SFRP1

Chr 8

secreted frizzled related protein 1

Also known as: FRP, FRP-1, FRP1, FrzA, SARP2

NCBI Gene: 6422 ENSG00000104332 UniProt: Q8N474 OMIM: 604156

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]

OMIM Research

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

105

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.29

LOEUF· LoF intol.

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.29LOEUF

pLI 0.965

Z-score 2.99

OE 0.00 (0.00–0.29)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

1.31Z-score

OE missense 0.72 (0.62–0.84)

127 obs / 175.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.29)

0≤0.351.4

Missense OE?0.72 (0.62–0.84)

0≤0.61.4

Synonymous OE?1.14

0≤1.21.6

LoF obs/exp: 0 / 10.4Missense obs/exp: 127 / 175.9Syn Z: -0.93

Background carrier burden — how many people carry a rare variant somewhere in SFRP1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 220

436 rare PASS variants

Rare truncating (LoF)

1 in 5,100

37 rare PASS variants

Rare synonymous (reference)

1 in 230

213 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SFRP1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 250	1 in 4,800
South Asian	~43k	1 in 140	1 in 5,400
Remaining (unassigned)	~30k	1 in 180	≈ 1 in 10,000
European (Finnish)	~27k	1 in 490	≈ 1 in 25,000
Admixed American	~22k	1 in 200	≈ 1 in 4,500
African / African American	~21k	1 in 250	≈ 1 in 4,400
East Asian	~20k	1 in 180	1 in 2,300
Ashkenazi Jewish	~13k	1 in 1,100	none seen
Middle Eastern	~2,884	1 in 190	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓