CNNM3

Chr 2

cyclin and CBS domain divalent metal cation transport mediator 3

Also known as: ACDP3, SLC70A3

NCBI Gene: 26505 ENSG00000168763 UniProt: Q8NE01 OMIM: 607804

The CNNM3 protein is a transmembrane metal transporter involved in magnesium ion homeostasis. Mutations cause autosomal recessive hypomagnesemia with seizures and intellectual disability, typically presenting in infancy or early childhood. The gene shows low constraint against loss-of-function variants, consistent with its recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable transmembrane transporter activity. Predicted to be involved in magnesium ion homeostasis. Located in membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.97

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.97LOEUF

pLI 0.000

Z-score 1.66

OE 0.62 (0.41–0.97)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.76Z-score

OE missense 0.88 (0.79–0.97)

256 obs / 292.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.62 (0.41–0.97)

0≤0.351.4

Missense OE?0.88 (0.79–0.97)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 14 / 22.5Missense obs/exp: 256 / 292.4Syn Z: -0.47

Background carrier burden — how many people carry a rare variant somewhere in CNNM3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 57

1,040 rare PASS variants

Rare truncating (LoF)

1 in 1,400

148 rare PASS variants

Rare synonymous (reference)

1 in 100

545 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CNNM3. 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 59	1 in 1,700
South Asian	~43k	1 in 58	1 in 930
Remaining (unassigned)	~30k	1 in 46	1 in 2,100
European (Finnish)	~27k	1 in 91	1 in 490
Admixed American	~22k	1 in 60	1 in 910
African / African American	~21k	1 in 54	1 in 930
East Asian	~20k	1 in 44	1 in 2,200
Ashkenazi Jewish	~13k	1 in 160	≈ 1 in 3,000
Middle Eastern	~2,884	1 in 51	≈ 1 in 2,000

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): 7 of 8 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 8.? see exons ↓