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): 10:102918294-103090222

Previous symbols: [ "ACDP2" ]

Links

ENSG00000148842 ∙ NCBI:54805 ∙ OMIM:607803 ∙ HGNC:103 ∙ Uniprot:Q9H8M5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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
• renal hypomagnesemia 6 (Strong), mode of inheritance: AD
• hypomagnesemia, seizures, and intellectual disability 1 (Strong), mode of inheritance: AR
• hypomagnesemia, seizures, and intellectual disability 1 (Definitive), mode of inheritance: Semidominant
• hypomagnesemia, seizures, and intellectual disability 1 (Strong), mode of inheritance: AD
• hypomagnesemia, seizures, and intellectual disability 1 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypomagnesemia 6, renal	AR	Renal	Correction of electrolyte abnormalities may help treatment, though complete correction was not achieved in some described individuals	Neurologic; Renal	12584272; 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 (257 variants)
• Renal_hypomagnesemia_6 (108 variants)
• Hypomagnesemia,_seizures,_and_intellectual_disability_1 (105 variants)
• Inborn_genetic_diseases (53 variants)
• CNNM2-related_disorder (12 variants)
• not_specified (9 variants)
• Intellectual_disability (3 variants)
• CNNM2-Related_Disorders (1 variants)
• CNNM2-related_neurodevelopmental_disorder_and_hypomagnesemia (1 variants)
• See_cases (1 variants)
• Moyamoya_angiopathy (1 variants)
• Neurodevelopmental_abnormality (1 variants)
• 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. These statistics are base on transcript: NM_000017649.5. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			8	95	6	109
missense	11	8	192	10	1	222
nonsense	3	5	2			10
start loss						0
frameshift	4	4	4			12
splice donor/acceptor (+/-2bp)						0
Total	18	17	206	105	7

Highest pathogenic variant AF is 0.0000034778109

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CNNM2	protein_coding	protein_coding	ENST00000369878	8	171929

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.995	0.00479	125740	0	7	125747	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.41	219	495	0.442	0.0000274	5646
Missense in Polyphen		15	103.29	0.14523		1266
Synonymous	-1.19	239	217	1.10	0.0000128	1823
Loss of Function	4.48	3	29.0	0.103	0.00000147	340

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000907	0.0000905
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000556	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000361	0.0000352
Middle Eastern	0.0000556	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

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

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

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