MSR1

Chr 8

macrophage scavenger receptor 1

Also known as: CD204, SCARA1, SR-A, SR-AI, SR-AII, SR-AIII, SRA, phSR1

NCBI Gene: 4481 ENSG00000038945 UniProt: P21757 OMIM: 153622

This gene encodes class A macrophage scavenger receptors that mediate endocytosis of modified low-density lipoproteins and other macromolecules in macrophages. Mutations are associated with Barrett esophagus and esophageal adenocarcinoma with autosomal dominant inheritance. The gene shows low constraint to loss-of-function variants, suggesting haploinsufficiency may not be the primary disease mechanism.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes the class A macrophage scavenger receptors, which include three different types (1, 2, 3) generated by alternative splicing of this gene. These receptors or isoforms are macrophage-specific trimeric integral membrane glycoproteins and have been implicated in many macrophage-associated physiological and pathological processes including atherosclerosis, Alzheimer's disease, and host defense. The isoforms type 1 and type 2 are functional receptors and are able to mediate the endocytosis of modified low density lipoproteins (LDLs). The isoform type 3 does not internalize modified LDL (acetyl-LDL) despite having the domain shown to mediate this function in the types 1 and 2 isoforms. It has an altered intracellular processing and is trapped within the endoplasmic reticulum, making it unable to perform endocytosis. The isoform type 3 can inhibit the function of isoforms type 1 and type 2 when co-expressed, indicating a dominant negative effect and suggesting a mechanism for regulation of scavenger receptor activity in macrophages. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Barrett esophagus/esophageal adenocarcinomaMIM #614266

UniProtProstate cancer

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Barrett esophagus/esophageal adenocarcinoma; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.70

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.70LOEUF

pLI 0.000

Z-score -1.05

OE 1.24 (0.92–1.70)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-2.07Z-score

OE missense 1.37 (1.25–1.50)

341 obs / 249.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.24 (0.92–1.70)

0≤0.351.4

Missense OE?1.37 (1.25–1.50)

0≤0.61.4

Synonymous OE?1.19

0≤1.21.6

LoF obs/exp: 27 / 21.7Missense obs/exp: 341 / 249.1Syn Z: -1.43

Background carrier burden — how many people carry a rare variant somewhere in MSR1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 59

933 rare PASS variants

Rare truncating (LoF)

1 in 350

117 rare PASS variants

Rare synonymous (reference)

1 in 120

275 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MSR1. 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 82	1 in 380
South Asian	~43k	1 in 61	1 in 290
Remaining (unassigned)	~30k	1 in 52	1 in 670
European (Finnish)	~27k	1 in 210	≈ 1 in 27,000
Admixed American	~22k	1 in 59	1 in 350
African / African American	~21k	1 in 55	1 in 420
East Asian	~20k	1 in 79	1 in 1,200
Ashkenazi Jewish	~13k	1 in 160	≈ 1 in 4,300
Middle Eastern	~2,884	1 in 55	≈ 1 in 580

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): 8 of 9 coding exons well covered in gnomAD exomes; exon 7 marginal. Genomes: 7 of 9 (exons 7, 9 below).? see exons ↓