KREMEN1

kringle containing transmembrane protein 1

Basic information

Region (hg38): 22:29073035-29168333

Previous symbols: [ "KREMEN" ]

Links

ENSG00000183762

∙ ∙ OMIM:609898 ∙ HGNC:17550 ∙ Uniprot:Q96MU8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

ectodermal dysplasia 13, hair/tooth type (Moderate), mode of inheritance: AR
ectodermal dysplasia 13, hair/tooth type (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ectodermal dysplasia 13, hair/tooth type	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Dental; Dermatologic	27049303

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KREMEN1 gene.

Inborn_genetic_diseases (68 variants)
not_provided (35 variants)
Ectodermal_dysplasia_13,_hair/tooth_type (7 variants)
KREMEN1-related_disorder (2 variants)
Infantile_cerebellar-retinal_degeneration (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KREMEN1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001039570.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				9 clinvar	6 clinvar	15
missense	1 clinvar		65 clinvar	8 clinvar	2 clinvar	76
nonsense			1 clinvar			1
start loss						0
frameshift	1 clinvar		2 clinvar			3
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	2	0	70	17	8

Highest pathogenic variant AF is 0.0000065664194

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KREMEN1	protein_coding	protein_coding	ENST00000327813	10	95256

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0114	0.987	124772	0	37	124809	0.000148

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.778	239	275	0.868	0.0000159	3191
Missense in Polyphen		98	115.43	0.84898		1331
Synonymous	0.702	98	107	0.914	0.00000700	977
Loss of Function	2.76	7	20.5	0.342	8.67e-7	257

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000226	0.000223
Ashkenazi Jewish	0.00	0.00
East Asian	0.000890	0.000890
Finnish	0.00	0.00
European (Non-Finnish)	0.000142	0.000141
Middle Eastern	0.000890	0.000890
South Asian	0.0000329	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: 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. In the absence of DKK1, potentiates Wnt-beta-catenin signaling by maintaining LRP5 or LRP6 at the cell membrane. Can trigger apoptosis in a Wnt-independent manner and this apoptotic activity is inhibited upon binding of the ligand DKK1. Plays a role in limb development; attenuates Wnt signaling in the developing limb to allow normal limb patterning and can also negatively regulate bone formation. Modulates cell fate decisions in the developing cochlea with an inhibitory role in hair cell fate specification. {ECO:0000250|UniProtKB:Q90Y90, ECO:0000250|UniProtKB:Q99N43}.;
Disease: DISEASE: Ectodermal dysplasia 13, hair/tooth type (ECTD13) [MIM:617392]: A form of ectodermal dysplasia, a disorder due to abnormal development of two or more ectodermal structures. ECTD13 is an autosomal recessive form characterized by severe oligodontia accompanied by anomalies of hair and skin. {ECO:0000269|PubMed:27049303}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: WNT-Ncore;Wnt Signaling Pathway;Signaling by WNT;Signal Transduction;Negative regulation of TCF-dependent signaling by WNT ligand antagonists;Wnt;Wnt Canonical;Wnt signaling network;TCF dependent signaling in response to WNT;Wnt Mammals (Consensus)

Recessive Scores

pRec: 0.135

Intolerance Scores

loftool: 0.554
rvis_EVS: 0.4
rvis_percentile_EVS: 76.36

Haploinsufficiency Scores

pHI: 0.246
hipred: Y
hipred_score: 0.738
ghis: 0.511

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: S
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.486

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Kremen1
Phenotype: limbs/digits/tail phenotype; normal phenotype; skeleton phenotype;

Zebrafish Information Network

Gene name: kremen1
Affected structure: hair cell
Phenotype tag: abnormal
Phenotype quality: has extra parts of type

Gene ontology

Biological process: apoptotic process;cell communication;Wnt signaling pathway;negative regulation of ossification;limb development;regulation of canonical Wnt signaling pathway;negative regulation of canonical Wnt signaling pathway
Cellular component: plasma membrane;membrane;integral component of membrane
Molecular function: protein binding