SLC4A3

solute carrier family 4 member 3, the group of Solute carrier family 4

Basic information

Region (hg38): 2:219627393-219641980

Links

ENSG00000114923 ∙ NCBI:6508 ∙ OMIM:106195 ∙ HGNC:11029 ∙ Uniprot:P48751 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• short QT syndrome 7 (Moderate), mode of inheritance: AD
• short QT syndrome (Moderate), mode of inheritance: AD
• short QT syndrome 7 (Strong), mode of inheritance: AD
• short QT syndrome (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Short QT syndrome 7	AD	Cardiovascular	The condition includes increased risk of arrhythmia, cardiomyopathy, and adverse cardiac outcomes, and identification may enable interventions	Cardiovascular	29167417

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC4A3 gene.

• Inborn genetic diseases (48 variants)
• not provided (21 variants)
• Short QT syndrome 7 (1 variants)
• SLC4A3-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC4A3 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				5	5	10
missense			48		2	50
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1	1	2
non coding					7	7
Total	0	0	48	5	14

Variants in SLC4A3

This is a list of pathogenic ClinVar variants found in the SLC4A3 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-219628015-C-T		Inborn genetic diseases	Uncertain significance (Feb 15, 2023)
2-219628020-G-A		Inborn genetic diseases	Uncertain significance (Nov 06, 2023)
2-219628426-C-A		Inborn genetic diseases	Uncertain significance (Dec 27, 2023)
2-219628427-C-G		Inborn genetic diseases	Uncertain significance (May 26, 2022)
2-219628499-A-G			Uncertain significance (-)
2-219628514-C-T			Benign (Dec 31, 2019)
2-219628553-G-A		Inborn genetic diseases	Uncertain significance (Jul 21, 2021)
2-219629139-C-T			Likely benign (Mar 01, 2023)
2-219629150-G-A		Inborn genetic diseases	Uncertain significance (Oct 16, 2023)
2-219629188-C-T		Inborn genetic diseases	Uncertain significance (May 31, 2023)
2-219629227-A-C		Inborn genetic diseases	Uncertain significance (Feb 21, 2024)
2-219629236-C-T		SLC4A3-related disorder	Likely benign (Dec 28, 2022)
2-219629278-C-T		Inborn genetic diseases	Uncertain significance (Aug 10, 2021)
2-219629286-C-T		SLC4A3-related disorder	Likely benign (Oct 01, 2023)
2-219629297-C-T			Uncertain significance (-)
2-219629314-G-C		Inborn genetic diseases	Uncertain significance (Dec 14, 2023)
2-219629320-G-A		Inborn genetic diseases	Uncertain significance (Jul 19, 2023)
2-219629390-C-G		Inborn genetic diseases	Uncertain significance (Dec 28, 2023)
2-219629390-C-T		Inborn genetic diseases	Uncertain significance (Jan 16, 2024)
2-219629392-C-A		Inborn genetic diseases	Uncertain significance (Jul 19, 2023)
2-219629395-C-T		Inborn genetic diseases	Uncertain significance (Nov 01, 2021)
2-219629625-A-G		Inborn genetic diseases	Uncertain significance (Dec 14, 2022)
2-219629653-C-T		Inborn genetic diseases	Uncertain significance (Apr 25, 2023)
2-219630109-G-A		Inborn genetic diseases	Uncertain significance (Dec 03, 2021)
2-219630127-C-T		Inborn genetic diseases	Likely benign (Jun 30, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC4A3	protein_coding	protein_coding	ENST00000373762	22	14654

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000123	1.00	125702	0	44	125746	0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.74	571	787	0.725	0.0000513	8031
Missense in Polyphen		206	354.34	0.58135		3574
Synonymous	0.690	327	343	0.953	0.0000226	2730
Loss of Function	4.25	18	50.7	0.355	0.00000285	548

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000393	0.000388
Ashkenazi Jewish	0.000205	0.000198
East Asian	0.000116	0.000109
Finnish	0.000233	0.000231
European (Non-Finnish)	0.000153	0.000149
Middle Eastern	0.000116	0.000109
South Asian	0.000197	0.000196
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plasma membrane anion exchange protein of wide distribution. Mediates at least a part of the Cl(-)/HCO3(-) exchange in cardiac myocytes. Both BAE3 and CAE3 forms transport Cl(-).
• Pathway: Transport of inorganic cations/anions and amino acids/oligopeptides;SLC-mediated transmembrane transport;Transport of small molecules;Bicarbonate transporters (Consensus)

Recessive Scores

• pRec: 0.296

Intolerance Scores

• rvis_EVS: -1.18
• rvis_percentile_EVS: 5.92

Haploinsufficiency Scores

• pHI: 0.138
• hipred: Y
• hipred_score: 0.685
• ghis: 0.466

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.842

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc4a3
• Phenotype: vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: slc4a3
• Affected structure: heart
• Phenotype tag: abnormal
• Phenotype quality: functionality

Gene ontology

• Biological process: inorganic anion transport;bicarbonate transport;regulation of intracellular pH;anion transmembrane transport
• Cellular component: plasma membrane;integral component of plasma membrane;membrane
• Molecular function: inorganic anion exchanger activity;anion:anion antiporter activity