SORL1

Chr 11

sortilin related receptor 1

Also known as: C11orf32, LR11, LRP9, SORLA, SorLA-1, gp250

NCBI Gene: 6653 ENSG00000137642 UniProt: Q92673 OMIM: 602005

This gene encodes a mosaic protein that belongs to at least two families: the vacuolar protein sorting 10 (VPS10) domain-containing receptor family, and the low density lipoprotein receptor (LDLR) family. The encoded protein also contains fibronectin type III repeats and an epidermal growth factor repeat. The encoded preproprotein is proteolytically processed to generate the mature receptor, which likely plays roles in endocytosis and sorting. Mutations in this gene may be associated with Alzheimer's disease. [provided by RefSeq, Feb 2016]

OMIM Research

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtAlzheimer disease

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

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.44

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.44LOEUF

pLI 0.000

Z-score 6.85

OE 0.34 (0.26–0.44)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.03Z-score

OE missense 0.84 (0.80–0.88)

1068 obs / 1271.8 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.34 (0.26–0.44)

0≤0.351.4

Missense OE?0.84 (0.80–0.88)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 42 / 124.5Missense obs/exp: 1068 / 1271.8Syn Z: 0.86

Background carrier burden — how many people carry a rare variant somewhere in SORL1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 21

2,765 rare PASS variants

Rare truncating (LoF)

1 in 540

261 rare PASS variants

Rare synonymous (reference)

1 in 34

1,142 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SORL1. 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 27	1 in 1,200
South Asian	~43k	1 in 18	1 in 740
Remaining (unassigned)	~30k	1 in 18	1 in 620
European (Finnish)	~27k	1 in 52	1 in 1,500
Admixed American	~22k	1 in 21	1 in 1,300
African / African American	~21k	1 in 20	1 in 750
East Asian	~20k	1 in 20	1 in 1,200
Ashkenazi Jewish	~13k	1 in 90	≈ 1 in 4,400
Middle Eastern	~2,884	1 in 21	≈ 1 in 720

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): 38 of 48 coding exons well covered in gnomAD exomes; exons 1, 2, 5, 7, 11 and 5 more marginal. Genomes: all 48.? see exons ↓