SLC39A14

solute carrier family 39 member 14, the group of Solute carrier family 39

Basic information

Region (hg38): 8:22367278-22434129

Links

ENSG00000104635 ∙ NCBI:23516 ∙ OMIM:608736 ∙ HGNC:20858 ∙ Uniprot:Q15043 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypermanganesemia with dystonia 2 (Supportive), mode of inheritance: AR
• hyperostosis cranialis interna (Limited), mode of inheritance: AD
• hypermanganesemia with dystonia 2 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hyperostosis cranialis interna; Hypermanganesemia with dystonia 2	AD/AR	Biochemical; Musculoskeletal	In Hyperostosis cranialis interna, surveillance for sequelae related to overgrowth, including hearing evaluation, assessment of signs of increased intracranial pressure and cranial nerve entrapment, can allow early surgical management; In Hypermanganesemia with dystonia 2, individuals have been described with childhood-onset neurodegenerative findings, and medical treatment (with early manganese chelation therapy) has been described as clinically beneficial	Biochemical; Musculoskeletal; Neurologic	20140965; 2300107; 27231142; 29621230

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC39A14 gene.

• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC39A14 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			1	58	9	68
missense		1	59	5	2	67
nonsense	1					1
start loss						0
frameshift			1			1
inframe indel			2		1	3
splice donor/acceptor (+/-2bp)		1	2			3
splice region			1	5		6
non coding		1		20	28	49
Total	1	3	65	83	40

Highest pathogenic variant AF is 0.00000657

Variants in SLC39A14

This is a list of pathogenic ClinVar variants found in the SLC39A14 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-22404458-G-GTTT			Benign (May 24, 2021)
8-22404458-G-GTTTT			Benign (May 25, 2021)
8-22404462-G-T			Benign (May 15, 2021)
8-22404462-GT-G			Benign (May 16, 2021)
8-22404541-A-G			Benign (May 25, 2021)
8-22404585-A-G			Benign (May 15, 2021)
8-22404626-C-T			Benign (May 16, 2021)
8-22404629-G-A		not specified	Benign (Jul 31, 2024)
8-22404670-G-C		not specified	Benign (Jul 31, 2024)
8-22404715-AGCTGCT-A		not specified	Benign (Jul 31, 2024)
8-22404715-A-AGCTGCT			Uncertain significance (Jun 29, 2023)
8-22404731-C-G		not specified	Uncertain significance (Nov 16, 2023)
8-22404733-C-G			Conflicting classifications of pathogenicity (Jan 15, 2024)
8-22404734-G-A			Benign (Aug 01, 2024)
8-22404734-G-T		SLC39A14-related disorder	Conflicting classifications of pathogenicity (Sep 21, 2023)
8-22404736-C-T		Inborn genetic diseases	Uncertain significance (Dec 16, 2021)
8-22404742-A-G			Uncertain significance (Aug 10, 2022)
8-22404761-C-T			Likely benign (Nov 22, 2023)
8-22404762-C-T			Likely benign (Jun 15, 2022)
8-22404768-G-A		Inborn genetic diseases	Conflicting classifications of pathogenicity (Aug 01, 2024)
8-22404768-G-T			Uncertain significance (Aug 03, 2021)
8-22404774-T-C			Uncertain significance (Aug 10, 2022)
8-22404785-C-T			Likely benign (Apr 18, 2023)
8-22404787-C-T			Uncertain significance (Aug 03, 2021)
8-22404789-G-A			Uncertain significance (Sep 05, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC39A14	protein_coding	protein_coding	ENST00000359741	8	66881

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.150	0.849	125737	0	10	125747	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.92	194	285	0.680	0.0000162	3232
Missense in Polyphen		50	112.58	0.44413		1333
Synonymous	0.615	116	125	0.930	0.00000820	999
Loss of Function	2.97	5	19.0	0.264	8.09e-7	220

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000617	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.000548	0.000272
Finnish	0.00	0.00
European (Non-Finnish)	0.0000265	0.0000264
Middle Eastern	0.000548	0.000272
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Broad-scope metal ion transporter with a preference for zinc uptake (PubMed:29621230). Also mediates cellular uptake of nontransferrin-bound iron. {ECO:0000269|PubMed:15642354, ECO:0000269|PubMed:27231142, ECO:0000269|PubMed:29621230}.
• Disease: DISEASE: Hyperostosis cranialis interna (HCIN) [MIM:144755]: An autosomal dominant bone disorder characterized by endosteal hyperostosis and osteosclerosis of the calvaria and the skull base. The progressive bone overgrowth causes entrapment and dysfunction of cranial nerves I, II, V, VII, and VIII, its first symptoms often presenting during the second decade of life. {ECO:0000269|PubMed:29621230}. Note=The disease is caused by mutations affecting the gene represented in this entry. Conditional knockin mice overexpressing Arg-438 variant, which is the mouse equivalent of human variant Leu-441, in osteoblasts have a severe skeletal phenotype marked by a drastic increase in cortical thickness due to an enhanced endosteal bone formation, resembling the underlying pathology in HCI patients. {ECO:0000269|PubMed:29621230}.
• 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: 0.153

Intolerance Scores

• loftool: 0.544
• rvis_EVS: -0.42
• rvis_percentile_EVS: 25.56

Haploinsufficiency Scores

• pHI: 0.146
• hipred: Y
• hipred_score: 0.745
• ghis: 0.496

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.636

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc39a14
• Phenotype: adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; limbs/digits/tail phenotype; skeleton phenotype

Zebrafish Information Network

• Gene name: slc39a14
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: decreased process quality

Gene ontology

• Biological process: cellular zinc ion homeostasis;iron ion transmembrane transport;zinc ion transmembrane transport;zinc ion import across plasma membrane
• Cellular component: cytoplasm;plasma membrane;integral component of plasma membrane;integral component of membrane;lamellipodium
• Molecular function: zinc ion transmembrane transporter activity;ferrous iron transmembrane transporter activity