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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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CRIM1
cysteine rich transmembrane BMP regulator 1
Chromosome 2 · 2p22.2
NCBI Gene: 51232Ensembl: ENSG00000150938.11HGNC: HGNC:2359UniProt: Q9NZV1
50PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
PDZ domain bindingnegative regulation of BMP signaling pathwaynegative regulation of osteoblast differentiationnervous system developmentcolobomatous macrophthalmia-microcornea syndromemathematical abilityatrial fibrillationhypertension
✦AI Summary

CRIM1 (cysteine-rich transmembrane BMP regulator 1) is a developmentally regulated transmembrane protein that modulates bone morphogenetic protein (BMP) activity by regulating BMP processing and cell surface delivery 1. The protein contains cysteine-rich repeats and an IGF-binding protein motif 2, enabling interaction with multiple growth factors including TGFβs, BMPs, VEGFs, and PDGFs 3. CRIM1 plays pleiotropic roles during embryogenesis, with expression in notochord, somites, floor plate, and motor neurons during CNS development 2. It regulates organogenesis in the eye, kidney, placenta, and heart 3. CRIM1 haploinsufficiency causes macrophthalmia with microcornea (MACOM) syndrome, an autosomal dominant eye malformation characterized by microcornea, coloboma, and myopia 4. Mouse models demonstrate that reduced Crim1 expression impairs lens epithelial cell development and cell adhesion 5. Beyond ocular development, CRIM1 dysregulation is implicated in multiple pathological conditions. Increased CRIM1 expression occurs in hypoplastic left heart syndrome cardiomyocytes 6, while decreased expression associates with reduced polycystic ovary syndrome risk 7. CRIM1 is also dysregulated in LMNA-associated dilated cardiomyopathy, where it correlates with disease severity 8. Its role in angiogenesis and EMT regulation suggests involvement in cancer progression 1.

Sources cited
1
CRIM1 antagonizes BMPs by regulating their processing and cell surface delivery; involved in angiogenesis and EMT
PMID: 25088037
2
CRIM1 is developmentally regulated, expressed in notochord/motor neurons; contains IGF-binding protein motif and cysteine-rich repeats
PMID: 10642437
3
CRIM1 mediates organogenesis by interacting with TGFβs, BMPs, VEGFs, and PDGFs in eye, kidney, placenta, and heart
PMID: 27044529
4
CRIM1 haploinsufficiency causes MACOM syndrome; mouse models show impaired lens epithelial development
PMID: 25561690
5
CRIM1 deficiency in zebrafish causes reduced eye size and lens defects; associated with dysregulation of fgf1b and clic4
PMID: 40114969
6
CRIM1 expression is increased in cardiomyocytes from hypoplastic left heart syndrome patients
PMID: 35732239
7
CRIM1 decreased expression associates with reduced polycystic ovary syndrome risk; co-expressed in fibroblasts
PMID: 39972362
8
CRIM1 is a dysregulated protein in LMNA-associated dilated cardiomyopathy correlating with disease severity
PMID: 40509996
Disease Associationsⓘ20
colobomatous macrophthalmia-microcornea syndromeOpen Targets
0.46Moderate
mathematical abilityOpen Targets
0.45Moderate
atrial fibrillationOpen Targets
0.45Moderate
hypertensionOpen Targets
0.40Weak
alcohol drinkingOpen Targets
0.37Weak
jaw diseaseOpen Targets
0.32Weak
vein disorderOpen Targets
0.31Weak
lymphatic system diseaseOpen Targets
0.31Weak
cervical carcinomaOpen Targets
0.30Weak
heart failureOpen Targets
0.30Weak
Premature atrial contractionsOpen Targets
0.30Weak
neuroblastomaOpen Targets
0.29Weak
diverticular diseaseOpen Targets
0.26Weak
smoking initiationOpen Targets
0.26Weak
nervous system diseaseOpen Targets
0.25Weak
Abnormality of the skeletal systemOpen Targets
0.23Weak
placenta praeviaOpen Targets
0.21Weak
secondary malignant neoplasmOpen Targets
0.19Weak
HypercholesterolemiaOpen Targets
0.19Weak
Phenotypic abnormalityOpen Targets
0.18Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
FEZ2Protein interaction89%FAUProtein interaction81%VPS41Protein interaction77%TMEM53Shared pathway33%CNTNAP3BShared pathway25%VWC2LShared pathway25%
Tissue Expression6 tissues
Lung
100%
Heart
91%
Brain
52%
Ovary
48%
Liver
15%
Bone Marrow
8%
Gene Interaction Network
Click a node to explore
CRIM1FEZ2FAUVPS41TMEM53CNTNAP3BVWC2L
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q9NZV1
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.38Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.28 [0.21–0.38]
RankingsWhere CRIM1 stands among ~20K protein-coding genes
  • #8,792of 20,598
    Most Researched50
  • #1,789of 17,882
    Most Constrained (LOEUF)0.38 · top quartile
Genes detectedCRIM1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Integrated multi-omic characterization of congenital heart disease.
PMID: 35732239
Nature · 2022
1.00
2
Crim1-, a regulator of developmental organogenesis.
PMID: 27044529
Histol Histopathol · 2016
0.90
3
CRIM1 haploinsufficiency causes defects in eye development in human and mouse.
PMID: 25561690
Hum Mol Genet · 2015
0.80
4
CRIM1, the antagonist of BMPs, is a potential risk factor of cancer.
PMID: 25088037
Curr Cancer Drug Targets · 2014
0.70
5
Polycystic ovary syndrome and epithelial-mesenchymal transition: Mendelian randomization and single-cell analysis insights.
PMID: 39972362
J Ovarian Res · 2025
0.60