SCARF2

Chr 22AR

scavenger receptor class F member 2

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

NCBI Gene: 91179 ENSG00000244486 UniProt: Q96GP6 OMIM: 613619

SCARF2 encodes an adhesion protein that mediates cell-to-cell interactions and has limited scavenger receptor activity for modified lipoproteins. Biallelic mutations cause Van den Ende-Gupta syndrome, an autosomal recessive disorder characterized by distinctive craniofacial features, skeletal abnormalities, and developmental delays. The gene is highly constrained against loss-of-function variants (pLI 1.0, LOEUF 0.19), indicating intolerance to protein loss.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Van den Ende-Gupta syndromeMIM #600920

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Van den Ende-Gupta syndrome; no ClinGen or GenCC tier

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.19

LOEUF· LoF intol.

LOF

Mechanism· G2P

📖

GeneReview available — SCARF2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

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?

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?

LoF OE?0.06 (0.02–0.19)

0≤0.351.4

Missense OE?0.62 (0.56–0.68)

0≤0.61.4

Synonymous OE?0.79

0≤1.21.6

LoF obs/exp: 2 / 33.1Missense obs/exp: 305 / 493.6Syn Z: 2.55

Background carrier burden — how many people carry a rare variant somewhere in SCARF2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 78

1,248 rare PASS variants

Rare truncating (LoF)

1 in 1,500

118 rare PASS variants

Rare synonymous (reference)

1 in 93

652 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SCARF2. 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 100	1 in 1,900
South Asian	~43k	1 in 41	1 in 1,900
Remaining (unassigned)	~30k	1 in 68	1 in 2,000
European (Finnish)	~27k	1 in 210	1 in 2,300
Admixed American	~22k	1 in 66	1 in 1,600
African / African American	~21k	1 in 48	1 in 1,700
East Asian	~20k	1 in 67	1 in 1,000
Ashkenazi Jewish	~13k	1 in 290	1 in 2,200
Middle Eastern	~2,884	1 in 48	≈ 1 in 1,200

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): 9 of 11 coding exons well covered in gnomAD exomes; exons 1, 11 marginal. Genomes: 10 of 11 (exon 2 below).? see exons ↓