KREMEN2 (kringle containing transmembrane protein 2)

Gene

• Entrez ID: 79412
• Gene name: Kringle containing transmembrane protein 2
• Gene symbol: KREMEN2
• Synonyms (NCBI Gene): KRM2
• Chromosome: 16
• Chromosome location: 16p13.3
• Summary: This gene encodes a high-affinity dickkopf homolog 1 (DKK1) transmembrane receptor. A similar protein in mouse functions interacts with with DKK1 to block wingless (WNT)/beta-catenin signaling. The encoded protein forms a ternary membrane complex with DKK

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT004564	hsa-miR-29a-3p	Luciferase reporter assay, qRT-PCR, Western blot	20551325
MIRT030146	hsa-miR-26b-5p	Microarray	19088304
MIRT1100846	hsa-miR-1254	CLIP-seq
MIRT1100847	hsa-miR-185	CLIP-seq
MIRT1100848	hsa-miR-2861	CLIP-seq
MIRT1100849	hsa-miR-3116	CLIP-seq
MIRT1100850	hsa-miR-3619-3p	CLIP-seq
MIRT1100851	hsa-miR-3690	CLIP-seq
MIRT1100852	hsa-miR-4306	CLIP-seq
MIRT1100853	hsa-miR-4512	CLIP-seq
MIRT1100854	hsa-miR-4644	CLIP-seq
MIRT1100855	hsa-miR-4776-5p	CLIP-seq
MIRT2027487	hsa-miR-361-3p	CLIP-seq
MIRT2258798	hsa-miR-3661	CLIP-seq
MIRT2258799	hsa-miR-631	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004888	Function	Transmembrane signaling receptor activity	IBA
GO:0005886	Component	Plasma membrane	IBA
GO:0005886	Component	Plasma membrane	TAS
GO:0007165	Process	Signal transduction	IBA
GO:0016020	Component	Membrane	IEA
GO:0016055	Process	Wnt signaling pathway	IEA
GO:0030279	Process	Negative regulation of ossification	IEA
GO:0030279	Process	Negative regulation of ossification	ISS
GO:0031901	Component	Early endosome membrane	TAS
GO:0060173	Process	Limb development	IEA
GO:0060173	Process	Limb development	ISS

Other IDs

• MIM: 609899
• HGNC: 18797
• e!Ensembl: ENSG00000131650

Protein

• UniProt ID: Q8NCW0
• Protein name: Kremen protein 2 (Dickkopf receptor 2) (Kringle domain-containing transmembrane protein 2) (Kringle-containing protein marking the eye and the nose)
• Protein function: Receptor for Dickkopf proteins. Cooperates with DKK1/2 to inhibit Wnt/beta-catenin signaling by promoting the endocytosis of Wnt receptors LRP5 and LRP6. Plays a role in limb development; attenuates Wnt signaling in the developing limb to allow
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00051	Kringle	36 → 119	Kringle domain	Domain
  PF01822	WSC	124 → 205	WSC domain	Domain
  PF00431	CUB	219 → 323	CUB domain	Domain

• Sequence:

  MGTQALQGFLFLLFLPLLQPRGASAGSLHSPGLSECFQVNGADYRGHQNRTGPRGAGRPC
  LFWDQTQQHSYSSASDPHGRWGLGAHNFCRNPDGDVQPWCYVAETEEGIYWRYCDIPSCH
  MPGYLGCFVDSGAPPALSGPSGTSTKLTVQVCLRFCRMKGYQLAGVEAGYACFCGSESDL
  ARGRLAPATDCDQICFGHPGQLCGGDGRLGVYEVSVGSCQGNWTAPQGVIYSPDFPDEYG
  PDRNCSWALGPPGAALELTFRLFELADPRDRLELRDAASGSLLRAFDGARPPPSGPLRLG
  TAALLLTFRSDARGHAQGFALTYRGLQDAAEDPEAPEGSAQTPAAPLDGANVSCSPRPGA
  PPAAIGARVFSTVTAVSVLLLLLLGLLRPLRRRSCLLAPGKGPPALGASRGPRRSWAVWY
  QQPRGVALPCSPGDPQAEGSAAGYRPLSASSQSSLRSLISAL

• Sequence length: 462

Pathways

Reactome:

Negative regulation of TCF-dependent signaling by WNT ligand antagonists
Misspliced LRP5 mutants have enhanced beta-catenin-dependent signaling

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ANDROGENETIC ALOPECIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ependymoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Cardiovascular Diseases	Cardiovascular disease	Pubtator	30813608	Associate	★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	37123533	Stimulate	★☆☆☆☆ Found in Text Mining only
Depressive disorder	Mental Depression	BEFREE	30640180		★☆☆☆☆ Found in Text Mining only
Gastrointestinal Neoplasms	Gastrointestinal neoplasm	Pubtator	18461655	Inhibit	★☆☆☆☆ Found in Text Mining only
Lymphatic Metastasis	Lymphatic metastasis	Pubtator	37123533	Stimulate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of gastrointestinal tract	Malignant gastrointestinal tract tumors	BEFREE	18461655		★☆☆☆☆ Found in Text Mining only
Mental Depression	Mental Depression	BEFREE	30640180		★☆☆☆☆ Found in Text Mining only
Multiple Myeloma	Multiple myeloma	Pubtator	20846389	Associate	★☆☆☆☆ Found in Text Mining only
Osteolysis	Osteolysis	Pubtator	25399506	Associate	★☆☆☆☆ Found in Text Mining only
Osteoporosis	Osteoporosis	BEFREE	28487939		★☆☆☆☆ Found in Text Mining only