SCARF1

Chr 17

scavenger receptor class F member 1

Also known as: SREC, SREC-I, SREC1

NCBI Gene: 8578 ENSG00000074660 UniProt: Q14162 OMIM: 607873

The protein is a scavenger receptor expressed in endothelial cells that mediates binding and degradation of acetylated low density lipoprotein and regulates neurite-like outgrowth. Mutations cause Van den Ende-Gupta syndrome, an autosomal recessive disorder characterized by severe contractures, distinctive craniofacial features, and skeletal abnormalities. The gene shows low constraint against loss-of-function variants, consistent with the recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a scavenger receptor that is expressed in endothelial cells. It regulates the uptake of chemically modified low density lipoproteins, including acetylated low density lipoprotein (Ac-LDL), and it may be involved in atherogenesis. This gene is regulated by the transcription factors ZNF444/EZF-2 and SP1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2013]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.73

Clinical Summary— SCARF1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 134 VUS of 164 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.73LOEUF

pLI 0.000

Z-score 2.80

OE 0.48 (0.32–0.73)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.14Z-score

OE missense 0.85 (0.78–0.92)

370 obs / 437.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.48 (0.32–0.73)

0≤0.351.4

Missense OE?0.85 (0.78–0.92)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 16 / 33.5Missense obs/exp: 370 / 437.0Syn Z: -1.01

This gene — mechanism propensity

0.6455th %ile

GOF

0.73top 25%

LOF

0.3356th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

164 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS134

Likely Benign12

Benign2

Pathogenic

134

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	1	0	1
Likely Pathogenic	0	0	0	0	0
VUS	1	132	1	0	134
Likely Benign	0	12	0	0	12
Benign	0	1	0	1	2
Total	1	145	2	1	149

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

View in ClinVar →

86 pathogenic / likely-pathogenic (of 106) ClinVar copy-number / structural variants overlap SCARF1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →