SLC34A3

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

Basic information

Region (hg38): 9:137230756-137236555

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

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 (437 variants)
• Autosomal recessive hypophosphatemic bone disease (130 variants)
• Inborn genetic diseases (52 variants)
• not specified (23 variants)
• SLC34A3-related condition (4 variants)
• Hypophosphatemic nephrolithiasis/osteoporosis 1 (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.

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			4	90	4	98
missense	5	3	176	15	5	204
nonsense	3	3	2			8
start loss			1			1
frameshift	15	4	2			21
inframe indel			8			8
splice donor/acceptor (+/-2bp)	2	12	1			15
splice region		1	10	8	3	22
non coding		1	9	52	16	78
Total	25	23	203	157	25

Highest pathogenic variant AF is 0.0000658

Variants in SLC34A3

This is a list of pathogenic ClinVar variants found in the SLC34A3 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-137231009-G-A			Uncertain significance (Jun 15, 2016)
9-137231570-C-T			Uncertain significance (Jun 15, 2016)
9-137231698-A-T		SLC34A3-related disorder	Likely benign (Mar 05, 2019)
9-137231704-T-C			Uncertain significance (May 20, 2023)
9-137231705-G-A			Uncertain significance (Dec 19, 2023)
9-137231707-C-T			Uncertain significance (Jul 06, 2022)
9-137231720-C-T		Autosomal recessive hypophosphatemic bone disease	Likely benign (Nov 04, 2023)
9-137231721-G-A			Uncertain significance (May 31, 2022)
9-137231740-C-T		Inborn genetic diseases	Uncertain significance (Sep 28, 2022)
9-137231741-C-A			Likely benign (Nov 30, 2022)
9-137231766-G-A			Uncertain significance (Apr 28, 2022)
9-137231770-A-G		Inborn genetic diseases	Likely benign (Aug 19, 2023)
9-137231783-T-C			Likely benign (Mar 08, 2023)
9-137231787-G-A			Uncertain significance (Mar 01, 2019)
9-137231794-G-T			Likely benign (Jan 14, 2024)
9-137231801-C-T			Likely benign (Oct 19, 2022)
9-137231805-G-A			Likely benign (Feb 20, 2023)
9-137231952-C-T			Likely benign (Dec 31, 2018)
9-137232076-C-G			Likely benign (Jul 28, 2023)
9-137232103-A-G			Likely benign (Aug 21, 2022)
9-137232106-G-C			Likely benign (Nov 16, 2020)
9-137232115-C-T			Likely benign (Jan 24, 2023)
9-137232126-T-A		Autosomal recessive hypophosphatemic bone disease	Uncertain significance (Jul 28, 2021)
9-137232126-TC-T			Pathogenic (Feb 08, 2019)
9-137232128-C-G		Inborn genetic diseases	Uncertain significance (Feb 05, 2024)

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