SLC26A8

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

Basic information

Region (hg38): 6:35943515-36024868

Links

ENSG00000112053 ∙ NCBI:116369 ∙ OMIM:608480 ∙ HGNC:14468 ∙ Uniprot:Q96RN1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• non-syndromic male infertility due to sperm motility disorder (Supportive), mode of inheritance: AR
• spermatogenic failure 3 (No Known Disease Relationship), mode of inheritance: AD
• spermatogenic failure 3 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spermatogenic failure 3	AD	General	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	Genitourinary	23582645

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC26A8 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC26A8 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				6	3	9
missense			41	9	8	58
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					2	2
non coding					17	17
Total	0	0	42	15	28

Variants in SLC26A8

This is a list of pathogenic ClinVar variants found in the SLC26A8 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-35943919-T-C		SLC26A8-related disorder	Likely benign (Sep 18, 2019)
6-35943953-G-A		Spermatogenic failure 3	Pathogenic (May 02, 2013)
6-35943983-G-T		not specified	Uncertain significance (Mar 07, 2024)
6-35943993-C-G		not specified	Uncertain significance (Mar 11, 2022)
6-35944012-G-A		not specified	Uncertain significance (Feb 22, 2023)
6-35944079-G-A			Benign (Mar 01, 2024)
6-35944132-G-A		not specified	Uncertain significance (Nov 03, 2023)
6-35944174-C-T		not specified	Likely benign (Sep 15, 2021)
6-35944200-C-G		SLC26A8-related disorder	Likely benign (Jun 12, 2019)
6-35944266-C-A		not specified	Uncertain significance (May 04, 2022)
6-35944295-G-T		not specified	Uncertain significance (Dec 22, 2023)
6-35944318-A-G		not specified	Uncertain significance (Aug 02, 2022)
6-35944325-A-G		not specified	Likely benign (Aug 03, 2022)
6-35944492-A-G			Benign (Jun 19, 2021)
6-35944509-AAATAAT-A			Benign (Nov 12, 2018)
6-35951188-C-T			Benign (Nov 20, 2018)
6-35951189-G-A		not specified	Uncertain significance (May 15, 2024)
6-35951201-C-T		Spermatogenic failure 3 • not specified	Conflicting classifications of pathogenicity (Dec 14, 2022)
6-35951210-C-T			Benign (Oct 25, 2018)
6-35951261-C-T		not specified	Uncertain significance (Feb 07, 2023)
6-35951478-C-T		not specified	Uncertain significance (May 24, 2023)
6-35951489-G-C		not specified	Uncertain significance (Apr 13, 2022)
6-35955178-A-G		not specified	Uncertain significance (May 16, 2024)
6-35955184-C-G		not specified	Uncertain significance (Jan 26, 2022)
6-35955184-C-T		SLC26A8-related disorder	Likely benign (Mar 27, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC26A8	protein_coding	protein_coding	ENST00000490799	19	81355

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.26e-12	0.983	125592	0	156	125748	0.000620

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.44	435	528	0.824	0.0000279	6381
Missense in Polyphen		112	147.96	0.75696		1922
Synonymous	1.17	186	207	0.897	0.0000125	1895
Loss of Function	2.41	25	41.8	0.598	0.00000219	482

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000827	0.000823
Ashkenazi Jewish	0.00	0.00
East Asian	0.000219	0.000217
Finnish	0.000140	0.000139
European (Non-Finnish)	0.00105	0.00104
Middle Eastern	0.000219	0.000217
South Asian	0.000238	0.000229
Other	0.00102	0.000978

dbNSFP

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.
• Pathway: Tenofovir/Adefovir Pathway, Pharmacodynamics;Tenofovir/Adefovir Pathway, Pharmacokinetics;Methionine and cysteine metabolism (Consensus)

Recessive Scores

• pRec: 0.106

Intolerance Scores

• loftool: 0.0430
• rvis_EVS: 0.69
• rvis_percentile_EVS: 85.29

Haploinsufficiency Scores

• pHI: 0.155
• hipred: N
• hipred_score: 0.271
• ghis: 0.437

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.543

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc26a8
• Phenotype: cellular phenotype; reproductive system phenotype

Gene ontology

• Biological process: anion transport;chloride transport;multicellular organism development;sulfate transport;bicarbonate transport;oxalate transport;flagellated sperm motility;sperm capacitation;meiotic cell cycle;sulfate transmembrane transport;chloride transmembrane transport
• Cellular component: plasma membrane;integral component of plasma membrane
• Molecular function: chloride channel activity;protein binding;secondary active sulfate transmembrane transporter activity;bicarbonate transmembrane transporter activity;chloride transmembrane transporter activity;sulfate transmembrane transporter activity;anion:anion antiporter activity;oxalate transmembrane transporter activity