JAM3

Chr 11AR

junctional adhesion molecule 3

Also known as: JAM-2, JAM-3, JAM-C, JAMC

JAM3 encodes a junctional adhesion protein that localizes to tight junctions and mediates cell-to-cell interactions by serving as a receptor for JAM2, playing roles in hematopoietic stem cell retention, leukocyte migration, and angiogenesis. Mutations cause autosomal recessive hemorrhagic destruction of the brain, subependymal calcification, and congenital cataracts. The gene shows tolerance to loss-of-function variation (pLI 0.0006), consistent with the recessive inheritance pattern observed clinically.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

Hemorrhagic destruction of the brain, subependymal calcification, and cataractsMIM #613730
AR
1
Active trials
26
Pubs (1 yr)
112
P/LP submissions
6%
P/LP missense
0.84
LOEUF
LOF
Mechanism· G2P
Clinical SummaryJAM3
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
105 unique Pathogenic / Likely Pathogenic· 109 VUS of 340 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.84LOEUF
pLI 0.001
Z-score 2.04
OE 0.47 (0.270.84)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.87Z-score
OE missense 1.19 (1.061.33)
205 obs / 172.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.47 (0.270.84)
00.351.4
Missense OE1.19 (1.061.33)
00.61.4
Synonymous OE1.24
01.21.6
LoF obs/exp: 8 / 17.1Missense obs/exp: 205 / 172.9Syn Z: -1.54
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongJAM3-related hemorrhagic destruction of the brain, subependymal calcification, and cataractsLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7035th %ile
GOF
0.6735th %ile
LOF
0.3066th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

340 submitted variants in ClinVar

Classification Summary

Pathogenic93
Likely Pathogenic12
VUS109
Likely Benign85
Benign36
Conflicting2
93
Pathogenic
12
Likely Pathogenic
109
VUS
85
Likely Benign
36
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
4
83
0
93
Likely Pathogenic
0
2
10
0
12
VUS
1
85
22
1
109
Likely Benign
0
4
49
32
85
Benign
0
1
33
2
36
Conflicting
2
Total79619735337

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

View in ClinVar →

Protein Context — Lollipop Plot

JAM3 · protein map & ClinVar variants

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

Clinical Literature
Open Research Assistant →