SLC5A5

solute carrier family 5 member 5, the group of Solute carrier family 5

Basic information

Region (hg38): 19:17871945-17895174

Links

ENSG00000105641 ∙ NCBI:6528 ∙ OMIM:601843 ∙ HGNC:11040 ∙ Uniprot:Q92911 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• thyroid dyshormonogenesis 1 (Definitive), mode of inheritance: AR
• thyroid dyshormonogenesis 1 (Strong), mode of inheritance: AR
• familial thyroid dyshormonogenesis (Supportive), mode of inheritance: AR
• thyroid dyshormonogenesis 1 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Thyroid dyshormonogenesis 1	AR	Endocrine; Oncologic	Medical treatment of hypothyroidism (eg, with T4) can be effective; Thyroid neoplasms have also been reported, and surveillance may be beneficial	Endocrine; Oncologic	9171822; 19916865; 21543982; 21565787
Neoplasms have been reported as well as endocrine manifestations

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC5A5 gene.

• not_provided (398 variants)
• Thyroid_dyshormonogenesis_1 (70 variants)
• Inborn_genetic_diseases (65 variants)
• SLC5A5-related_disorder (13 variants)
• not_specified (13 variants)
• congenital_hypothyreodism (1 variants)
• Congenital_hypothyroidism (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC5A5 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000453.3. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	214	2	218
missense	4	7	76	7		94
nonsense	5	1				6
start loss						0
frameshift	9	8				17
splice donor/acceptor (+/-2bp)	1	16				17
Total	19	32	78	221	2

Highest pathogenic variant AF is 0.0000457267

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC5A5	protein_coding	protein_coding	ENST00000222248	15	23202

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00295	0.997	125705	0	43	125748	0.000171

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.918	336	387	0.869	0.0000254	4015
Missense in Polyphen		120	154.08	0.77881		1652
Synonymous	-0.955	196	180	1.09	0.0000130	1425
Loss of Function	3.39	10	30.1	0.333	0.00000141	322

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000463	0.000463
Ashkenazi Jewish	0.000111	0.0000992
East Asian	0.000653	0.000653
Finnish	0.00	0.00
European (Non-Finnish)	0.0000640	0.0000615
Middle Eastern	0.000653	0.000653
South Asian	0.000166	0.000163
Other	0.000333	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Mediates iodide uptake in the thyroid gland.
• Pathway: Thyroid hormone synthesis - Homo sapiens (human);Thyroid hormone synthesis;Thyroxine (Thyroid Hormone) Production;Nuclear Receptors Meta-Pathway;NRF2 pathway;Metabolism of amino acids and derivatives;Tyrosine metabolism;Purine metabolism;Metabolism;Organic anion transporters;Amino acid and oligopeptide SLC transporters;Transport of inorganic cations/anions and amino acids/oligopeptides;SLC-mediated transmembrane transport;Transport of small molecules;EGFR1;Thyroxine biosynthesis;Amine-derived hormones (Consensus)

Intolerance Scores

• loftool: 0.109
• rvis_EVS: -0.89
• rvis_percentile_EVS: 10.43

Haploinsufficiency Scores

• pHI: 0.0675
• hipred: Y
• hipred_score: 0.591
• ghis: 0.483

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.248

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc5a5
• Phenotype: homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: thyroid hormone generation;ion transport;sodium ion transport;iodide transport;transmembrane transport;cellular response to cAMP;cellular response to gonadotropin stimulus
• Cellular component: nucleus;plasma membrane;integral component of membrane;extracellular exosome;extracellular vesicle
• Molecular function: sodium:iodide symporter activity;iodide transmembrane transporter activity