SLC39A5

solute carrier family 39 member 5, the group of Solute carrier family 39

Basic information

Region (hg38): 12:56230048-56237846

Links

ENSG00000139540 ∙ NCBI:283375 ∙ OMIM:608730 ∙ HGNC:20502 ∙ Uniprot:Q6ZMH5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• myopia 24, autosomal dominant (Strong), mode of inheritance: AD
• myopia 24, autosomal dominant (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myopia 24	AD	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	Ophthalmologic	24891338

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC39A5 gene.

• Inborn genetic diseases (30 variants)
• not provided (16 variants)
• Myopia 24, autosomal dominant (4 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC39A5 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				3		3
missense			29	6	6	41
nonsense	1		1			2
start loss						0
frameshift		1	1			2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding					1	1
Total	1	1	31	9	7

Highest pathogenic variant AF is 0.00000657

Variants in SLC39A5

This is a list of pathogenic ClinVar variants found in the SLC39A5 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-56231261-T-C		Myopia 24, autosomal dominant	Benign (Jul 15, 2021)
12-56231284-T-C			Benign (May 20, 2018)
12-56231287-C-T		not specified	Uncertain significance (Dec 27, 2023)
12-56231297-A-G		not specified	Uncertain significance (Mar 07, 2023)
12-56231313-C-G		not specified	Likely benign (May 08, 2023)
12-56231330-T-C			Benign (Jun 01, 2022)
12-56231366-C-A		not specified	Uncertain significance (Jan 11, 2023)
12-56231374-C-A		not specified	Uncertain significance (Jan 29, 2024)
12-56231415-C-G		Myopia 24, autosomal dominant	Pathogenic (Aug 01, 2014)
12-56231417-G-A			Uncertain significance (Feb 14, 2023)
12-56231418-C-T		SLC39A5-related disorder	Likely benign (Jul 01, 2022)
12-56231444-G-A		not specified	Uncertain significance (Jun 09, 2022)
12-56231453-G-A		not specified	Uncertain significance (Sep 01, 2021)
12-56231469-G-A			Likely benign (May 17, 2018)
12-56231498-T-TG		Myopia 24, autosomal dominant	Likely pathogenic (Oct 14, 2020)
12-56231510-G-A		not specified	Uncertain significance (Apr 12, 2022)
12-56231565-C-T		SLC39A5-related disorder	Likely benign (May 28, 2019)
12-56232700-C-G		not specified	Uncertain significance (Jul 11, 2023)
12-56232789-C-T			Benign (Dec 13, 2018)
12-56232790-G-A		not specified	Likely benign (Mar 30, 2022)
12-56232792-G-A		not specified	Uncertain significance (Aug 30, 2021)
12-56232805-C-T		not specified	Uncertain significance (Feb 15, 2023)
12-56232819-C-T		not specified	Likely benign (Sep 17, 2021)
12-56234859-C-G			Likely benign (Sep 10, 2018)
12-56234869-G-A			Benign (Jun 29, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC39A5	protein_coding	protein_coding	ENST00000266980	10	7798

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.38e-11	0.251	125440	1	306	125747	0.00122

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.238	310	322	0.963	0.0000190	3342
Missense in Polyphen		136	128.92	1.0549		1428
Synonymous	0.403	148	154	0.959	0.00000911	1315
Loss of Function	0.833	18	22.2	0.809	0.00000130	213

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00195	0.00195
Ashkenazi Jewish	0.00124	0.00109
East Asian	0.000761	0.000761
Finnish	0.000705	0.000647
European (Non-Finnish)	0.00155	0.00149
Middle Eastern	0.000761	0.000761
South Asian	0.00105	0.000948
Other	0.00189	0.00179

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May play a role in polarized cells by carrying out serosal-to-mucosal zinc transport. Plays a role in eye development. Could regulate the BMP/TGF-beta (bone morphogenetic protein/transforming growth factor-beta) signaling pathway and modulates extracellular matrix (ECM) proteins of the sclera (PubMed:24891338). Seems to play a central role in controlling organismal zinc status (By similarity). {ECO:0000250|UniProtKB:Q9D856, ECO:0000269|PubMed:24891338}.
• Disease: DISEASE: Myopia 24, autosomal dominant (MYP24) [MIM:615946]: A refractive error of the eye, in which parallel rays from a distant object come to focus in front of the retina, vision being better for near objects than for far. {ECO:0000269|PubMed:24891338, ECO:0000269|PubMed:25525168}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Nuclear Receptors Meta-Pathway;NRF2 pathway;Zinc homeostasis;Zinc influx into cells by the SLC39 gene family;Transport of bile salts and organic acids, metal ions and amine compounds;SLC-mediated transmembrane transport;Transport of small molecules;Metal ion SLC transporters;Zinc transporters (Consensus)

Intolerance Scores

• loftool: 0.909
• rvis_EVS: -0.37
• rvis_percentile_EVS: 28.2

Haploinsufficiency Scores

• pHI: 0.131
• hipred: N
• hipred_score: 0.170
• ghis: 0.416

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.146

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc39a5
• Phenotype: homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; digestive/alimentary phenotype; skeleton phenotype; immune system phenotype; liver/biliary system phenotype

Gene ontology

• Biological process: eye development;cellular zinc ion homeostasis;BMP signaling pathway;cellular response to zinc ion starvation;positive regulation of mRNA splicing, via spliceosome;neural precursor cell proliferation;G1 to G0 transition involved in cell differentiation;zinc ion import across plasma membrane
• Cellular component: integral component of plasma membrane;basolateral plasma membrane;extracellular exosome
• Molecular function: molecular_function;zinc ion transmembrane transporter activity