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): 2:96760902-96811874

Previous symbols: [ "ACDP4" ]

Links

ENSG00000158158 ∙ NCBI:26504 ∙ OMIM:607805 ∙ HGNC:105 ∙ Uniprot:Q6P4Q7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Jalili syndrome	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Dental; Ophthalmologic	3236352; 15173235; 19200525; 19200527; 20706282

ClinVar

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

• not provided (21 variants)
• Jalili syndrome (7 variants)
• Retinal dystrophy (1 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			8	126	5	139
missense	1	1	205	2		209
nonsense	9	1				10
start loss						0
frameshift	14	3				17
inframe indel			8	1		9
splice donor/acceptor (+/-2bp)	2	2	1			5
splice region			2	8	1	11
non coding			26	33	14	73
Total	26	7	248	162	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)
2-96760986-A-C		Jalili syndrome	Conflicting classifications of pathogenicity (Jan 13, 2018)
2-96761006-C-G			Uncertain significance (Feb 18, 2022)
2-96761008-G-T			Likely benign (Aug 04, 2023)
2-96761012-G-T			Uncertain significance (Sep 01, 2022)
2-96761017-G-A			Likely benign (Jun 22, 2021)
2-96761018-G-A			Uncertain significance (Jan 15, 2022)
2-96761018-GGCGGGCGCCCGGTCGGCGGACCGGCCC-G			Uncertain significance (Jun 14, 2022)
2-96761033-G-C			Uncertain significance (Jun 14, 2022)
2-96761033-G-T		Inborn genetic diseases	Uncertain significance (Aug 15, 2023)
2-96761036-G-A			Uncertain significance (Mar 19, 2022)
2-96761039-C-G		Inborn genetic diseases	Uncertain significance (Jan 11, 2023)
2-96761042-G-T			Uncertain significance (Sep 15, 2021)
2-96761046-G-A			Uncertain significance (Jan 01, 2024)
2-96761059-C-G			Likely benign (Aug 17, 2023)
2-96761060-C-G		Jalili syndrome	Uncertain significance (Nov 18, 2020)
2-96761060-CTGGCGGCGCCGGTGCTGCTGGTGCTGCTGTGGGCGCTGGGGGCCCGGGGCCAGGGCAGCCCCCAGCAGGGCACGATCGTGGGCA-C		Jalili syndrome	Pathogenic (Feb 01, 2009)
2-96761068-G-A			Likely benign (Nov 13, 2023)
2-96761070-C-T			Uncertain significance (Jul 19, 2022)
2-96761070-CGGTGCTGCT-C			Uncertain significance (Aug 24, 2021)
2-96761077-G-A		Jalili syndrome	Uncertain significance (Jan 13, 2018)
2-96761084-C-T			Likely benign (Oct 05, 2023)
2-96761084-CT-C			Pathogenic (Jul 03, 2022)
2-96761085-T-TGCTGTGGGC			Uncertain significance (Oct 17, 2022)
2-96761090-T-C		Jalili syndrome • Inborn genetic diseases • CNNM4-related disorder	Uncertain significance (Oct 17, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CNNM4	protein_coding	protein_coding	ENST00000377075	7	50990

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.93e-7	0.927	125718	0	30	125748	0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.37	307	448	0.685	0.0000298	5065
Missense in Polyphen		67	133.83	0.50063		1510
Synonymous	-0.363	208	201	1.03	0.0000141	1633
Loss of Function	1.78	14	23.3	0.602	0.00000131	276

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000177	0.000177
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000159	0.000158
Middle Eastern	0.000109	0.000109
South Asian	0.0000327	0.0000327
Other	0.000652	0.000652

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

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

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