SCARF2

Chr 22AR

scavenger receptor class F member 2

Also known as: NSR1, SREC-II, SREC2, SRECRP-1, VDEGS

NCBI Gene: 91179ENSG00000244486UniProt: Q96GP6

The protein encoded by this gene is similar to SCARF1/SREC-I, a scavenger receptor protein that mediates the binding and degradation of acetylated low density lipoprotein (Ac-LDL). This protein has only little activity of internalizing modified low density lipoproteins (LDL), but it can interact with SCARF1 through its extracellular domain. The association of this protein with SCARF1 is suppressed by the presence of scavenger ligands. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Van den Ende-Gupta syndromeMIM #600920
AR
667
ClinVar variants
215
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— SCARF2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
215 Pathogenic / Likely Pathogenic· 186 VUS of 667 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.19LOEUF
pLI 1.000
Z-score 5.01
OE 0.06 (0.02–0.19)
Highly constrained

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

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
3.02Z-score
OE missense 0.62 (0.56–0.68)
305 obs / 493.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.06 (0.02–0.19)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.62 (0.56–0.68)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.79
0≤1.21.6
LoF obs/exp: 2 / 33.1Missense obs/exp: 305 / 493.6Syn Z: 2.55

ClinVar Variant Classifications

667 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic201
Likely Pathogenic14
VUS186
Likely Benign46
Benign42
Conflicting4
201
Pathogenic
14
Likely Pathogenic
186
VUS
46
Likely Benign
42
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
1
199
0
201
Likely Pathogenic
2
1
11
0
14
VUS
4
154
26
2
186
Likely Benign
0
5
11
30
46
Benign
3
5
27
7
42
Conflicting
—4
Total1016627439493

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SCARF2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

SCARF2-related Van den Ende-Gupta syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Van den Ende-Gupta syndrome

MIM #600920

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Results of next-generation sequencing gene panel diagnostics including copy-number variation analysis in 810 patients suspected of heritable thoracic aortic disorders.
Overwater E et al.·Hum Mutat
2018Cohort
Identification of a novel variant of SCARF2 in a Jordanian family with a van den Ende-Gupta Syndrome and literature review.
Odeh O et al.·Clin Dysmorphol
2022Review
Analysis of CRSsNP Proteome Using a Highly Multiplexed Approach in Nasal Mucus.
Pesold VV et al.·Am J Rhinol Allergy
2023Review
Sclerocornea in a patient with van den Ende-Gupta syndrome homozygous for a SCARF2 microdeletion.
Migliavacca MP et al.·Am J Med Genet A
2014
Two novel variants in SCARF2 gene underlie van den Ende-Gupta syndrome.
Karaer D et al.·Am J Med Genet A
2022Case report
Integration of genetic, transcriptomic, and clinical data provides insight into 16p11.2 and 22q11.2 CNV genes.
Vysotskiy M et al.·Genome Med
2021
Combining Algorithms to Find Signatures That Predict Risk in Early-Stage Stomach Cancer.
Nation JB et al.·J Comput Biol
2021
Further delineation of van den Ende-Gupta syndrome: Genetic heterogeneity and overlap with congenital heart defects and skeletal malformations syndrome.
Hildebrandt CC et al.·Am J Med Genet A
2021Case report
First Prenatal Case of Genotypically and Phenotypically Overlapping Double Molecular Diagnosis of Van den Ende-Gupta and 22q11.2 Deletion Syndromes.
Racine C et al.·Mol Genet Genomic Med
2025Case report
Molecular Characterization of Three Canine Models of Human Rare Bone Diseases: Caffey, van den Ende-Gupta, and Raine Syndromes.
Hytönen MK et al.·PLoS Genet
2016Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools