SLC39A8

solute carrier family 39 member 8, the group of Solute carrier family 39

Basic information

Region (hg38): 4:102251079-102431258

Links

ENSG00000138821 ∙ NCBI:64116 ∙ OMIM:608732 ∙ HGNC:20862 ∙ Uniprot:Q9C0K1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• SLC39A8-CDG (Strong), mode of inheritance: AR
• SLC39A8-CDG (Supportive), mode of inheritance: AR
• Leigh syndrome (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital disorder of glycosylation, type IIn	AR	Allergy/Immunology/Infectious	Individuals have been described with recurrent infections, and awareness may allow prompt management and prophylactic measures	Allergy/Immunology/Infectious; Biochemical; Musculoskeletal; Neurologic	26637978; 26637979
Dietary galactose has been described as having biochemical but unclear clinical benefit

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC39A8 gene.

• not provided (125 variants)
• SLC39A8-CDG (19 variants)
• Inborn genetic diseases (17 variants)
• not specified (1 variants)
• Inflammatory bowel disease 1 (1 variants)
• - (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC39A8 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				17	3	20
missense	1	4	41	4	2	52
nonsense		3	3			6
start loss						0
frameshift	1		10			11
inframe indel			1			1
splice donor/acceptor (+/-2bp)			5			5
splice region			4	2	1	7
non coding			1	18	28	47
Total	2	7	61	39	33

Highest pathogenic variant AF is 0.0000263

Variants in SLC39A8

This is a list of pathogenic ClinVar variants found in the SLC39A8 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-102253152-C-T			Benign (Jul 27, 2018)
4-102253159-C-CG			Benign (Jul 27, 2018)
4-102253164-C-T			Benign (Jul 27, 2018)
4-102253268-T-C			Benign (Sep 05, 2018)
4-102253334-A-G			Benign (Jul 27, 2018)
4-102253496-T-G			Likely benign (Oct 16, 2018)
4-102253571-T-C			Benign (Sep 05, 2018)
4-102253662-G-A			Benign (Jul 27, 2018)
4-102259518-C-G		SLC39A8-related disorder	Likely benign (Mar 03, 2020)
4-102259718-C-T			Benign (Jul 27, 2018)
4-102261982-G-A		SLC39A8-CDG	Uncertain significance (Jul 29, 2023)
4-102262778-T-C			Benign (Jul 27, 2018)
4-102262907-C-T			Benign (May 22, 2021)
4-102262932-A-G			Benign (Jul 27, 2018)
4-102263047-C-T			Likely benign (Jun 23, 2022)
4-102263055-C-G		SLC39A8-CDG	Uncertain significance (Dec 06, 2021)
4-102263056-G-A			Likely benign (Sep 10, 2018)
4-102263068-A-G			Likely benign (Feb 14, 2023)
4-102263082-G-A			Benign (Jan 25, 2024)
4-102263090-G-T			Uncertain significance (May 14, 2022)
4-102263140-A-G			Likely benign (Jun 29, 2022)
4-102263144-G-A		SLC39A8-CDG	Pathogenic (May 04, 2022)
4-102263168-C-G			Uncertain significance (Feb 03, 2022)
4-102263174-A-G			Uncertain significance (Aug 17, 2022)
4-102263204-G-C			Likely benign (Sep 22, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC39A8	protein_coding	protein_coding	ENST00000394833	8	180218

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.669	0.331	125709	0	4	125713	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.10	187	234	0.798	0.0000112	2982
Missense in Polyphen		52	94.066	0.55281		1210
Synonymous	1.20	79	93.7	0.843	0.00000487	938
Loss of Function	3.10	3	16.7	0.180	7.70e-7	223

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000290	0.0000290
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000177	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as a manganese and zinc influx transporter (PubMed:12504855, PubMed:26637978). Plays a role in manganese reabsorption in the proximal tubule of the kidney and in manganese uptake into the brain (PubMed:26637978). {ECO:0000269|PubMed:12504855, ECO:0000305|PubMed:26637978}.
• Disease: DISEASE: Congenital disorder of glycosylation 2N (CDG2N) [MIM:616721]: A form of congenital disorder of glycosylation, a genetically heterogeneous group of autosomal recessive, multisystem disorders caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. {ECO:0000269|PubMed:26637978, ECO:0000269|PubMed:26637979}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Ferroptosis - Homo sapiens (human);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)

Recessive Scores

• pRec: 0.128

Intolerance Scores

• loftool: 0.356
• rvis_EVS: 0.17
• rvis_percentile_EVS: 65.76

Haploinsufficiency Scores

• pHI: 0.153
• hipred: Y
• hipred_score: 0.765
• ghis: 0.472

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.589

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc39a8
• 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); skeleton phenotype

Gene ontology

• Biological process: zinc ion transport;cellular zinc ion homeostasis;cadmium ion transmembrane transport;zinc ion import across plasma membrane
• Cellular component: plasma membrane;integral component of plasma membrane;organelle membrane
• Molecular function: zinc ion transmembrane transporter activity