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CNNM2

cyclin and CBS domain divalent metal cation transport mediator 2, the group of Cyclin and CBS domain divalent metal cation transport mediators

Basic information

Region (hg38): 10:102918293-103090222

Previous symbols: [ "ACDP2" ]

Links

ENSG00000148842NCBI:54805OMIM:607803HGNC:103Uniprot:Q9H8M5AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • hypomagnesemia, seizures, and intellectual disability 1 (Strong), mode of inheritance: AD
  • familial primary hypomagnesemia with normocalciuria and normocalcemia (Supportive), mode of inheritance: AD
  • hypomagnesemia, seizures, and intellectual disability 1 (Strong), mode of inheritance: AR
  • renal hypomagnesemia 6 (Strong), mode of inheritance: AD
  • hypomagnesemia, seizures, and intellectual disability 1 (Definitive), mode of inheritance: Semidominant

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Hypomagnesemia 6, renalARRenalCorrection of electrolyte abnormalities may help treatment, though complete correction was not achieved in some described individualsNeurologic; Renal12584272; 21397062; 24699222
In Hypomagnesemia, seizures, and impaired intellectual development 1, magnesium supplementation has not been described as effective

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CNNM2 gene.

  • not provided (194 variants)
  • Renal hypomagnesemia 6 (64 variants)
  • Hereditary spastic paraplegia 45 (27 variants)
  • Inborn genetic diseases (20 variants)
  • Hypomagnesemia, seizures, and intellectual disability 1 (17 variants)
  • Hypomagnesemia, seizures, and intellectual disability 1;Renal hypomagnesemia 6 (13 variants)
  • Hereditary spastic paraplegia (5 variants)
  • Renal hypomagnesemia 6;Hypomagnesemia, seizures, and intellectual disability 1 (5 variants)
  • not specified (3 variants)
  • CNNM2-related condition (2 variants)
  • Renal Hypomagnesemia, Dominant (1 variants)
  • See cases (1 variants)
  • CNNM2-related neurodevelopmental disorder and hypomagnesemia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CNNM2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
8
clinvar
60
clinvar
10
clinvar
78
missense
5
clinvar
3
clinvar
85
clinvar
7
clinvar
1
clinvar
101
nonsense
1
clinvar
1
clinvar
1
clinvar
3
start loss
0
frameshift
3
clinvar
3
clinvar
6
inframe indel
4
clinvar
4
splice donor/acceptor (+/-2bp)
0
splice region
2
2
1
5
non coding
1
clinvar
33
clinvar
27
clinvar
29
clinvar
90
Total 7 7 134 94 40

Highest pathogenic variant AF is 0.00000657

Variants in CNNM2

This is a list of pathogenic ClinVar variants found in the CNNM2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
10-102918371-A-T Renal hypomagnesemia 6 Benign (Jan 13, 2018)298632
10-102918416-G-A Renal hypomagnesemia 6 Uncertain significance (Jan 13, 2018)298633
10-102918492-T-A Uncertain significance (Sep 13, 2023)2864063
10-102918495-C-T Likely benign (Jan 22, 2024)2096566
10-102918508-A-G Uncertain significance (Feb 01, 2022)1675434
10-102918527-G-A Renal hypomagnesemia 6;Hypomagnesemia, seizures, and intellectual disability 1 Uncertain significance (Nov 27, 2023)1430577
10-102918529-C-G Renal hypomagnesemia 6 Uncertain significance (Jan 13, 2018)298634
10-102918568-C-T Uncertain significance (Apr 15, 2023)2178214
10-102918570-C-T Renal hypomagnesemia 6 Benign (Dec 28, 2023)757526
10-102918575-G-T Likely benign (Oct 11, 2023)2909399
10-102918580-A-T Uncertain significance (Aug 03, 2022)1912813
10-102918592-C-T CNNM2-related condition Uncertain significance (Apr 12, 2023)2633481
10-102918592-CG-C Renal hypomagnesemia 6 Pathogenic (Mar 11, 2011)30683
10-102918593-G-A Renal hypomagnesemia 6 Benign (Jan 31, 2024)298635
10-102918595-G-A Inborn genetic diseases Uncertain significance (Apr 25, 2022)1918583
10-102918598-A-G Renal hypomagnesemia 6;Hypomagnesemia, seizures, and intellectual disability 1 Uncertain significance (Oct 24, 2022)1375331
10-102918600-C-T Likely benign (Jun 05, 2022)1536780
10-102918605-AGGCGGCTGCGG-A Likely pathogenic (Jul 06, 2018)817123
10-102918613-G-T Inborn genetic diseases Uncertain significance (Dec 13, 2022)2333986
10-102918614-C-A Uncertain significance (Oct 23, 2023)2906884
10-102918618-G-A Likely benign (Aug 17, 2023)2076811
10-102918623-T-C Hypomagnesemia, seizures, and intellectual disability 1 Pathogenic (Jan 22, 2021)996041
10-102918644-G-A Uncertain significance (Oct 10, 2022)1952254
10-102918675-G-A CNNM2-related condition Likely benign (Feb 26, 2020)3052157
10-102918686-A-G Uncertain significance (Sep 01, 2019)871141

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
CNNM2protein_codingprotein_codingENST00000369878 8171929
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.9950.00479125740071257470.0000278
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense4.412194950.4420.00002745646
Missense in Polyphen15103.290.145231266
Synonymous-1.192392171.100.00001281823
Loss of Function4.48329.00.1030.00000147340

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.00009070.0000905
Ashkenazi Jewish0.000.00
East Asian0.00005560.0000544
Finnish0.000.00
European (Non-Finnish)0.00003610.0000352
Middle Eastern0.00005560.0000544
South Asian0.000.00
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Divalent metal cation transporter. Mediates transport of divalent metal cations in an order of Mg(2+) > Co(2+) > Mn(2+) > Sr(2+) > Ba(2+) > Cu(2+) > Fe(2+) (By similarity). {ECO:0000250|UniProtKB:Q3TWN3}.;
Disease
DISEASE: Hypomagnesemia, seizures, and mental retardation (HOMGSMR) [MIM:616418]: A disease characterized by renal wasting of magnesium, low serum magnesium, seizures, and variable degrees of delayed psychomotor development. {ECO:0000269|PubMed:24699222}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.121

Intolerance Scores

loftool
0.0785
rvis_EVS
-0.98
rvis_percentile_EVS
8.75

Haploinsufficiency Scores

pHI
0.333
hipred
Y
hipred_score
0.673
ghis
0.580

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.946

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Cnnm2
Phenotype
mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span);

Zebrafish Information Network

Gene name
cnnm2b
Affected structure
optic tectum
Phenotype tag
abnormal
Phenotype quality
increased size

Gene ontology

Biological process
magnesium ion homeostasis;magnesium ion transmembrane transport
Cellular component
integral component of membrane;basolateral plasma membrane;intracellular membrane-bounded organelle
Molecular function
ATP binding;magnesium ion transmembrane transporter activity