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CNNM4

cyclin and CBS domain divalent metal cation transport mediator 4, the group of Cyclin and CBS domain divalent metal cation transport mediators|MicroRNA protein coding host genes

Basic information

Region (hg38): 2:96760901-96811874

Previous symbols: [ "ACDP4" ]

Links

ENSG00000158158NCBI:26504OMIM:607805HGNC:105Uniprot:Q6P4Q7AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • Jalili syndrome (Supportive), mode of inheritance: AR
  • Jalili syndrome (Strong), mode of inheritance: AR
  • Jalili syndrome (Definitive), mode of inheritance: AR
  • Jalili syndrome (Definitive), mode of inheritance: AR
  • Jalili syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Jalili syndromeARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingDental; Ophthalmologic3236352; 15173235; 19200525; 19200527; 20706282

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CNNM4 gene.

  • not provided (401 variants)
  • Jalili syndrome (96 variants)
  • Inborn genetic diseases (25 variants)
  • not specified (4 variants)
  • Retinitis pigmentosa (2 variants)
  • Retinal dystrophy (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CNNM4 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
10
clinvar
117
clinvar
5
clinvar
132
missense
1
clinvar
1
clinvar
201
clinvar
2
clinvar
205
nonsense
9
clinvar
9
start loss
0
frameshift
13
clinvar
3
clinvar
16
inframe indel
8
clinvar
1
clinvar
9
splice donor/acceptor (+/-2bp)
1
clinvar
2
clinvar
2
clinvar
5
splice region
?
0
non coding
?
26
clinvar
30
clinvar
14
clinvar
70
Total 24 6 247 150 19

Highest pathogenic variant AF is 0.0000131

Variants in CNNM4

This is a list of pathogenic ClinVar variants found in the CNNM4 region.

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

Position Type Phenotype Significance ClinVar
2-96760910-C-T Jalili syndrome Uncertain significance (Jan 13, 2018)337575
2-96760986-A-C Jalili syndrome Conflicting classifications of pathogenicity (Jan 13, 2018)193424
2-96761006-C-G Uncertain significance (Feb 18, 2022)2038789
2-96761008-G-T Likely benign (Mar 19, 2022)1536521
2-96761012-G-T Uncertain significance (Sep 01, 2022)1361444
2-96761017-G-A Likely benign (Jun 22, 2021)1632940
2-96761018-G-A Uncertain significance (Jan 15, 2022)851089
2-96761018-GGCGGGCGCCCGGTCGGCGGACCGGCCC-G Uncertain significance (Jun 14, 2022)1402965
2-96761033-G-C Uncertain significance (Jun 14, 2022)2003546
2-96761033-G-T Inborn genetic diseases Uncertain significance (Aug 15, 2023)2603150
2-96761036-G-A Uncertain significance (Mar 19, 2022)1008521
2-96761039-C-G Inborn genetic diseases Uncertain significance (Jan 11, 2023)2475562
2-96761042-G-T Uncertain significance (Sep 15, 2021)957927
2-96761046-G-A Uncertain significance (Oct 13, 2022)957264
2-96761059-C-G Likely benign (May 25, 2022)1126393
2-96761060-C-G Jalili syndrome Uncertain significance (Sep 01, 2021)337576
2-96761060-CTGGCGGCGCCGGTGCTGCTGGTGCTGCTGTGGGCGCTGGGGGCCCGGGGCCAGGGCAGCCCCCAGCAGGGCACGATCGTGGGCA-C Jalili syndrome Pathogenic (Feb 01, 2009)2853
2-96761068-G-A Likely benign (Dec 01, 2021)2113730
2-96761070-C-T Uncertain significance (Jul 19, 2022)1445304
2-96761070-CGGTGCTGCT-C Uncertain significance (Aug 24, 2021)964838
2-96761077-G-A Jalili syndrome Uncertain significance (Jan 13, 2018)337577
2-96761084-CT-C Pathogenic (Jul 03, 2022)2013699
2-96761085-T-TGCTGTGGGC Uncertain significance (Oct 17, 2022)999867
2-96761090-T-C Jalili syndrome • Inborn genetic diseases Uncertain significance (Oct 17, 2022)288785
2-96761095-G-C Likely benign (Oct 18, 2022)2106564

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
CNNM4protein_codingprotein_codingENST00000377075 750990
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
2.93e-70.9271257180301257480.000119
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense2.373074480.6850.00002985065
Missense in Polyphen67133.830.500631510
Synonymous-0.3632082011.030.00001411633
Loss of Function1.781423.30.6020.00000131276

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0001770.000177
Ashkenazi Jewish0.000.00
East Asian0.0001090.000109
Finnish0.000.00
European (Non-Finnish)0.0001590.000158
Middle Eastern0.0001090.000109
South Asian0.00003270.0000327
Other0.0006520.000652

dbNSFP

Source: dbNSFP

Function
FUNCTION: Probable metal transporter. The interaction with the metal ion chaperone COX11 suggests that it may play a role in sensory neuron functions (By similarity). May play a role in biomineralization and retinal function. {ECO:0000250, ECO:0000269|PubMed:19200525, ECO:0000269|PubMed:19200527}.;

Recessive Scores

pRec
0.109

Intolerance Scores

loftool
0.330
rvis_EVS
-1.15
rvis_percentile_EVS
6.23

Haploinsufficiency Scores

pHI
0.148
hipred
N
hipred_score
0.425
ghis
0.587

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.795

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Cnnm4
Phenotype
digestive/alimentary phenotype; renal/urinary system phenotype; skeleton phenotype; growth/size/body region 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); craniofacial phenotype; homeostasis/metabolism phenotype;

Zebrafish Information Network

Gene name
cnnm4b
Affected structure
retinal ganglion cell
Phenotype tag
abnormal
Phenotype quality
decreased amount

Gene ontology

Biological process
visual perception;magnesium ion homeostasis;sodium ion transmembrane transport;response to stimulus;metal ion homeostasis;enamel mineralization;magnesium ion transmembrane transport
Cellular component
integral component of membrane;basolateral plasma membrane;dendrite;protein-containing complex;neuronal cell body
Molecular function
protein binding;sodium ion transmembrane transporter activity;magnesium ion transmembrane transporter activity