ADGRE5

Chr 19

adhesion G protein-coupled receptor E5

Also known as: CD97, TM7LN1

This gene encodes a member of the EGF-TM7 subfamily of adhesion G protein-coupled receptors, which mediate cell-cell interactions. These proteins are cleaved by self-catalytic proteolysis into a large extracellular subunit and seven-span transmembrane subunit, which associate at the cell surface as a receptor complex. The encoded protein may play a role in cell adhesion as well as leukocyte recruitment, activation and migration, and contains multiple extracellular EGF-like repeats which mediate binding to chondroitin sulfate and the cell surface complement regulatory protein CD55. Expression of this gene may play a role in the progression of several types of cancer. Alternatively spliced transcript variants encoding multiple isoforms with 3 to 5 EGF-like repeats have been observed for this gene. This gene is found in a cluster with other EGF-TM7 genes on the short arm of chromosome 19. [provided by RefSeq, Jun 2011]

0
Active trials
12
Pubs (1 yr)
14
P/LP submissions
0%
P/LP missense
0.60
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryADGRE5
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
14 unique Pathogenic / Likely Pathogenic· 154 VUS of 213 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.60LOEUF
pLI 0.000
Z-score 3.63
OE 0.40 (0.270.60)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.80Z-score
OE missense 0.90 (0.830.97)
451 obs / 501.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.40 (0.270.60)
00.351.4
Missense OE0.90 (0.830.97)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 17 / 42.6Missense obs/exp: 451 / 501.7Syn Z: -0.47
DN
0.73top 25%
GOF
0.75top 25%
LOF
0.2092th %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

213 submitted variants in ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic1
VUS154
Likely Benign19
Benign3
13
Pathogenic
1
Likely Pathogenic
154
VUS
19
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
13
0
13
Likely Pathogenic
0
0
1
0
1
VUS
0
150
4
0
154
Likely Benign
0
17
0
2
19
Benign
0
0
1
2
3
Total0167194190

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

View in ClinVar →

Protein Context — Lollipop Plot

ADGRE5 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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