GeneBe

SLC26A8

protein-coding

solute carrier family 26 member 8, the group of Solute carrier family 26

Gene summary

This gene encodes a member of the SLC26 gene family of anion transporters. Family members are well conserved in gene structure and protein length yet have markedly different tissue expression patterns. The expression of this gene appears to be restricted to spermatocytes. Alternatively spliced transcript variants that encode different isoforms have been described. [provided by RefSeq, Jul 2010]

MANE transcript

NM_052961.4

Inheritance

AR, AD

ClinVar variants

P:3U:115B:38

Top phenotype

Spermatogenic failure 3

gnomAD constraint

pLI —, LoF o/e 0.6

Max pathogenic AF

—

Genomic locus

chr6:35,943,516-36,024,868

External References & Databases

Ensembl (ENSG00000112053)NCBI Gene (116369)OMIM (608480)HGNC:14468GenCCUniProt (Q96RN1)AlphaFoldClinVar (SLC26A8)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~81.4 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

non-syndromic male infertility due to sperm motility disorderSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0017173

Submitter: Orphanet

spermatogenic failure 3LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0011720

Submitter: Labcorp Genetics (formerly Invitae)

spermatogenic failure 3NO_KNOWN

Inheritance Pattern: AD

Disease ID:MONDO:0011720

Submitter: Ambry Genetics

non-syndromic male infertility due to sperm motility disorderSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0017173

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Spermatogenic failure 3AD

Manifestation: Genitourinary

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 23582645Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLC26A8 variants in ClinVar

4 Conditions Cataloged
not specifiedTotal: 129
not providedTotal: 18
Spermatogenic failure 3Total: 12
SLC26A8-related disorderTotal: 10

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_052961.4. 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.

EffectPLPVUSLBBSum
synonymous
12
clinvar
2
clinvar
 14
missense
2
clinvar
111
clinvar
21
clinvar
3
clinvar
 137
nonsense
1
clinvar
 1
start loss
0
frameshift
1
clinvar
1
clinvar
 2
splice donor/acceptor (+/-2bp)
2
clinvar
 2
Total30115335156

Highest pathogenic variant AF is 0.00069042866

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_052961.4RefSeqNP_443193.119MANE Select
ENST00000490799.6EnsemblENSP00000417638.119MANE Select
NM_001193476.2RefSeqNP_001180405.119Standard
NM_138718.3RefSeqNP_619732.217Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Tenofovir/Adefovir Pathway, Pharmacodynamics
  • Tenofovir/Adefovir Pathway, Pharmacokinetics
  • Methionine and cysteine metabolism

Biological Process

  • anion transport
  • chloride transport
  • multicellular organism development
  • sulfate transport
  • bicarbonate transport

Molecular Function

  • chloride channel activity
  • protein binding
  • secondary active sulfate transmembrane transporter activity
  • bicarbonate transmembrane transporter activity
  • chloride transmembrane transporter activity

Cellular Component

  • plasma membrane
  • integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000490799
Coding exons
19
Length
81355
Individuals with no LoFs
125592
Homozygous LoFs
0
Heterozygous LoFs
156
Defined
125748
p
0.000620
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.444355280.8240.00002796381
Missense (PolyPhen)112147.960.756961922
Synonymous1.171862070.8970.00001251895
Loss of Function2.412541.80.5980.00000219482

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000560.00055rare
Latino/Admixed American0.000270.00026rare
Ashkenazi Jewish00.0absent
East Asian0.000220.00022rare
Finnish0.000140.00014rare
European (Non-Finnish)0.00100.0010notable
South Asian0.000240.00023rare
Other0.00100.00098notable

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Acts as a DIDS-sensitive anion exchanger mediating chloride, sulfate and oxalate transport. May fulfill critical anion exchange functions in male germ line during meiosis and hence may play a role in spermatogenesis. May be involved in a new regulatory pathway linking sulfate transport to RhoGTPase signaling in male germ cells. A critical component of the sperm annulus that is essential for correct sperm tail differentiation and motility and hence male fertility. May form a moleculer complex involved in the regulation of chloride and bicarbonate ions fluxes during sperm capacitation. {ECO:0000269|PubMed:11278976, ECO:0000269|PubMed:11834742, ECO:0000269|PubMed:22121115}.;
Disease
DISEASE: Spermatogenic failure 3 (SPGF3) [MIM:606766]: A disorder characterized by primary infertility, sperm morphologic abnormalities, and moderate to severe asthenozoospermia, condition in which the percentage of progressively motile sperm is abnormally low. {ECO:0000269|PubMed:23582645}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.106

Intolerance Scores

LoFtool
0.0430
RVIS EVS
0.69
RVIS percentile EVS
85.29

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
S
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.543

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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