SFRP1

protein-coding

secreted frizzled related protein 1, the group of MicroRNA protein coding host genes|Secreted frizzled-related proteins

Gene summary

This gene encodes a member of the SFRP family that contains a cysteine-rich domain homologous to the putative Wnt-binding site of Frizzled proteins. Members of this family act as soluble modulators of Wnt signaling; epigenetic silencing of SFRP genes leads to deregulated activation of the Wnt-pathway which is associated with cancer. This gene may also be involved in determining the polarity of photoreceptor cells in the retina. [provided by RefSeq, Sep 2009]

MANE transcript

NM_003012.5

Inheritance

—

ClinVar variants

U:28B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr8:41,261,962-41,309,473

External References & Databases

Ensembl (ENSG00000104332)

Transcript & Mutation Effects

hg38 • Region Span ~47.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SFRP1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 27

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003012.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar		2 clinvar	3
missense			27 clinvar	1 clinvar		28
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	28	1	2	31

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003012.5	RefSeq	NP_003003.3	3	MANE Select
ENST00000220772.8	Ensembl	ENSP00000220772.3	3	MANE Select
ENST00000379845.3	Ensembl	ENSP00000369174.3	3	Standard
ENST00000379845.4	Ensembl	ENSP00000369174.3	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Wnt signaling pathway - Homo sapiens (human)
WNT-Ncore
Endoderm Differentiation
Vitamin D Receptor Pathway
BMP2-WNT4-FOXO1 Pathway in Human Primary Endometrial Stromal Cell Differentiation

Biological Process

osteoblast differentiation
ureteric bud development
positive regulation of cell-matrix adhesion
hematopoietic progenitor cell differentiation
proteolysis

Molecular Function

cysteine-type endopeptidase activity
frizzled binding
protein binding
drug binding
heparin binding

Cellular Component

extracellular region
extracellular space
cytosol
plasma membrane
cell surface

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000220772
Coding exons: 3
Length: 47536
Individuals with no LoFs: 125738
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 125740
p: 0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.31	127	176	0.722	0.00000824	2065
Missense (PolyPhen)		34	67.779	0.50163		789
Synonymous	-0.934	87	76.6	1.14	0.00000397	583
Loss of Function	2.99	0	10.4	0.00	4.40e-7	128

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0.000066	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Soluble frizzled-related proteins (sFRPS) function as modulators of Wnt signaling through direct interaction with Wnts. They have a role in regulating cell growth and differentiation in specific cell types. SFRP1 decreases intracellular beta-catenin levels (By similarity). Has antiproliferative effects on vascular cells, in vitro and in vivo, and can induce, in vivo, an angiogenic response. In vascular cell cycle, delays the G1 phase and entry into the S phase (By similarity). In kidney development, inhibits tubule formation and bud growth in metanephroi (By similarity). Inhibits WNT1/WNT4-mediated TCF-dependent transcription. {ECO:0000250}.;

Recessive Scores

pRec: 0.422

Intolerance Scores

LoFtool: 0.0932
RVIS EVS: -0.47
RVIS percentile EVS: 23.04

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.981

Gene Damage Prediction

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