SLC34A3

solute carrier family 34 member 3, the group of Solute carrier family 34

Basic information

Region (hg38): 9:137230757-137236555

Links

ENSG00000198569

∙ NCBI:142680 ∙ OMIM:609826 ∙ HGNC:20305 ∙ Uniprot:Q8N130 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

hereditary hypophosphatemic rickets with hypercalciuria (Supportive), mode of inheritance: AR
hereditary hypophosphatemic rickets with hypercalciuria (Strong), mode of inheritance: AR
hereditary hypophosphatemic rickets with hypercalciuria (Definitive), mode of inheritance: Semidominant

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypophosphatemic rickets with hypercalciuria, hereditary	AR	Renal	The condition can result in sequelae such as severe rickets, and supplementation (eg, with phosphate) can be effective to treat many sequelae	Renal	2983203; 3796683; 1436310; 16358214; 16358215
Heterozygotes may show mild manifestations

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC34A3 gene.

not_provided (562 variants)
Autosomal_recessive_hypophosphatemic_bone_disease (311 variants)
Inborn_genetic_diseases (122 variants)
SLC34A3-related_disorder (69 variants)
not_specified (37 variants)
Kidney_disorder (3 variants)
Hypercalciuria (1 variants)
Hypophosphatemic_nephrolithiasis/osteoporosis_1 (1 variants)
Nephrolithiasis/nephrocalcinosis (1 variants)
Retinitis_pigmentosa_59 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC34A3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001177316.2. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous	1 clinvar		11 clinvar	157 clinvar	4 clinvar	173
missense	4 clinvar	13 clinvar	310 clinvar	25 clinvar	3 clinvar	355
nonsense	5 clinvar	11 clinvar	3 clinvar			19
start loss		2				2
frameshift	17 clinvar	15 clinvar	5 clinvar			37
splice donor/acceptor (+/-2bp)	4 clinvar	22 clinvar	2 clinvar	1 clinvar	1 clinvar	30
Total	31	63	331	183	8

Highest pathogenic variant AF is 0.00072278

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC34A3	protein_coding	protein_coding	ENST00000538474	12	5798

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.89e-14	0.0298	125486	1	212	125699	0.000848

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.29	466	394	1.18	0.0000271	3758
Missense in Polyphen		188	166.58	1.1286		1678
Synonymous	-3.27	251	193	1.30	0.0000148	1367
Loss of Function	0.215	21	22.1	0.951	0.00000105	222

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00123	0.00120
Ashkenazi Jewish	0.00	0.00
East Asian	0.000331	0.000326
Finnish	0.00115	0.00111
European (Non-Finnish)	0.00117	0.00111
Middle Eastern	0.000331	0.000326
South Asian	0.000624	0.000588
Other	0.000833	0.000815

dbNSFP

Source: dbNSFP

Function: FUNCTION: May be involved in actively transporting phosphate into cells via Na(+) cotransport in the renal brush border membrane. Probably mediates 20-30% of the apical influx.;
Disease: DISEASE: Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) [MIM:241530]: Autosomal recessive form of hypophosphatemia characterized by reduced renal phosphate reabsorption and rickets. Increased serum levels of 1,25-dihydroxyvitamin D lead to increase in urinary calcium excretion. {ECO:0000269|PubMed:16358214, ECO:0000269|PubMed:16358215}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Transport of inorganic cations/anions and amino acids/oligopeptides;SLC-mediated transmembrane transport;Transport of small molecules;Type II Na+/Pi cotransporters;Sodium-coupled phosphate cotransporters (Consensus)

Recessive Scores

pRec: 0.173

Intolerance Scores

loftool: 0.239
rvis_EVS: 0.41
rvis_percentile_EVS: 76.54

Haploinsufficiency Scores

pHI: 0.152
hipred: N
hipred_score: 0.170
ghis: 0.418

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.770

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Slc34a3
Phenotype: renal/urinary system phenotype; skeleton phenotype; digestive/alimentary phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype;

Gene ontology

Biological process: sodium ion transport;phosphate ion transport;cellular phosphate ion homeostasis;sodium ion transmembrane transport;sodium-dependent phosphate transport
Cellular component: plasma membrane;brush border;integral component of membrane;apical plasma membrane;brush border membrane;vesicle
Molecular function: sodium:phosphate symporter activity;sodium-dependent phosphate transmembrane transporter activity