Pathogenic
2633555	NM_004425.4(ECM1):c.240_241del (p.Gln81fs)	Likely pathogenic
3064079	NM_004425.4(ECM1):c.1051C>T (p.Gln351Ter)	Likely pathogenic
3362542	NM_004425.4(ECM1):c.49_52del (p.Ala17fs)	Likely pathogenic
3911536	NM_004425.4(ECM1):c.68G>T (p.Gly23Val)	Likely pathogenic
4845807	NM_004425.4(ECM1):c.1392+1G>A	Likely pathogenic
7471	NM_004425.4(ECM1):c.1019del (p.Gln340fs)	Likely pathogenic
7476	NM_004425.4(ECM1):c.499T>A (p.Phe167Ile)	Likely pathogenic
930258	NM_004425.4(ECM1):c.142del (p.Ser48fs)	Likely pathogenic

SpliceAI

2063 predictions. Top by Δscore:

Variant	Effect	Δscore
1:150508275:GGGAG:G	donor_gain	1.0000
1:150508276:GGAG:G	donor_gain	1.0000
1:150508276:GGAGG:G	donor_gain	1.0000
1:150508277:GAG:G	donor_gain	1.0000
1:150508277:GAGG:G	donor_gain	1.0000
1:150508280:G:GA	donor_loss	1.0000
1:150509528:CA:C	acceptor_loss	1.0000
1:150509578:GAAG:G	donor_gain	1.0000
1:150509580:AGGT:A	donor_loss	1.0000
1:150509582:GTAA:G	donor_loss	1.0000
1:150509583:T:G	donor_loss	1.0000
1:150509659:A:AG	acceptor_gain	1.0000
1:150509660:G:GG	acceptor_gain	1.0000
1:150512342:T:TA	acceptor_gain	1.0000
1:150512350:A:AG	acceptor_gain	1.0000
1:150512350:AGT:A	acceptor_gain	1.0000
1:150512350:AGTG:A	acceptor_gain	1.0000
1:150512350:AGTGG:A	acceptor_gain	1.0000
1:150512351:G:GA	acceptor_gain	1.0000
1:150512351:GT:G	acceptor_gain	1.0000
1:150512351:GTG:G	acceptor_gain	1.0000
1:150512351:GTGG:G	acceptor_gain	1.0000
1:150512351:GTGGG:G	acceptor_gain	1.0000
1:150512568:AAGCA:A	donor_gain	1.0000
1:150512569:AGCA:A	donor_gain	1.0000
1:150512570:GCA:G	donor_gain	1.0000
1:150512570:GCAG:G	donor_gain	1.0000
1:150512571:CA:C	donor_gain	1.0000
1:150512573:G:GG	donor_gain	1.0000
1:150512722:T:G	acceptor_gain	1.0000

AlphaMissense

3531 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:150511459:G:C	W237C	0.997
1:150511459:G:T	W237C	0.997
1:150512354:G:C	W362C	0.997
1:150512354:G:T	W362C	0.997
1:150512455:T:G	F396C	0.997
1:150511557:T:G	F270C	0.996
1:150510990:T:G	F167C	0.994
1:150511482:G:A	C245Y	0.993
1:150510989:T:C	F167L	0.992
1:150510991:C:A	F167L	0.992
1:150510991:C:G	F167L	0.992
1:150512376:T:A	C370S	0.992
1:150512377:G:A	C370Y	0.992
1:150512377:G:C	C370S	0.992
1:150511478:T:C	F244L	0.991
1:150511480:C:A	F244L	0.991
1:150511480:C:G	F244L	0.991
1:150511481:T:A	C245S	0.991
1:150511482:G:C	C245S	0.991
1:150511557:T:C	F270S	0.991
1:150512352:T:A	W362R	0.990
1:150512352:T:C	W362R	0.990
1:150512454:T:C	F396L	0.990
1:150512455:T:C	F396S	0.990
1:150512456:T:A	F396L	0.990
1:150512456:T:G	F396L	0.990
1:150511457:T:A	W237R	0.988
1:150511457:T:C	W237R	0.988
1:150511520:T:A	C258S	0.988
1:150511521:G:C	C258S	0.988

dbSNP variants (sampled 300 via entrez): RS1000069549 (1:150510619 G>A), RS1000305569 (1:150513999 T>C), RS1000924743 (1:150512997 A>G), RS1000983602 (1:150506759 A>G,T), RS1001014739 (1:150506538 A>C,G), RS1001361467 (1:150513605 G>A), RS1001413640 (1:150513930 C>T), RS1001570120 (1:150507426 G>A), RS1001967555 (1:150508802 AAAAAGG>A,AAAAAGGAAAAGG), RS1002368895 (1:150512086 C>T), RS1002526066 (1:150512244 C>A,T), RS1002538920 (1:150506481 C>A,T), RS1002996651 (1:150506148 G>A,C), RS1003372230 (1:150510846 C>G,T), RS1003423184 (1:150511207 G>A)

Disease associations

OMIM: gene MIM:602201 | disease phenotypes: MIM:247100, MIM:209850, MIM:209920, MIM:610738, MIM:615285, MIM:616622

GenCC curated gene-disease

Disease	Classification	Inheritance
lipoid proteinosis	Definitive	Autosomal recessive

Mondo (6): lipoid proteinosis (MONDO:0009530), autism (MONDO:0005260), MHC class II deficiency (MONDO:0008855), Kostmann syndrome (MONDO:0012548), congenital neutropenia-myelofibrosis-nephromegaly syndrome (MONDO:0014118), autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency (MONDO:0014710)

Orphanet (5): Lipoid proteinosis (Orphanet:530), Congenital neutropenia-myelofibrosis-nephromegaly syndrome (Orphanet:369852), Mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency (Orphanet:477857), Immunodeficiency by defective expression of MHC class II (Orphanet:572), Kostmann syndrome (Orphanet:99749)

HPO phenotypes

40 total (30 of 40 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000168	Abnormality of the gingiva
HP:0000171	Microglossia
HP:0000179	Thick lower lip vermilion
HP:0000199	Tongue nodules
HP:0000218	High palate
HP:0000718	Aggressive behavior
HP:0000738	Hallucinations
HP:0000962	Hyperkeratosis
HP:0001061	Acne
HP:0001072	Thickened skin
HP:0001250	Seizure
HP:0001332	Dystonia
HP:0001482	Subcutaneous nodule
HP:0001609	Hoarse voice
HP:0002015	Dysphagia
HP:0002121	Generalized non-motor (absence) seizure
HP:0002205	Recurrent respiratory infections
HP:0002232	Patchy alopecia
HP:0002293	Alopecia of scalp
HP:0002354	Memory impairment
HP:0002514	Cerebral calcification
HP:0003577	Congenital onset
HP:0003593	Infantile onset
HP:0005671	Bilateral intracerebral calcifications
HP:0008066	Abnormal blistering of the skin
HP:0011463	Childhood onset
HP:0011830	Abnormal oral mucosa morphology
HP:0011999	Paranoia
HP:0034293	Temporal lobe calcification

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST003720_3	Migraine	1.000000e-08
GCST004946_24	Schizophrenia	5.000000e-09
GCST007201_437	Schizophrenia	1.000000e-07
GCST007201_85	Schizophrenia	1.000000e-08
GCST010002_366	Refractive error	3.000000e-15
GCST010696_11	Cortical thickness (min-P)	2.000000e-23
GCST010697_17	Cortical surface area (min-P)	9.000000e-09
GCST010698_23	Subcortical volume (min-P)	2.000000e-08
GCST010699_48	Brain morphology (min-P)	3.000000e-08
GCST010700_28	Cortical thickness (MOSTest)	8.000000e-38
GCST010701_113	Cortical surface area (MOSTest)	9.000000e-12
GCST010702_126	Subcortical volume (MOSTest)	4.000000e-09
GCST010703_244	Brain morphology (MOSTest)	9.000000e-12
GCST010722_1	Spontaneous coronary artery dissection	3.000000e-16
GCST90000582_7	Spontaneous coronary artery dissection	6.000000e-12

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness
EFO:0010820	spontaneous coronary artery dissection

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D008065	Lipoid Proteinosis of Urbach and Wiethe	C08.618.490.500; C16.320.850.595
C537079	Bare lymphocyte syndrome 2 (supp.)
C537592	Neutropenia, Severe Congenital, Autosomal Recessive 3 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	3
Doxorubicin	increases expression	2
Estradiol	decreases expression, affects cotreatment, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Cadmium Chloride	increases expression	2
aristolochic acid I	decreases expression	1
propionaldehyde	increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
deoxynivalenol	decreases expression	1
lead acetate	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
beta-lapachone	increases expression	1
butyraldehyde	increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
cupric chloride	increases expression	1
nickel sulfate	increases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
2-palmitoylglycerol	increases expression	1
3-nitrobenzanthrone	affects expression	1
monomethylarsonous acid	increases expression	1
nutlin 3	affects cotreatment, increases expression	1
incobotulinumtoxinA	increases expression	1
NSC 689534	increases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	increases expression	1
Arsenic Trioxide	increases expression	1
Benzo(a)pyrene	increases methylation	1
Benzoates	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D8KL	Ubigene HCT 116 ECM1 KO	Cancer cell line	Male
CVCL_E1KQ	HyCyte HeLa KO-hECM1	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism
NCT00346736	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00352248	PHASE3	COMPLETED	Randomized Controlled Trial of Acupuncture Versus Sham Acupuncture in Autistic Spectrum Disorder
NCT00352352	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00355329	PHASE3	COMPLETED	Randomized Control Trial of Using Tongue Acupuncture in Autistic Spectrum Disorder Using PET Scan for Clinical Correlation
NCT00498173	PHASE3	COMPLETED	Effectiveness of Atomoxetine in Treating ADHD Symptoms in Children and Adolescents With Autism
NCT00541346	PHASE3	COMPLETED	A Pilot Study of Daytrana TM in Children With Autism Co-Morbid for Attention Deficit Hyperactivity Disorder (ADHD) Symptoms