SLC5A5

protein-coding

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

Gene summary

This gene encodes a member of the sodium glucose cotransporter family. The encoded protein is responsible for the uptake of iodine in tissues such as the thyroid and lactating breast tissue. The iodine taken up by the thyroid is incorporated into the metabolic regulators triiodothyronine (T3) and tetraiodothyronine (T4). Mutations in this gene are associated with thyroid dyshormonogenesis 1.[provided by RefSeq, Sep 2009]

MANE transcript

NM_000453.3

Inheritance

ClinVar variants

P:52U:94B:225

Top phenotype

Thyroid dyshormonogenesis 1

gnomAD constraint

pLI —, LoF o/e 0.33

Max pathogenic AF

—

Genomic locus

chr19:17,871,945-17,895,174

External References & Databases

Ensembl (ENSG00000105641)

Transcript & Mutation Effects

hg38 • Region Span ~23.2 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

familial thyroid dyshormonogenesisSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0010132

Submitter: Orphanet

thyroid dyshormonogenesis 1DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0020716

Submitter: G2P

thyroid dyshormonogenesis 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0020716

Submitter: Ambry Genetics

thyroid dyshormonogenesis 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0020716

Submitter: PanelApp Australia

thyroid dyshormonogenesis 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0020716

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Thyroid dyshormonogenesis 1AR

Manifestation: Endocrine; Oncologic

Intervention: Endocrine; Oncologic

Rationale: Medical treatment of hypothyroidism (eg, with T4) can be effective; Thyroid neoplasms have also been reported, and surveillance may be beneficial

Comments: Neoplasms have been reported as well as endocrine manifestations

Refs: 9171822; 19916865; 21543982; 21565787

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLC5A5 variants in ClinVar

7 Conditions Cataloged

not providedTotal: 400

Inborn genetic diseasesTotal: 73

Thyroid dyshormonogenesis 1Total: 71

not specifiedTotal: 25

SLC5A5-related disorderTotal: 20

congenital hypothyreodismTotal: 1

Congenital hypothyroidismTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000453.3. 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			3 clinvar	216 clinvar	2 clinvar	221
missense	4 clinvar	6 clinvar	90 clinvar	7 clinvar		107
nonsense	6 clinvar	2 clinvar				8
start loss						0
frameshift	9 clinvar	6 clinvar				15
splice donor/acceptor (+/-2bp)	1 clinvar	18 clinvar	1 clinvar			20
Total	20	32	94	223	2	371

Highest pathogenic variant AF is 0.000045726683

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000453.3	RefSeq	NP_000444.1	15	MANE Select
ENST00000222248.4	Ensembl	ENSP00000222248.2	15	MANE Select
NM_001440707.1	RefSeq	NP_001427636.1	15	Standard
ENST00001140674.1	Ensembl	ENSP00000801766.1	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Thyroid hormone synthesis - Homo sapiens (human)
Thyroid hormone synthesis
Thyroxine (Thyroid Hormone) Production
Nuclear Receptors Meta-Pathway
NRF2 pathway

Biological Process

thyroid hormone generation
ion transport
sodium ion transport
iodide transport
transmembrane transport

Molecular Function

sodium:iodide symporter activity
iodide transmembrane transporter activity

Cellular Component

nucleus
plasma membrane
integral component of membrane
extracellular exosome
extracellular vesicle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000222248
Coding exons: 15
Length: 23202
Individuals with no LoFs: 125705
Homozygous LoFs: 0
Heterozygous LoFs: 43
Defined: 125748
p: 0.000171

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.918	336	387	0.869	0.0000254	4015
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00046	0.00046	rare
Ashkenazi Jewish	0.00011	0.000099	rare
East Asian	0.00065	0.00065	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000064	0.000062	rare
South Asian	0.00017	0.00016	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Mediates iodide uptake in the thyroid gland.;

Intolerance Scores

LoFtool: 0.109
RVIS EVS: -0.89
RVIS percentile EVS: 10.43

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.248

Gene Damage Prediction

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