SLC39A4

solute carrier family 39 member 4, the group of Solute carrier family 39

Basic information

Region (hg38): 8:144409741-144416844

Previous symbols: [ "AEZ" ]

Links

ENSG00000147804 ∙ NCBI:55630 ∙ OMIM:607059 ∙ HGNC:17129 ∙ Uniprot:Q6P5W5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• acrodermatitis enteropathica (Strong), mode of inheritance: AR
• acrodermatitis enteropathica (Strong), mode of inheritance: AR
• acrodermatitis enteropathica (Strong), mode of inheritance: AR
• acrodermatitis enteropathica (Supportive), mode of inheritance: AR
• acrodermatitis enteropathica (Definitive), mode of inheritance: AR
• acrodermatitis enteropathica (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Acrodermatitis enteropathica, zinc-deficiency type	AR	Biochemical	The condition may present with failure to thrive, diarrhea, and dermatitis, and, if untreated, may evolve to include other sequelae of zinc deficiency, including immunodeficiency and neurologic manifestations, and medical management (eg, treatment with oral zinc therapy) can be effective	Biochemical; Dermatologic; Gastrointestinal	4136854; 1090826; 12068297; 19370757; 20883266; 21165302; 21762381; 21906148; 21907902; 22082465; 22166942; 23228939; 23430849
Heterozygous variants have been reported as disease-associated in some reports

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC39A4 gene.

• not provided (624 variants)
• Hereditary acrodermatitis enteropathica (145 variants)
• Inborn genetic diseases (49 variants)
• not specified (6 variants)
• SLC39A4-related condition (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC39A4 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			2	357	8	367
missense	1	4	69	14	6	94
nonsense	11	1	1			13
start loss						0
frameshift	34	4	2			40
inframe indel						0
splice donor/acceptor (+/-2bp)	1	22				23
splice region			3	52	8	63
non coding	1		5	55	13	74
Total	48	31	79	426	27

Highest pathogenic variant AF is 0.000394

Variants in SLC39A4

This is a list of pathogenic ClinVar variants found in the SLC39A4 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-144412477-T-C		Hereditary acrodermatitis enteropathica	Uncertain significance (Jan 13, 2018)
8-144412510-G-A		Hereditary acrodermatitis enteropathica	Uncertain significance (Jan 13, 2018)
8-144412545-G-A		Hereditary acrodermatitis enteropathica	Uncertain significance (Sep 04, 2020)
8-144412547-G-A			Likely benign (May 28, 2023)
8-144412550-G-A			Likely benign (May 11, 2023)
8-144412558-C-T		Hereditary acrodermatitis enteropathica	Uncertain significance (Jan 12, 2018)
8-144412559-G-A			Likely benign (Nov 14, 2021)
8-144412564-G-A			Likely benign (Sep 21, 2023)
8-144412571-C-A			Likely benign (Sep 09, 2020)
8-144412573-G-A			Likely benign (Dec 06, 2023)
8-144412576-G-A			Likely benign (Feb 05, 2023)
8-144412577-C-A			Likely benign (Jan 04, 2024)
8-144412579-G-A		Hereditary acrodermatitis enteropathica	Likely benign (Jan 29, 2024)
8-144412583-G-A			Likely benign (Oct 07, 2022)
8-144412584-G-A			Uncertain significance (Jul 10, 2019)
8-144412586-C-T			Uncertain significance (Mar 07, 2018)
8-144412589-G-A			Likely benign (Jun 06, 2023)
8-144412589-G-C			Likely benign (Jan 14, 2024)
8-144412592-G-A			Likely benign (Apr 15, 2023)
8-144412594-C-G		Hereditary acrodermatitis enteropathica	Likely pathogenic (Jan 30, 2023)
8-144412598-C-A			Likely benign (Jul 17, 2020)
8-144412598-C-G			Likely benign (Dec 09, 2019)
8-144412598-C-T			Likely benign (Sep 16, 2021)
8-144412600-G-A			Likely benign (Feb 08, 2023)
8-144412607-G-A			Likely benign (Oct 22, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC39A4	protein_coding	protein_coding	ENST00000301305	12	7154

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000314	0.997	125662	0	26	125688	0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.295	412	395	1.04	0.0000269	4018
Missense in Polyphen		100	119.41	0.83748		1366
Synonymous	-3.75	273	205	1.33	0.0000169	1417
Loss of Function	2.66	10	24.1	0.415	0.00000105	262

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.000122	0.000109
Finnish	0.0000554	0.0000462
European (Non-Finnish)	0.000223	0.000185
Middle Eastern	0.000122	0.000109
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays an important role in cellular zinc homeostasis as a zinc transporter. Regulated in response to zinc availability (By similarity). {ECO:0000250}.
• Pathway: Mineral absorption - Homo sapiens (human);Nuclear Receptors Meta-Pathway;NRF2 pathway;Zinc homeostasis;Senescence and Autophagy in Cancer;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)

Recessive Scores

• pRec: 0.127

Intolerance Scores

• loftool: 0.530
• rvis_EVS: 1.21
• rvis_percentile_EVS: 93.05

Haploinsufficiency Scores

• pHI: 0.0991
• hipred: N
• hipred_score: 0.172

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.231

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Slc39a4
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; vision/eye phenotype; skeleton phenotype; embryo phenotype; liver/biliary system 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); endocrine/exocrine gland phenotype; muscle phenotype; craniofacial phenotype; cellular phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: cellular zinc ion homeostasis;signal transduction;cellular response to zinc ion starvation;zinc ion import across plasma membrane
• Cellular component: plasma membrane;integral component of plasma membrane;apical plasma membrane;cytoplasmic vesicle;recycling endosome membrane
• Molecular function: zinc ion transmembrane transporter activity