ADGRA2

Chr 8

adhesion G protein-coupled receptor A2

Also known as: GPR124, TEM5

NCBI Gene: 25960 ENSG00000020181 UniProt: Q96PE1 OMIM: 606823

Predicted to enable G protein-coupled receptor activity. Involved in canonical Wnt signaling pathway. Located in plasma membrane. Part of Wnt signalosome. [provided by Alliance of Genome Resources, Jun 2026]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.61

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.61LOEUF

pLI 0.000

Z-score 3.75

OE 0.42 (0.30–0.61)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.93Z-score

OE missense 0.80 (0.75–0.86)

612 obs / 762.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.42 (0.30–0.61)

0≤0.351.4

Missense OE?0.80 (0.75–0.86)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 21 / 49.4Missense obs/exp: 612 / 762.2Syn Z: 0.09

Background carrier burden — how many people carry a rare variant somewhere in ADGRA2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 29

1,854 rare PASS variants

Rare truncating (LoF)

1 in 330

201 rare PASS variants

Rare synonymous (reference)

1 in 56

939 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ADGRA2. 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 31	1 in 530
South Asian	~43k	1 in 24	1 in 300
Remaining (unassigned)	~30k	1 in 24	1 in 330
European (Finnish)	~27k	1 in 77	1 in 680
Admixed American	~22k	1 in 29	1 in 230
African / African American	~21k	1 in 27	1 in 1,700
East Asian	~20k	1 in 29	1 in 740
Ashkenazi Jewish	~13k	1 in 64	1 in 290
Middle Eastern	~2,884	1 in 27	1 in 510

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 17 of 19 coding exons well covered in gnomAD exomes; exons 1, 18 marginal. Genomes: all 19.? see exons ↓