SLC26A6

protein-coding

solute carrier family 26 member 6, the group of MicroRNA protein coding host genes|Solute carrier family 26

Gene summary

This gene belongs to the solute carrier 26 family, whose members encode anion transporter proteins. This particular family member encodes a protein involved in transporting chloride, oxalate, sulfate and bicarbonate. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Aug 2013]

MANE transcript

NM_022911.3

Inheritance

ClinVar variants

U:128B:20

Top phenotype

Hyperoxaluria

gnomAD constraint

pLI —, LoF o/e 0.65

Max pathogenic AF

—

Genomic locus

chr3:48,625,723-48,635,493

External References & Databases

Ensembl (ENSG00000225697)

Transcript & Mutation Effects

hg38 • Region Span ~9.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

primary hyperoxaluriaLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0002474

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLC26A6 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 122

not providedTotal: 16

HyperoxaluriaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_022911.3. 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			4 clinvar	3 clinvar	1 clinvar	8
missense			118 clinvar	15 clinvar	1 clinvar	134
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	128	18	2	148

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 84 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_022911.3	RefSeq	NP_075062.2	21	MANE Select
ENST00000395550.7	Ensembl	ENSP00000378920.2	21	MANE Select
NM_001040454.1	RefSeq	NP_001035544.1	20	Standard
NM_001281732.2	RefSeq	NP_001268661.1	20	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Mineral absorption - Homo sapiens (human)
Biopterin metabolism
Transport of inorganic cations/anions and amino acids/oligopeptides
SLC-mediated transmembrane transport
Transport of small molecules

Biological Process

ion transport
chloride transport
sulfate transport
bicarbonate transport
formate transport

Molecular Function

chloride channel activity
inorganic anion exchanger activity
secondary active sulfate transmembrane transporter activity
bicarbonate transmembrane transporter activity
chloride transmembrane transporter activity

Cellular Component

endoplasmic reticulum
plasma membrane
integral component of plasma membrane
vesicle membrane
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000395550
Coding exons: 21
Length: 9771
Individuals with no LoFs: 124746
Homozygous LoFs: 0
Heterozygous LoFs: 104
Defined: 124850
p: 0.000417

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.618	410	447	0.918	0.0000264	4873
Missense (PolyPhen)		123	145.12	0.84759		1609
Synonymous	-0.464	200	192	1.04	0.0000117	1600
Loss of Function	1.98	25	38.2	0.655	0.00000180	431

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00084	0.00084	rare
Latino/Admixed American	0.00046	0.00046	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.0015	0.0015	notable
Finnish	0	0.0	absent
European (Non-Finnish)	0.00032	0.00032	rare
South Asian	0.00033	0.00033	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Apical membrane anion-exchanger with wide epithelial distribution that plays a role as a component of the pH buffering system for maintaining acid-base homeostasis. Acts as a versatile DIDS-sensitive inorganic and organic anion transporter that mediates the uptake of monovalent anions like chloride, bicarbonate, formate and hydroxyl ion and divalent anions like sulfate and oxalate. Function in multiple exchange modes involving pairs of these anions, which include chloride-bicarbonate, chloride-oxalate, oxalate-formate, oxalate-sulfate and chloride- formate exchange. Apical membrane chloride-bicarbonate exchanger that mediates luminal chloride absorption and bicarbonate secretion by the small intestinal brush border membrane and contributes to intracellular pH regulation in the duodenal upper villous epithelium during proton-coupled peptide absorption, possibly by providing a bicarbonate import pathway. Mediates also intestinal chloride absorption and oxalate secretion, thereby preventing hyperoxaluria and calcium oxalate urolithiasis. Transepithelial oxalate secretion, chloride-formate, chloride- oxalate and chloride-bicarbonate transport activities in the duodenum are inhibited by PKC activation in a calcium-independent manner. The apical membrane chloride-bicarbonate exchanger provides also a major route for fluid and bicarbonate secretion into the proximal tubules of the kidney as well as into the proximal part of the interlobular pancreatic ductal tree, where it mediates electrogenic chloride-bicarbonate exchange with a chloride-bicarbonate stoichiometry of 1:2, and hence will dilute and alkalinize protein-rich acinar secretion. Mediates also the transcellular sulfate absorption and oxalate secretion across the apical membrane in the duodenum and the formate ion efflux at the apical brush border of cells in the proximal tubules of kidney. Plays a role in sperm capacitation by increasing intracellular pH.;

Recessive Scores

pRec: 0.245

Intolerance Scores

LoFtool: 0.0775
RVIS EVS: -0.06
RVIS percentile EVS: 48.84

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.140

Gene Damage Prediction

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