SLC30A7

protein-coding

solute carrier family 30 member 7, the group of Solute carrier family 30

Gene summary

Zinc functions as a cofactor for numerous enzymes, nuclear factors, and hormones and as an intra- and intercellular signal ion. Members of the zinc transporter (ZNT)/SLC30 subfamily of the cation diffusion facilitator family, such as SLC30A7, permit cellular efflux of zinc (Seve et al., 2004 [PubMed 15154973]).[supplied by OMIM, Mar 2008]

MANE transcript

NM_133496.5

Inheritance

AD, AR

ClinVar variants

P:4U:57B:9

Top phenotype

Ziegler-Huang syndrome

gnomAD constraint

pLI —, LoF o/e 0.64

Max pathogenic AF

—

Genomic locus

chr1:100,896,076-100,996,260

External References & Databases

Ensembl (ENSG00000162695)

Transcript & Mutation Effects

hg38 • Region Span ~100.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Joubert syndromeLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0018772

Submitter: G2P

Joubert syndromeMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0018772

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Ziegler-Huang syndromeAR

Manifestation: Allergy/Immunology/Infectious; Endocrine; Hematologic

Intervention: Allergy/Immunology/Infectious; Endocrine; Hematologic

Rationale: The condition can include hormone deficiencies, and awareness may allow medical management; Due to mineral abnormalities, supplementation has been described as necessary; The condition may involve bone marrow failure, including neutropenia and thrombocytopenia, and the need for interventions such as RBC transfusions has been described

Refs: 36821639

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLC30A7 variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 51

not providedTotal: 28

Ziegler-Huang syndromeTotal: 4

Decreased testicular sizeTotal: 1

Severe early-onset pulmonary alveolar proteinosis due to MARS deficiencyTotal: 1

Testicular atrophyTotal: 1

Joubert syndrome 1Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_133496.5. 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			1 clinvar	5 clinvar	1 clinvar	7
missense	1 clinvar		56 clinvar	2 clinvar	1 clinvar	60
nonsense						0
start loss						0
frameshift		2 clinvar				2
splice donor/acceptor (+/-2bp)		1 clinvar				1
Total	1	3	57	7	2	70

Highest pathogenic variant AF is 0.000011628797

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_133496.5	RefSeq	NP_598003.2	11	MANE Select
ENST00000357650.9	Ensembl	ENSP00000350278.4	11	MANE Select
NM_001144884.2	RefSeq	NP_001138356.1	11	Standard
ENST00000370111.4	Ensembl	ENSP00000359129.4	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Zinc homeostasis
Peptide hormone metabolism
Metabolism of proteins
Transport of bile salts and organic acids, metal ions and amine compounds
SLC-mediated transmembrane transport

Biological Process

zinc ion transport
sequestering of zinc ion
cation transmembrane transport

Molecular Function

cation transmembrane transporter activity

Cellular Component

cytoplasm
Golgi apparatus
integral component of membrane
cytoplasmic vesicle
vesicle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000370112
Coding exons: 11
Length: 85678
Individuals with no LoFs: 125712
Homozygous LoFs: 0
Heterozygous LoFs: 36
Defined: 125748
p: 0.000143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.467	182	201	0.907	0.00000921	2485
Missense (PolyPhen)		72	83.253	0.86483		1068
Synonymous	-0.435	79	74.2	1.06	0.00000393	718
Loss of Function	1.49	13	20.2	0.643	8.56e-7	248

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00021	0.00020	rare
South Asian	0.00010	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Seems to facilitate zinc transport from the cytoplasm into the Golgi apparatus. Partly regulates cellular zinc homeostasis. Required with ZNT5 for the activation of zinc- requiring enzymes, alkaline phosphatases (ALPs). Transports zinc into the lumens of the Golgi apparatus and the vesicular compartments where ALPs locate, thus, converting apoALPs to holoALPs. Required with ZNT5 and ZNT6 for the activation of TNAP (By similarity). {ECO:0000250, ECO:0000269|PubMed:15276077, ECO:0000269|PubMed:15994300}.;

Recessive Scores

pRec: 0.122

Intolerance Scores

LoFtool: 0.740
RVIS EVS: -0.69
RVIS percentile EVS: 14.97

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.786

Gene Damage Prediction

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