MON2

Chr 12

MON2 regulator of endosome-to-Golgi trafficking

NCBI Gene: 23041 ENSG00000061987 UniProt: Q7Z3U7 OMIM: 616822

Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in Golgi to endosome transport; protein targeting to vacuole; and retrograde transport, endosome to Golgi. Located in Golgi apparatus and early endosome membrane. [provided by Alliance of Genome Resources, Jun 2026]

OMIM Research

OMIM ResearchGenerating clinical summary…

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

0.32

LOEUF· LoF intol.

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.32LOEUF

pLI 0.594

Z-score 6.88

OE 0.22 (0.15–0.32)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

3.20Z-score

OE missense 0.69 (0.65–0.74)

607 obs / 873.4 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.22 (0.15–0.32)

0≤0.351.4

Missense OE?0.69 (0.65–0.74)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 20 / 90.8Missense obs/exp: 607 / 873.4Syn Z: 0.33

Background carrier burden — how many people carry a rare variant somewhere in MON2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 44

1,748 rare PASS variants

Rare truncating (LoF)

1 in 1,500

194 rare PASS variants

Rare synonymous (reference)

1 in 80

713 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MON2. 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 60	1 in 1,400
South Asian	~43k	1 in 43	1 in 1,200
Remaining (unassigned)	~30k	1 in 43	1 in 2,500
European (Finnish)	~27k	1 in 120	1 in 1,300
Admixed American	~22k	1 in 47	1 in 3,600
African / African American	~21k	1 in 40	1 in 2,700
East Asian	~20k	1 in 45	≈ 1 in 6,600
Ashkenazi Jewish	~13k	1 in 250	1 in 1,900
Middle Eastern	~2,884	1 in 52	none seen

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): 27 of 35 coding exons well covered in gnomAD exomes; exons 2, 6, 20, 21, 22 and 3 more marginal. Genomes: 34 of 35 (exon 13 below).? see exons ↓