SLC39A5

protein-coding

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

Gene summary

The protein encoded by this gene belongs to the ZIP family of zinc transporters that transport zinc into cells from outside, and play a crucial role in controlling intracellular zinc levels. Zinc is an essential cofactor for many enzymes and proteins involved in gene transcription, growth, development and differentiation. Mutations in this gene have been associated with autosomal dominant high myopia (MYP24). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2014]

MANE transcript

NM_173596.3

Inheritance

ClinVar variants

P:5U:94B:35

Top phenotype

Myopia 24

gnomAD constraint

pLI —, LoF o/e 0.81

Max pathogenic AF

—

Genomic locus

chr12:56,230,049-56,237,846

External References & Databases

Ensembl (ENSG00000139540)

Transcript & Mutation Effects

hg38 • Region Span ~7.8 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

myopia 24, autosomal dominantLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0014411

Submitter: Labcorp Genetics (formerly Invitae)

myopia 24, autosomal dominantSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0014411

Submitter: G2P

myopia 24, autosomal dominantMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0014411

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Myopia 24AD

Manifestation: Ophthalmologic

Intervention: General

Rationale: 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

Refs: 24891338

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLC39A5 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 94

not providedTotal: 23

SLC39A5-related disorderTotal: 18

Myopia 24, autosomal dominantTotal: 12

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_173596.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	10 clinvar	4 clinvar	16
missense	1 clinvar		85 clinvar	16 clinvar	5 clinvar	107
nonsense	1 clinvar	1 clinvar	1 clinvar			3
start loss						0
frameshift		2 clinvar	2 clinvar			4
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	2	3	94	26	9	134

Highest pathogenic variant AF is 0.000018588651

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 103 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_173596.3	RefSeq	NP_775867.2	10	MANE Select
ENST00000454355.7	Ensembl	ENSP00000405360.2	10	MANE Select
NM_001135195.1	RefSeq	NP_001128667.1	10	Standard
ENST00000266980.8	Ensembl	ENSP00000266980.4	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

Biological Process

eye development
cellular zinc ion homeostasis
BMP signaling pathway
cellular response to zinc ion starvation
positive regulation of mRNA splicing, via spliceosome

Molecular Function

molecular_function
zinc ion transmembrane transporter activity

Cellular Component

integral component of plasma membrane
basolateral plasma membrane
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000266980
Coding exons: 10
Length: 7798
Individuals with no LoFs: 125440
Homozygous LoFs: 1
Heterozygous LoFs: 306
Defined: 125747
p: 0.00122

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.238	310	322	0.963	0.0000190	3342
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00043	0.00043	rare
Latino/Admixed American	0.0015	0.0015	notable
Ashkenazi Jewish	0.0012	0.0011	notable
East Asian	0.00076	0.00076	rare
Finnish	0.00071	0.00065	rare
European (Non-Finnish)	0.0015	0.0015	notable
South Asian	0.0011	0.00095	notable
Other	0.0019	0.0018	notable

dbNSFP Gene Annotations

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.;

Intolerance Scores

LoFtool: 0.909
RVIS EVS: -0.37
RVIS percentile EVS: 28.2

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.146

Gene Damage Prediction

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