SLC30A10

solute carrier family 30 member 10, the group of Solute carrier family 30

Basic information

Region (hg38): 1:219685427-219959018

Links

ENSG00000196660 ∙ NCBI:55532 ∙ OMIM:611146 ∙ HGNC:25355 ∙ Uniprot:Q6XR72 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cirrhosis - dystonia - polycythemia - hypermanganesemia syndrome (Supportive), mode of inheritance: AR
• cirrhosis - dystonia - polycythemia - hypermanganesemia syndrome (Strong), mode of inheritance: AR
• cirrhosis - dystonia - polycythemia - hypermanganesemia syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypermanganesemia with dystonia 1	AR	Hematologic	The condition can involve hypermagnesemia, with gastrointestinal, neurologic, and other sequelae, and chelation therapy has been described as beneficial in some individuals	Biochemical; Gastrointestinal; Hematologic; Neurologic	11040156; 18087599; 18392750; 21596707; 22341971; 22341972

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC30A10 gene.

• not provided (1 variants)
• Hypermanganesemia with dystonia, polycythemia, and cirrhosis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC30A10 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	53	1	56
missense			92	5		97
nonsense			2			2
start loss						0
frameshift	1					1
inframe indel			1			1
splice donor/acceptor (+/-2bp)			1			1
splice region			2	2		4
non coding			16	24	32	72
Total	1	0	114	82	33

Variants in SLC30A10

This is a list of pathogenic ClinVar variants found in the SLC30A10 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-219914261-A-G		Hypermanganesemia with dystonia, polycythemia, and cirrhosis	Likely benign (Jan 13, 2018)
1-219914320-TG-T		Hypermanganesemia with dystonia, polycythemia, and cirrhosis	Benign (Jun 14, 2016)
1-219914361-C-G		Hypermanganesemia with dystonia, polycythemia, and cirrhosis	Uncertain significance (Jan 13, 2018)
1-219914361-C-T		Hypermanganesemia with dystonia, polycythemia, and cirrhosis	Benign (Jan 12, 2018)
1-219914504-G-A		Hypermanganesemia with dystonia, polycythemia, and cirrhosis	Likely benign (Jan 13, 2018)
1-219914602-C-T		Hypermanganesemia with dystonia, polycythemia, and cirrhosis	Uncertain significance (Apr 27, 2017)
1-219914705-C-A		Hypermanganesemia with dystonia, polycythemia, and cirrhosis	Benign (Jan 12, 2018)
1-219914819-C-T		Hypermanganesemia with dystonia, polycythemia, and cirrhosis	Uncertain significance (Jan 12, 2018)
1-219914983-T-A		Hypermanganesemia with dystonia, polycythemia, and cirrhosis	Uncertain significance (Jan 12, 2018)
1-219914997-A-C		Hypermanganesemia with dystonia, polycythemia, and cirrhosis	Uncertain significance (Jan 13, 2018)
1-219915052-G-A		Hypermanganesemia with dystonia, polycythemia, and cirrhosis	Uncertain significance (Jan 12, 2018)
1-219915093-C-T		Hypermanganesemia with dystonia, polycythemia, and cirrhosis	Uncertain significance (Jan 12, 2018)
1-219915134-C-T		Hypermanganesemia with dystonia, polycythemia, and cirrhosis	Uncertain significance (Mar 23, 2018)
1-219915173-G-A		Hypermanganesemia with dystonia, polycythemia, and cirrhosis	Benign (Sep 04, 2018)
1-219915210-T-C		Hypermanganesemia with dystonia, polycythemia, and cirrhosis	Uncertain significance (Jan 13, 2018)
1-219915277-A-G		Hypermanganesemia with dystonia, polycythemia, and cirrhosis	Uncertain significance (Jan 13, 2018)
1-219915332-C-G		Hypermanganesemia with dystonia, polycythemia, and cirrhosis	Uncertain significance (Jan 13, 2018)
1-219915334-G-C		Hypermanganesemia with dystonia, polycythemia, and cirrhosis	Benign/Likely benign (Jan 24, 2019)
1-219915379-C-T		Hypermanganesemia with dystonia, polycythemia, and cirrhosis	Uncertain significance (Jan 12, 2018)
1-219915458-C-A			Likely benign (Aug 19, 2021)
1-219915458-C-G			Likely benign (Sep 23, 2022)
1-219915458-C-T		Hypermanganesemia with dystonia, polycythemia, and cirrhosis	Conflicting classifications of pathogenicity (Dec 05, 2023)
1-219915459-G-A			Uncertain significance (May 14, 2022)
1-219915470-A-G			Conflicting classifications of pathogenicity (Aug 01, 2024)
1-219915480-T-C			Uncertain significance (Jun 20, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC30A10	protein_coding	protein_coding	ENST00000366926	4	273221

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.980	0.0205	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.58	197	270	0.730	0.0000132	3119
Missense in Polyphen		39	87.104	0.44774		967
Synonymous	0.130	119	121	0.985	0.00000665	1017
Loss of Function	3.20	0	11.9	0.00	5.73e-7	147

LoF frequencies by population

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

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a pivotal role in manganese transport. Manganese is an essential cation for the function of several enzymes, including some crucially important for the metabolism of neurotransmitters and other neuronal metabolic pathways. However, elevated levels of manganese are cytotoxic and induce oxidative stress, mitochondrial dysfunction and apoptosis. Acts as manganese efflux transporter and confers protection against manganese- induced cell death (PubMed:22341972, PubMed:22341971, PubMed:25319704, PubMed:27226609, PubMed:27307044). Also acts as zinc transporter involved in zinc homeostasis. Seems to mediate zinc transport into early endosomes and recycling endosomes to prevent zinc toxicity; the function may be regulated by heterodimerization with other zinc transporters of the SLC30A subfamily. The SLC30A3:SLC30A10 heterodimer is involved in zinc transport-dependent regulation of the EGFR/ERK transduction pathway in endosomes. May be involved in regulation of zinc- dependent senescence of vascular smooth muscle cells (PubMed:22706290, PubMed:22427991, PubMed:26728129). {ECO:0000269|PubMed:22341971, ECO:0000269|PubMed:22341972, ECO:0000269|PubMed:22427991, ECO:0000269|PubMed:25319704, ECO:0000269|PubMed:27226609, ECO:0000305|PubMed:22706290}.
• Disease: DISEASE: Hypermanganesemia with dystonia 1 (HMNDYT1) [MIM:613280]: A metabolic autosomal recessive disorder characterized by dystonia, parkinsonism, extrapyramidal signs, severe hypermanganesemia, polycythemia, and chronic hepatic disease, including steatosis and cirrhosis. {ECO:0000269|PubMed:22341971, ECO:0000269|PubMed:22341972, ECO:0000269|PubMed:25319704}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Zinc homeostasis;Transport of bile salts and organic acids, metal ions and amine compounds;SLC-mediated transmembrane transport;Transport of small molecules;Metal ion SLC transporters (Consensus)

Recessive Scores

• pRec: 0.125

Intolerance Scores

• loftool: 0.0689
• rvis_EVS: -0.4
• rvis_percentile_EVS: 26.53

Haploinsufficiency Scores

• pHI: 0.115
• hipred: Y
• hipred_score: 0.544
• ghis: 0.514

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0230

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc30a10
• 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); 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); endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: slc30a10
• Affected structure: nucleate erythrocyte
• Phenotype tag: abnormal
• Phenotype quality: increased amount

Gene ontology

• Biological process: manganese ion transport;zinc ion transport;epidermal growth factor receptor signaling pathway;negative regulation of neuron apoptotic process;positive regulation of ERK1 and ERK2 cascade;manganese ion transmembrane transport;regulation of zinc ion transport;negative regulation of reactive oxygen species biosynthetic process;cellular response to angiotensin;regulation of cellular response to manganese ion;negative regulation of cellular senescence
• Cellular component: early endosome;Golgi apparatus;plasma membrane;integral component of membrane;recycling endosome
• Molecular function: manganese ion transmembrane transporter activity;protein binding