CNNM2

Summary

CNNM2 (cyclin and CBS domain divalent metal cation transport mediator 2, HGNC:103) is a protein-coding gene on chromosome 10q24.32, encoding Metal transporter CNNM2 (Q9H8M5). Divalent metal cation transporter.

This gene encodes a member of the ancient conserved domain containing protein family. Members of this protein family contain a cyclin box motif and have structural similarity to the cyclins. The encoded protein may play an important role in magnesium homeostasis by mediating the epithelial transport and renal reabsorption of Mg2+. Mutations in this gene are associated with renal hypomagnesemia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 54805 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypomagnesemia, seizures, and intellectual disability 1 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 61 (top 1% of genes corpus-wide)
• Clinical variants (ClinVar): 2,920 total — 23 pathogenic, 38 likely-pathogenic (top 1% of genes corpus-wide)
• Regional missense constraint (gnomAD): 3 of 9 regions constrained (≈27% of expected missense variation)
• GTEx eGene: eQTL in 16 tissues, sQTL in 4 (q < 0.05)
• Phenotypes (HPO): 19
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.31 (highly constrained)
• MANE Select transcript: NM_017649

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:103
Approved symbol	CNNM2
Name	cyclin and CBS domain divalent metal cation transport mediator 2
Location	10q24.32
Locus type	gene with protein product
Status	Approved
Aliases	SLC70A2
Ensembl gene	ENSG00000148842
Ensembl biotype	protein_coding
OMIM	607803
Entrez	54805

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 7 protein_coding, 5 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000369878

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 1, TSL 3: 1

ENST00000369878, ENST00000369875, ENST00000433628, ENST00000475511, ENST00000970832, ENST00000993758, ENST00000993759, ENST00000993760, ENST00001010184, ENST00001110031, ENST00001119355, ENST00001119356, ENST00001140995

RefSeq mRNA: 3 — MANE Select: NM_017649 NM_017649, NM_199076, NM_199077

CCDS: CCDS44474, CCDS44475, CCDS7543

Canonical transcript exons

ENST00000369878 — 8 exons

Exon	Start	End
ENSE00000987732	103068629	103068722
ENSE00001025936	103071774	103071839
ENSE00001288096	103076971	103090222
ENSE00001661582	103054329	103054466
ENSE00001788039	102918294	102920101
ENSE00001806333	103056795	103056964
ENSE00002517953	103049707	103049850
ENSE00003490174	103076086	103076270

Expression profiles

Bgee: expression breadth ubiquitous, 234 present calls, max score 96.63.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.1725 / max 212.0592, expressed in 1631 samples.

Highest expression (Bgee): secondary oocyte, oocyte, adrenal gland, sural nerve, adrenal gland cortex.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CNNM2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 16 tissues and its splicing (sQTL) in 4 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

20 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	eqtl	1.5e-12	+0.30	10:103169618:CA:C
Brain Frontal Cortex BA9	eqtl	2.1e-09	+0.39	10:103154183:T:C
Artery Tibial	eqtl	1.4e-04	-0.22	10:103182487:T:G
Skin Sun Exposed Lower leg	eqtl	5.4e-04	-0.12	10:103079395:T:C
Brain Cerebellum	eqtl	7.3e-04	+0.27	10:102727625:C:T
Adrenal Gland	eqtl	2.8e-03	-0.15	10:102457835:T:C
Testis	eqtl	6.6e-03	+0.18	10:102509460:G:A
Brain Caudate basal ganglia	eqtl	1.0e-02	+0.16	10:102875346:G:A
Cells Cultured fibroblasts	eqtl	1.1e-02	-0.08	10:103455175:T:C
Brain Cerebellar Hemisphere	eqtl	1.8e-02	+0.30	10:103154183:T:C
Brain Hippocampus	sqtl	2.3e-02	+0.74	10:101985076:T:TAC
Thyroid	eqtl	3.0e-02	+0.37	10:103591257:G:C
Adipose Visceral Omentum	eqtl	3.2e-02	+0.20	10:102415138:G:A
Skin Not Sun Exposed Suprapubic	eqtl	3.5e-02	-0.09	10:103107106:C:T
Brain Hippocampus	eqtl	3.7e-02	+0.24	10:103154183:T:C
Esophagus Muscularis	sqtl	3.7e-02	-1.43	10:102434323:C:T
Heart Left Ventricle	sqtl	3.8e-02	+0.72	10:103029737:G:A
Cells Cultured fibroblasts	sqtl	4.2e-02	+1.14	10:103206162:C:T
Adipose Subcutaneous	eqtl	4.7e-02	+0.34	10:102221926:C:T
Cells EBV-transformed lymphocytes	eqtl	4.8e-02	-0.36	10:103634573:CGAGTATAAGGT:C

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
106778	4.9816	1588
106779	1.1737	472
106782	0.0173	6

Top tissues by expression

showing 100 of 282 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	96.63	gold quality
oocyte	CL:0000023	93.03	gold quality
right adrenal gland	UBERON:0001233	82.35	gold quality
sural nerve	UBERON:0015488	82.24	gold quality
right adrenal gland cortex	UBERON:0035827	82.17	gold quality
choroid plexus epithelium	UBERON:0003911	82.13	gold quality
left adrenal gland	UBERON:0001234	81.98	gold quality
left adrenal gland cortex	UBERON:0035825	81.51	gold quality
popliteal artery	UBERON:0002250	81.15	gold quality
tibial artery	UBERON:0007610	81.11	gold quality
middle temporal gyrus	UBERON:0002771	80.99	silver quality
adrenal gland	UBERON:0002369	80.66	gold quality
adrenal cortex	UBERON:0001235	80.29	gold quality
endothelial cell	CL:0000115	80.26	silver quality
mucosa of transverse colon	UBERON:0004991	80.03	gold quality
pancreatic ductal cell	CL:0002079	79.88	silver quality
islet of Langerhans	UBERON:0000006	79.39	gold quality
Brodmann (1909) area 23	UBERON:0013554	79.19	gold quality
adrenal tissue	UBERON:0018303	78.97	gold quality
aorta	UBERON:0000947	78.82	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.43	silver quality
primary visual cortex	UBERON:0002436	78.02	gold quality
left coronary artery	UBERON:0001626	77.87	gold quality
medial globus pallidus	UBERON:0002477	77.82	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.36	gold quality
cortical plate	UBERON:0005343	77.29	gold quality
ventricular zone	UBERON:0003053	77.17	gold quality
coronary artery	UBERON:0001621	77.07	gold quality
stromal cell of endometrium	CL:0002255	76.95	gold quality
prefrontal cortex	UBERON:0000451	76.74	gold quality
rectum	UBERON:0001052	76.62	gold quality
nephron tubule	UBERON:0001231	76.54	gold quality
ganglionic eminence	UBERON:0004023	76.47	gold quality
ascending aorta	UBERON:0001496	76.02	gold quality
thoracic aorta	UBERON:0001515	75.94	gold quality
right coronary artery	UBERON:0001625	75.78	gold quality
transverse colon	UBERON:0001157	75.64	gold quality
cranial nerve II	UBERON:0000941	74.80	gold quality
descending thoracic aorta	UBERON:0002345	74.53	gold quality
globus pallidus	UBERON:0001875	74.21	gold quality
Brodmann (1909) area 46	UBERON:0006483	73.74	gold quality
Brodmann (1909) area 9	UBERON:0013540	73.67	gold quality
cortex of kidney	UBERON:0001225	73.48	gold quality
right frontal lobe	UBERON:0002810	73.43	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	73.26	gold quality
gall bladder	UBERON:0002110	73.21	gold quality
hypothalamus	UBERON:0001898	73.20	gold quality
adult mammalian kidney	UBERON:0000082	73.18	gold quality
occipital lobe	UBERON:0002021	73.18	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	73.12	gold quality
metanephric glomerulus	UBERON:0004736	73.07	gold quality
frontal cortex	UBERON:0001870	73.05	gold quality
neocortex	UBERON:0001950	73.03	gold quality
monocyte	CL:0000576	72.89	gold quality
renal glomerulus	UBERON:0000074	72.88	gold quality
right lobe of liver	UBERON:0001114	72.83	gold quality
tendon	UBERON:0000043	72.79	gold quality
kidney epithelium	UBERON:0004819	72.74	gold quality
mononuclear cell	CL:0000842	72.68	gold quality
right uterine tube	UBERON:0001302	72.64	gold quality
adenohypophysis	UBERON:0002196	72.60	gold quality
tibialis anterior	UBERON:0001385	72.56	silver quality
leukocyte	CL:0000738	72.54	gold quality
left ovary	UBERON:0002119	72.45	gold quality
right ovary	UBERON:0002118	72.41	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	72.30	gold quality
pancreas	UBERON:0001264	72.27	gold quality
kidney	UBERON:0002113	72.26	gold quality
pituitary gland	UBERON:0000007	72.24	gold quality
colon	UBERON:0001155	72.10	gold quality
skin of leg	UBERON:0001511	72.09	gold quality
placenta	UBERON:0001987	71.89	gold quality
spinal cord	UBERON:0002240	71.80	gold quality
large intestine	UBERON:0000059	71.78	gold quality
right hemisphere of cerebellum	UBERON:0014890	71.76	gold quality
cerebral cortex	UBERON:0000956	71.75	gold quality
cerebellar cortex	UBERON:0002129	71.70	gold quality
colonic mucosa	UBERON:0000317	71.63	gold quality
cerebellar hemisphere	UBERON:0002245	71.60	gold quality
cingulate cortex	UBERON:0003027	71.58	gold quality
skin of abdomen	UBERON:0001416	71.45	gold quality
calcaneal tendon	UBERON:0003701	71.42	gold quality
metanephros	UBERON:0000081	71.35	gold quality
anterior cingulate cortex	UBERON:0009835	71.32	gold quality
body of uterus	UBERON:0009853	71.31	gold quality
colonic epithelium	UBERON:0000397	71.18	silver quality
forebrain	UBERON:0001890	71.18	gold quality
right lung	UBERON:0002167	71.17	gold quality
tendon of biceps brachii	UBERON:0008188	71.12	silver quality
nucleus accumbens	UBERON:0001882	71.07	gold quality
telencephalon	UBERON:0001893	71.04	gold quality
putamen	UBERON:0001874	71.02	gold quality
intestine	UBERON:0000160	71.01	gold quality
central nervous system	UBERON:0001017	71.01	gold quality
brain	UBERON:0000955	70.98	gold quality
cerebellum	UBERON:0002037	70.93	gold quality
caudate nucleus	UBERON:0001873	70.82	gold quality
substantia nigra	UBERON:0002038	70.82	gold quality
granulocyte	CL:0000094	70.73	gold quality
left lobe of thyroid gland	UBERON:0001120	70.73	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	2492.31
E-GEOD-131882	yes	2451.07
E-ANND-3	no	6.24

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Choroid plexus	tissue	102.1
Nucleus accumbens	tissue	32.0
Parathyroid gland	tissue	29.6
Postcentral gyrus	tissue	28.0
Locus coeruleus	tissue	27.2
Superior colliculi	tissue	27.1
Cerebellum	tissue	26.8
Olfactory bulb	tissue	26.1
Basal ganglia	tissue	25.4
Hippocampus	tissue	25.4
Thalamus	tissue	25.1
Putamen	tissue	24.2
Ventral forebrain	tissue	23.5
Pons	tissue	23.2
Cerebral cortex	tissue	22.8
Somatosensory cortex	tissue	22.8
Septum	tissue	22.3
Hippocampal formation	tissue	21.9
Occipital cortex	tissue	21.3
Hypothalamus	tissue	21.2
Motor cortex	tissue	20.9
Midbrain	tissue	20.7
Substantia nigra	tissue	20.6
Prefrontal cortex	tissue	20.5
Medulla oblongata	tissue	19.7
Retrosplenial and cingulate cortex	tissue	19.0
Insular cortex	tissue	18.8
Retrosplenial cortex	tissue	18.6
Temporal cortex	tissue	18.6
Entorhinal cortex	tissue	18.5
Periaqueductal gray	tissue	17.0
Amygdala	tissue	16.8
Caudate putamen	tissue	13.6
Spinal cord	tissue	13.1
Frontal cortex	tissue	8.8
Bone marrow	tissue	8.8
Kidney	tissue	8.5
Placenta	tissue	8.2
Corpus callosum	tissue	8.1
Adrenal gland	tissue	7.9
Colon	tissue	6.6
Rectum	tissue	6.0
Ovary	tissue	5.6
Pituitary gland	tissue	5.3
Thyroid gland	tissue	5.2
Retina	tissue	4.6
Fallopian tube	tissue	4.5
Small intestine	tissue	4.2
Liver	tissue	3.9
Gallbladder	tissue	3.8
Testis	tissue	3.7
Duodenum	tissue	3.6
Smooth muscle	tissue	3.4
Endometrium 1	tissue	3.3
Pancreas	tissue	3.1
Cervix	tissue	2.8
Vagina	tissue	2.8
Seminal vesicle	tissue	2.8
Stomach 1	tissue	2.7
Lung	tissue	2.7

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Parieto-temporal junction (white matter) (40.3), Flocculonodular lobe (37.4), Vermis (36.8), Cerebellar cortex (36.2), Temporal white matter (36.2).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CNNM2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 88 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-4779	99.86	66.50	1583

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.312, missense Z 5.02 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000369878 splits into 9 regions with different missense tolerance; 3 are missense-constrained (≈27% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
10:102,918,481–102,918,631	98 / 73.6	1.33	no
10:102,918,632–102,918,756	37 / 58.5	0.63	no
10:102,918,757–102,918,869	15 / 58.1	0.26	yes (p 1.5e-08)
10:102,918,870–102,919,180	100 / 151.9	0.66	no
10:102,919,181–102,919,593	49 / 183.7	0.27	yes (p 2.8e-23)
10:102,919,594–102,919,688	27 / 40.7	0.66	no
10:102,919,689–102,919,840	14 / 68.6	0.20	yes (p 4.3e-11)
10:102,919,841–103,068,651	171 / 304.8	0.56	no
10:103,068,652–103,077,177	194 / 227.6	0.85	no

Literature-anchored findings (GeneRIF, showing 18)

• ACDP2 splice-variant 1 is a functional Mg2+-transporting entity per se. (PMID:20519162)
• The CNNM2 locus is associated with serum Mg(2+) concentrations. (PMID:21397062)
• analysis of structure of CNNM2 and its post-translational modifications (PMID:22399287)
• crystals of CNNM2 belonged to space groups P2(1)2(1)2 and I222 (or I2(1)2(1)2(1)) and diffracted X-rays to 2.0 and 3.6 A resolution, respectively, using synchrotron radiation (PMID:23027747)
• Our findings suggest that the genetic variant in the CNNM2 gene could be implicated in the pathogenesis of schizophrenia through the gray matter volumetric vulnerability of the orbital regions in the inferior frontal gyri. (PMID:24160291)
• This CNNM2 risk variant rs7914558 may have an impact on neural systems relevant to social cognition. (PMID:24311551)
• Cells expressing mutated CNNM2 proteins did not show increased Mg(2+) uptake. (PMID:24699222)
• meta-analysis of two Caucasian cohorts did not show an association between five aneurysm associated loci and sporadic brain Arteriovenous malformations. (PMID:25053769)
• The T568I mutation causes the magnesium transporter, CNNM2, to become ’locked’ in its flat form. (PMID:25184538)
• this study implicates altered neural expression of BORCS7, AS3MT, and NT5C2 in susceptibility to schizophrenia arising from genetic variation at the chromosome 10q24 locus (PMID:27004590)
• Sensitivity of CNNM2 expression to extracellular Mg(2+) depletion depends on cell type. (PMID:27068403)
• In this large-scale, Han Chinese population-based genetic association study for genetic susceptibility to schizophrenia of a three-gene cluster region, AS3MT-CNNM2-NT5C2, two SNPs with independent effects, rs11191419 and rs11191514, were identified. Rs11191419 is located on the 5’ (potential promoter) region of AS3MT, while rs11191514 is located in one of the introns of CNNM2. (PMID:27401531)
• CNNM2 single nucleotide polymorphisms association with the risk of hypertension in Chinese Han population. (PMID:30180964)
• This study determined the first crystal structures of the cyclic nucleotide-binding homology (CNBH) domain domains of CNNM2 and CNNM3 at 2.6 and 1.9 A resolutions. (PMID:30341174)
• Novel variant in the CNNM2 gene associated with dominant hypomagnesemia. (PMID:32997713)
• The phenotypic and genetic spectrum of patients with heterozygous mutations in cyclin M2 (CNNM2). (PMID:33600043)
• Decreased CNNM2 expression in prefrontal cortex affects sensorimotor gating function, cognition, dendritic spine morphogenesis and risk of schizophrenia. (PMID:37715107)
• Hypomagnesaemia with varying degrees of extrarenal symptoms as a consequence of heterozygous CNNM2 variants. (PMID:38519529)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	cnnm2a	ENSDARG00000061195
danio_rerio	cnnm2b	ENSDARG00000078733
mus_musculus	Cnnm2	ENSMUSG00000064105
rattus_norvegicus	Cnnm2	ENSRNOG00000020113
drosophila_melanogaster	uex	FBGN0262124
caenorhabditis_elegans		WBGENE00011260
caenorhabditis_elegans		WBGENE00016343
caenorhabditis_elegans		WBGENE00016879

Paralogs (3): CNNM1 (ENSG00000119946), CNNM4 (ENSG00000158158), CNNM3 (ENSG00000168763)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2151054) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 22 distinct phenotype terms.

Mouse phenotype (MP)	Records
embryonic growth retardation	2
increased bone mineral density	1
abnormal vascular development	1
microcephaly	1
abnormal liver development	1
abnormal brain development	1
exencephaly	1
microphthalmia	1
abnormal homeostasis	1
edema	1
hemorrhage	1
abnormal cardiovascular development	1
spina bifida	1
decreased systemic arterial diastolic blood pressure	1
decreased systemic arterial systolic blood pressure	1
decreased circulating magnesium level	1
lethality throughout fetal growth and development, complete penetrance	1
preweaning lethality, complete penetrance	1
embryonic lethality during organogenesis, incomplete penetrance	1
lethality during fetal growth through weaning, complete penetrance	1
abnormal head shape	1
abnormal head size	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Rickettsia rickettsii str. ‘Sheila Smith’	A8GTI4	99.7%	Diamond
Rickettsia conorii str. Malish 7	Q92GI2	99.7%	Diamond
Rickettsia bellii OSU 85-389	A8GUH1	99.3%	Diamond
Rickettsia bellii RML369-C	Q1RGX2	99.3%	Diamond
Rickettsia massiliae MTU5	A8F2M1	99.0%	Diamond
Rickettsia felis Marseille-URRWFXCal2	Q4UK99	99.0%	Diamond
Rickettsia akari str. Hartford	A8GPR9	95.6%	Diamond
Rickettsia typhi str. Wilmington	Q68W10	93.7%	Diamond
Arabidopsis thaliana	Q8VZI2	87.1%	Diamond
Buchnera aphidicola str. Sg (Schizaphis graminum)	Q8K9C0	84.8%	Diamond
Haemophilus influenzae Rd KW20	Q57368	81.3%	Diamond
Pasteurella multocida subsp. multocida str. Pm70	Q9CM13	81.3%	Diamond
Xenopus tropicalis	A0JPA0	66.1%	Diamond
Schizosaccharomyces pombe 972h-	Q9USJ3	56.7%	Diamond
Saccharomyces cerevisiae S288C	Q12296	56.6%	Diamond
Brachyspira hyodysenteriae	Q54318	39.1%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
BORCS7-ASMT	ncRNA	100528007
NT5C2	protein-coding	22978
AS3MT	protein-coding	57412
BORCS7	protein-coding	119032
RPEL1	protein-coding	729020

Protein

Protein identifiers

Metal transporter CNNM2 — Q9H8M5 (reviewed: Q9H8M5)

Alternative names: Ancient conserved domain-containing protein 2, Cyclin-M2

All UniProt accessions (1): Q9H8M5

UniProt curated annotations — full annotation on UniProt →

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+).

Subcellular location. Cell membrane.

Tissue specificity. Widely expressed. Expressed at higher level in brain, kidney and placenta, while it is weakly expressed in skeletal muscle. In the kidney, it is expressed in the distal convoluted tubule and the thick ascending limb of Henle loop.

Disease relevance. Hypomagnesemia 6 (HOMG6) [MIM:613882] A renal disease characterized by severely lowered serum magnesium levels in the absence of other electrolyte disturbances. Affected individuals show an inappropriately normal urinary magnesium excretion, demonstrating a defect in tubular reabsorption. Age of clinical onset is highly variable and some affected individuals are asymptomatic. The disease is caused by variants affecting the gene represented in this entry. Hypomagnesemia, seizures, and impaired intellectual development 1 (HOMGSMR1) [MIM:616418] A disease characterized by renal wasting of magnesium, low serum magnesium, seizures, and variable degrees of delayed psychomotor development. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Shares weak sequence similarity with the cyclin family, hence its name. However, it has no cyclin-like function in vivo.

Similarity. Belongs to the ACDP family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9H8M5-1	1	yes
Q9H8M5-2	2
Q9H8M5-3	3

RefSeq proteins (3): NP_060119, NP_951058, NP_951059 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000644	CBS_dom	Domain
IPR002550	CNNM	Domain
IPR014710	PpnP-like_jellyroll	Homologous_superfamily
IPR044751	Ion_transp-like_CBS	Domain
IPR045095	ACDP	Family
IPR046342	CBS_dom_sf	Homologous_superfamily
IPR057492	Ig_CNNM1/2/4_N	Domain

Pfam: PF00571, PF01595, PF25511, PF25562

Enzyme classification (BRENDA)

• EC 7.2.2.14 — P-type Mg2+ transporter (BRENDA: 30 organisms, 43 substrates, 51 inhibitors, 23 Km, 2 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
MG2+	0.006–0.05	8
NI2+	0.002–0.4	5
ATP	1.5–2.8	2
CO2+	0.04–0.08	2
MG2+[SIDE 1]	0.01–0.015	2

UniProt features (68 total): helix 16, strand 16, turn 7, sequence variant 6, topological domain 5, domain 3, splice variant 3, transmembrane region 3, sequence conflict 3, region of interest 2, chain 1, modified residue 1, glycosylation site 1, intramembrane region 1

Structure

Experimental structures (PDB)

7 structures by resolution:

PDB	Title	Method	Resolution (Å)
4IYS	Structural and ligand binding properties of the Bateman domain of human magnesium …	X-RAY DIFFRACTION	1.8
4IY0	Structural and ligand binding properties of the Bateman domain of human magnesium …	X-RAY DIFFRACTION	1.9
6DJ3	Crystal structure of CNNM2 cyclic nucleotide-binding homology domain	X-RAY DIFFRACTION	2.6
4IY4	Structural and ligand binding properties of the Bateman domain of human magnesium …	X-RAY DIFFRACTION	2.9
8F6D	Crystal structure of the CNNM2 CBS-pair domain in complex with ARL15	X-RAY DIFFRACTION	3.2
6N7E	Crystal structure of the cytosolic domain of human CNNM2 in complex with AMP-PNP and Mg2+	X-RAY DIFFRACTION	3.5
4IY2	Structural and ligand binding properties of the Bateman domain of human magnesium …	X-RAY DIFFRACTION	3.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H8M5-F1	71.70	0.29

Human Protein Atlas

Protein class: Transporters, Transporter channels and pores, Predicted membrane proteins, Disease related genes, Potential drug targets, Human disease related genes, Congenital disorders of metabolism, Other congenital disorders of metabolism

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): vesicles

Antibody reliability (HPA): IF approved

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1)

Type	Positions
Phosphoserine	761

Glycosylation sites (1)

Type	Positions
N-linked (glcnac…) asparagine	112

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 174 (showing top): BENPORATH_ES_WITH_H3K27ME3, NKX25_02, AP4_Q6, GOBP_MAGNESIUM_ION_TRANSPORT, CAGCTG_AP4_Q5, GOBP_MONOATOMIC_CATION_TRANSPORT, MCAATNNNNNGCG_UNKNOWN, MYOD_01, GOBP_MONOATOMIC_ION_HOMEOSTASIS, SABATES_COLORECTAL_ADENOMA_DN, E12_Q6, MILI_PSEUDOPODIA_CHEMOTAXIS_DN, GOBP_TRANSMEMBRANE_TRANSPORT, PARENT_MTOR_SIGNALING_UP, GOBP_HOMEOSTATIC_PROCESS

GO Biological Process (3): magnesium ion homeostasis (GO:0010960), monoatomic ion transport (GO:0006811), magnesium ion transmembrane transport (GO:1903830)

GO Molecular Function (2): ATP binding (GO:0005524), magnesium ion transmembrane transporter activity (GO:0015095)

GO Cellular Component (4): plasma membrane (GO:0005886), basolateral plasma membrane (GO:0016323), glutamatergic synapse (GO:0098978), synapse (GO:0045202)

GO top-level categories

16 GO namespaces:

Category	Terms
monoatomic cation homeostasis	1
inorganic ion homeostasis	1
transport	1
magnesium ion transport	1
monoatomic cation transmembrane transport	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
metal ion transmembrane transporter activity	1
magnesium ion transmembrane transport	1
membrane	1
cell periphery	1
basal plasma membrane	1
plasma membrane region	1
synapse	1
cell junction	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 2 of 9 annotations. The rest are phylogenetic / computational / electronic (IEA).

2 experimentally-supported GO terms:

GO term	NS	Evidence
magnesium ion homeostasis	BP	mutant phenotype
basolateral plasma membrane	CC	mutant phenotype

Protein interactions and networks

STRING

showing 15 of 824 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CNNM2	STARD13	Q9Y3M8	772
CNNM2	SLC41A1	Q8IVJ1	755
CNNM2	TRPM6	Q9BX84	751
CNNM2	NT5C2	P49902	716
CNNM2	SLC41A2	Q96JW4	655
CNNM2	AS3MT	Q9HBK9	655
CNNM2	SLC41A3	Q96GZ6	654
CNNM2	CLDN16	Q9Y5I7	643
CNNM2	FBN2	P35556	639
CNNM2	LIMK1	P53667	638
CNNM2	RBBP8	Q99708	629
CNNM2	TRPM7	Q96QT4	606
CNNM2	MRS2	Q9HD23	594
CNNM2	BORCS7	Q96B45	591
CNNM2	NIPAL1	Q6NVV3	576

IntAct

BioGRID (61 interactions; top human partners by supporting records): PTP4A2 (Affinity Capture-MS; 6 records), PTP4A1 (Affinity Capture-MS; 3 records), ARL15 (Affinity Capture-MS; 2 records), BTNL8 (Affinity Capture-MS; 2 records), ANKH (Affinity Capture-MS), ASIC4 (Affinity Capture-MS), BMPR1A (Proximity Label-MS), BSG (Proximity Label-MS), CANX (Affinity Capture-MS), CAV1 (Proximity Label-MS), CCNF (Affinity Capture-MS), CDC123 (Affinity Capture-MS), CFAP43 (Cross-Linking-MS (XL-MS)), CLEC2D (Affinity Capture-MS), CNNM1 (Co-fractionation)

Disease & clinical

Genetic variants

Variant evidence for CNNM2: 2,920 ClinVar records (61 pathogenic / likely pathogenic); 61 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

2,920 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	23
Likely pathogenic	38
Uncertain significance	383
Likely benign	1776
Benign	613

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 61 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
192324	NM_017649.5(CNNM2):c.1069G>A (p.Glu357Lys)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
3652451	NM_017649.5(CNNM2):c.274del (p.Ala92fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
1098410	NM_017649.5(CNNM2):c.1804C>T (p.Arg602Ter)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
2581787	NM_017649.5(CNNM2):c.980A>G (p.Asn327Ser)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
30683	NM_017649.5(CNNM2):c.117del (p.Ile40fs)	Pathogenic	criteria provided, single submitter	2
1685993	NM_001351169.2(NT5C2):c.1624del (p.Gln542fs)	Pathogenic	criteria provided, single submitter	1
2024104	NM_017649.5(CNNM2):c.1601del (p.Met534fs)	Pathogenic	criteria provided, single submitter	1
2578368	NM_017649.5(CNNM2):c.274G>C (p.Ala92Pro)	Pathogenic	criteria provided, single submitter	1
2578372	NM_017649.5(CNNM2):c.970G>C (p.Val324Leu)	Pathogenic	criteria provided, single submitter	1
2578374	NM_017649.5(CNNM2):c.1291G>A (p.Glu431Lys)	Pathogenic	criteria provided, single submitter	1
2578375	NM_017649.5(CNNM2):c.1310G>A (p.Gly437Glu)	Pathogenic	criteria provided, single submitter	1
2578376	NM_017649.5(CNNM2):c.2384C>A (p.Ser795Ter)	Pathogenic	criteria provided, single submitter	1
2864063	NM_017649.5(CNNM2):c.12T>A (p.Cys4Ter)	Pathogenic	criteria provided, single submitter	1
3339041	NM_017649.5(CNNM2):c.1936del (p.Glu646fs)	Pathogenic	criteria provided, single submitter	1
4731665	NM_017649.5(CNNM2):c.318C>A (p.Tyr106Ter)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore CNNM2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 31 predictions of 1,562):

Position(s)	Effect	Δscore	Sites
10:102921007	acceptor_gain	1.0000
10:103049704	acceptor_gain	1.0000
10:103049705–103049706	acceptor_loss	1.0000	3
10:103056965–103056966	donor_loss	1.0000	5
10:103068627–103068628	acceptor_loss	1.0000	6
10:103068723–103068724	donor_loss	1.0000	5
10:103076084–103076085	acceptor_loss	1.0000	3
10:103076271–103076272	donor_loss	1.0000	5
10:103076950	acceptor_gain	1.0000
10:103076963	acceptor_gain	1.0000

AlphaMissense

3,153 missense substitutions predicted likely pathogenic (of 5,706 scored), across 631 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M383	9	0.971	0.998
M280	9	0.968	1.000
M417	9	0.963	0.999
M88	9	0.879	0.989
M458	9	0.850	0.989
D571	8	1.000	1.000
D583	8	1.000	1.000
H544	8	0.999	1.000
D586	8	0.999	1.000
D156	8	0.998	1.000
F272	8	0.998	1.000
N327	8	0.998	1.000
D558	8	0.998	1.000
N323	8	0.997	1.000
D499	8	0.997	0.999
F120	8	0.996	1.000
D398	8	0.996	0.999
F538	8	0.996	1.000
S273	8	0.995	1.000
D283	8	0.995	0.999

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	6.68e-09
Glioblastoma Multiforme (validation)	favorable	0.000262
Skin Cutaneous Melanoma (TCGA)	favorable	0.000796

Disease associations

OMIM: gene MIM:607803 | disease phenotypes: MIM:602014, MIM:613882, MIM:616418, MIM:613162

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
hypomagnesemia, seizures, and intellectual disability 1	Definitive	Semidominant	5
renal hypomagnesemia 6	Strong	Autosomal dominant

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
hypomagnesemia, seizures, and intellectual disability 1	Definitive	SD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (11 panels, 11 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

11 panels:

Panel	Rating
DDG2P	green
Early onset or syndromic epilepsy	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Likely inborn error of metabolism	green
Paediatric disorders	green
Renal tubulopathies	green
Undiagnosed metabolic disorders	green
Unexplained death in infancy and sudden unexplained death in childhood	green
Unexplained young onset end-stage renal disease	green

Mondo (4): familial primary hypomagnesemia (MONDO:0018100), renal hypomagnesemia 6 (MONDO:0013480), hypomagnesemia, seizures, and intellectual disability 1 (MONDO:0020787), hereditary spastic paraplegia 45 (MONDO:0013165)

Orphanet (4): OBSOLETE: Familial primary hypomagnesemia with normocalciuria and normocalcemia (Orphanet:34527), Autosomal recessive spastic paraplegia type 45 (Orphanet:320396), Moyamoya angiopathy (Orphanet:477768), OBSOLETE: Genetic primary hypomagnesemia (Orphanet:34526)

HPO phenotypes

19 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001324	Muscle weakness
HP:0001344	Absent speech
HP:0002315	Headache
HP:0002321	Vertigo
HP:0002917	Hypomagnesemia
HP:0003593	Infantile onset
HP:0003621	Juvenile onset
HP:0011463	Childhood onset
HP:0025501	Class III obesity
HP:0025708	Early young adult onset
HP:0033759	Impaired renal tubular reabsorption of magnesium
HP:0100954	Open operculum

GWAS associations

showing 30 of 61 associations:

Study	Trait	p-value
GCST90002406_337	Reticulocyte fraction of red cells	6e-156
GCST90002405_538	Reticulocyte count	3e-147
GCST90002386_437	High light scatter reticulocyte percentage of red cells	4e-138
GCST90002385_547	High light scatter reticulocyte count	6e-135
GCST007267_323	Systolic blood pressure	3e-57
GCST004622_17	Reticulocyte count	1e-51
GCST90002392_255	Mean corpuscular volume	4e-27
GCST000395_3	Systolic blood pressure	7e-24
GCST004630_72	Mean corpuscular hemoglobin	2e-21
GCST004946_51	Schizophrenia	4e-20
GCST002539_77	Schizophrenia	6e-19
GCST006803_98	Schizophrenia	7e-18
GCST009685_31	Hypertension	1e-17
GCST001072_2	Blood pressure	4e-17
GCST004602_242	Mean corpuscular volume	5e-17
GCST004521_217	Autism spectrum disorder or schizophrenia	1e-16
GCST007930_132	Medication use (agents acting on the renin-angiotensin system)	2e-16
GCST011703_48	Smoking initiation	6e-16
GCST010867_49	Coronary artery disease	7e-15
GCST007703_63	Systolic blood pressure	8e-15
GCST009600_72	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	3e-14
GCST004521_123	Autism spectrum disorder or schizophrenia	4e-14
GCST007603_17	Smoking initiation	2e-13
GCST002149_2	Schizophrenia	4e-13
GCST010703_273	Brain morphology (MOSTest)	5e-13
GCST007705_31	Pulse pressure	1e-12
GCST007707_55	Hypertension	1e-12
GCST005194_84	Coronary artery disease	2e-12
GCST001074_8	Blood pressure	7e-12
GCST006231_9	Mean arterial pressure	2e-11

EFO canonical traits (from GWAS)

16 canonical traits:

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure
EFO:0004880	urinary arsenic measurement
EFO:0007746	white matter lesion progression measurement
EFO:0007986	reticulocyte count
EFO:0004527	mean corpuscular hemoglobin
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004534	creatine kinase measurement
EFO:0006340	mean arterial pressure
EFO:0005670	smoking initiation
EFO:0005763	pulse pressure measurement
EFO:0009863	anxiety measurement
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0007820	cognitive behavioural therapy
EFO:0004346	neuroimaging measurement
EFO:0004528	mean corpuscular hemoglobin concentration

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

1 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs58700372	mercaptopurine	Metabolism/PK	Genotypes CC + CT are associated with decreased metabolism of mercaptopurine in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype TT.	PMID:33124053

CTD chemical–gene interactions

45 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	5
GSK-J4	increases expression	1
FR900359	increases phosphorylation	1
bisphenol A	increases expression	1
titanium dioxide	decreases methylation	1
trichostatin A	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression, increases abundance	1
coumarin	increases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
dorsomorphin	increases expression, affects cotreatment	1
Dasatinib	increases expression	1
Irinotecan	increases expression	1
Arsenic Trioxide	increases expression	1
Air Pollutants	decreases expression	1
Amiodarone	increases expression	1
Arsenic	increases abundance, increases expression	1
Azacitidine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Caffeine	increases phosphorylation	1
Catechin	affects cotreatment, decreases expression	1
Cisplatin	decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Diazinon	increases methylation	1
Doxorubicin	decreases expression	1
Formaldehyde	increases expression	1
Hydrogen Peroxide	affects expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 278 trials:

NCT	Phase	Status	Title
NCT00282620	Phase 4	UNKNOWN	Magnesium to Reduce Implantable Cardioverter Defibrillator (ICD) Shocks and Improve Patient’s Quality of Life.
NCT00603499	Phase 4	COMPLETED	Magnesium and Metabolic Syndrome
NCT00994006	Phase 4	COMPLETED	The Absorption of Magnesium Oxide Compared to Citrate in Healthy Subjects
NCT03088852	Phase 4	RECRUITING	Magnesium Deficiency In Patients Hospitalized in Internal Medicine Wards
NCT07542548	Phase 4	COMPLETED	D-Cycloserine for Serine Palmitoyltransferase Inhibition
NCT07803276	Phase 4	RECRUITING	Comparison Between Palpatory and Ultrasound-guided Methods for Botulinum Toxin Administration in Spastic Paraplegia
NCT05657860	Phase 4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	Phase 4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	Phase 4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	Phase 4	RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT03812380	Phase 3	TERMINATED	Averting Complications of Proton Pump Inhibitor Therapy by Effervescent Calcium Magnesium Citrate
NCT05998863	Phase 3	WITHDRAWN	EffCaMgCit to Prevent Mineral Metabolism and Renal Complications of Chronic PPI Therapy
NCT02270736	Phase 3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT03961906	Phase 2	COMPLETED	Physiotherapy in Hereditary Spastic Paraplegia
NCT04768166	Phase 2	COMPLETED	Testing Miglustat Administration in Subjects With Spastic Paraplegia 11
NCT02304302	Phase 2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	Phase 2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	Phase 2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	Phase 2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT06117020	Phase 1	COMPLETED	Single and Multiple Ascending Dose Study of MTR-601 in Healthy Individuals
NCT05273320	Phase 1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	Phase 1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	Phase 1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	Phase 1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	Phase 1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT02216877	Phase 1/2	COMPLETED	Magnesium Supplementation for Hypomagnesemia in Chronic Kidney Disease
NCT04382157	Phase 1/2	UNKNOWN	Magnesium Replacement and Hyperglycemia After Kidney Transplantation
NCT01700998	Not specified	COMPLETED	Magnesium Replacement Therapy to Prevent Acute Renal Failure in Critically Ill Patients
NCT02690012	Not specified	COMPLETED	Feasibility of Using an Integrated Consent Model to Compare Two Standard of Care Regimens for the Management of Hypomagnesemia From Anti-Cancer Therapies
NCT03976440	Not specified	UNKNOWN	Simplified Regional Citrate Anticoagulation Protocols for CVVH, CVVHDF and SLED: a Pilot Study
NCT04351451	Not specified	COMPLETED	Hypomagnesemia and Hypocalcemia Association Following Thyroidectomy
NCT04426994	Not specified	COMPLETED	Hypomagnesemia Associated With Proton-Pump Inhibitor Use
NCT06353750	Not specified	UNKNOWN	Intracellular Magnesium and Heart Failure
NCT06855550	Not specified	COMPLETED	Postoperative Incidence of Atrial Fibrillation Following Cardiac Surgery
NCT07056283	Not specified	RECRUITING	The Study of Urinary Biomarkers in Patients With Hypomagnesemia
NCT07089004	Not specified	COMPLETED	Hypomagnesemia and Its Clinical Outcome
NCT07380542	Not specified	COMPLETED	Dynamic Magnesium Replacement Strategies and 28-Day Mortality in Non-Cardiac Critically Ill Patients With Hypomagnesemia: A Target Trial Emulation
NCT07576621	Not specified	COMPLETED	Association Between Hypomagnesemia and Coagulopathy in Sepsis
NCT02604186	Phase 2/3	COMPLETED	Effects of Botulinum Toxin Injections in Patients With Hereditary Spastic Paraplegia
NCT05518188	Phase 1/2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (Serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
NCT06948019	Phase 1/2	NOT_YET_RECRUITING	Safety and Efficacy of AAV9/AP4B1 (BFB-101) For Patients With AP4B1-related Hereditary Spastic Paraplegia Type 47 (SPG47)
NCT06478238	Early Phase 1	RECRUITING	Calcium Folinate Treatment of Spastic Paraplegia 56
NCT00023075	Not specified	COMPLETED	Nuclear Magnetic Spectroscopy Imaging to Evaluate Primary Lateral Sclerosis, Hereditary Spastic Paraplegia and Amyotrophic Lateral Sclerosis
NCT00136630	Not specified	COMPLETED	Natural History, Genetic Bases and Phenotype-genotype Correlations in Autosomal Dominant Spinocerebellar Degenerations
NCT00140829	Not specified	COMPLETED	SPATAX: Clinical and Genetic Analysis of Cerebellar Ataxias and Spastic Paraplegias
NCT00677768	Not specified	COMPLETED	Validation of Biomarkers in Amyotrophic Lateral Sclerosis (ALS)
NCT01568658	Not specified	ACTIVE_NOT_RECRUITING	Genetic and Physical Study of Childhood Nerve and Muscle Disorders
NCT02327845	Not specified	ACTIVE_NOT_RECRUITING	Phenotype, Genotype & Biomarkers in ALS and Related Disorders
NCT02852278	Not specified	COMPLETED	A Patient Centric Motor Neuron Disease Activities of Daily Living Scale
NCT02859428	Not specified	TERMINATED	Disease Natural History and Biomarkers of SPG3A, SPG4A, and SPG31
NCT03104088	Not specified	COMPLETED	Studying Cognition in SPG4
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NCT04180098	Not specified	COMPLETED	Improving Gait Adaptability in Hereditary Spastic Paraplegia
NCT04256681	Not specified	COMPLETED	SNAP: Measurement of the Subjective Perception of the Symptom in Hereditary Spastic Paraparesis (HSP)
NCT04712812	Not specified	RECRUITING	Registry and Natural History Study for Early Onset Hereditary Spastic Paraplegia
NCT04875416	Not specified	ACTIVE_NOT_RECRUITING	Phenotype, Genotype and Biomarkers 2
NCT04912609	Not specified	COMPLETED	Trehalose Administration in Subjects With Spastic Paraplegia 11 (3AL-SPG11)