IYD

iodotyrosine deiodinase

Basic information

Region (hg38): 6:150368892-150405969

Previous symbols: [ "C6orf71" ]

Links

ENSG00000009765

∙ NCBI:389434 ∙ OMIM:612025 ∙ HGNC:21071 ∙ Uniprot:Q6PHW0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

thyroid dyshormonogenesis 4 (Strong), mode of inheritance: AR
familial thyroid dyshormonogenesis (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Thyroid dyshormonogenesis 4	AR	Endocrine	Individuals may present with clinical signs and sequelae of childhood hypothyroidism, which can lead to long-term neurologic and other effects, and medical treatment of hypothyroidism (eg, with T4) can be beneficial	Endocrine	18765512; 18434651; 22535972
In heterozygotes, clinical hypothyroidism has been described as arising at a later age than in individuals with biallelic variants

ClinVar

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

not_specified (51 variants)
not_provided (20 variants)
IYD-related_disorder (11 variants)
Iodotyrosine_deiodination_defect (11 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IYD gene is commonly pathogenic or not. These statistics are base on transcript: NM_000203395.3. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	10 clinvar		11
missense	1 clinvar	3 clinvar	42 clinvar	5 clinvar	4 clinvar	55
nonsense		1 clinvar				1
start loss						0
frameshift		4 clinvar				4
splice donor/acceptor (+/-2bp)						0
Total	1	8	43	15	4

Highest pathogenic variant AF is 0.000249694

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IYD	protein_coding	protein_coding	ENST00000229447	6	37078

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00408	0.964	125726	0	22	125748	0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.243	153	162	0.946	0.00000897	1948
Missense in Polyphen		39	44.577	0.87489		558
Synonymous	0.313	56	59.1	0.948	0.00000356	525
Loss of Function	1.87	6	13.4	0.448	6.39e-7	163

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000615	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000141	0.000141
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000327	0.0000327
Other	0.000490	0.000489

dbNSFP

Source: dbNSFP

Function: FUNCTION: Catalyzes the oxidative NADPH-dependent deiodination of monoiodotyrosine (L-MIT) or diiodotyrosine (L-DIT) (PubMed:15289438, PubMed:25395621, PubMed:18434651). Acts during the hydrolysis of thyroglobulin to liberate iodide, which can then reenter the hormone-producing pathways (PubMed:18434651). Acts more efficiently on monoiodotyrosine than on diiodotyrosine (PubMed:15289438). {ECO:0000269|PubMed:15289438, ECO:0000269|PubMed:18434651, ECO:0000269|PubMed:25395621}.;
Pathway: Thyroid hormone synthesis - Homo sapiens (human);Metabolism of amino acids and derivatives;Metabolism;Thyroxine biosynthesis;Amine-derived hormones (Consensus)

Recessive Scores

pRec: 0.167

Intolerance Scores

loftool: 0.287
rvis_EVS: 2
rvis_percentile_EVS: 97.66

Haploinsufficiency Scores

pHI: 0.0932
hipred: N
hipred_score: 0.396
ghis: 0.402

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.0193

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Iyd
Phenotype

Gene ontology

Biological process: tyrosine metabolic process;thyroid hormone generation;thyroid hormone metabolic process;oxidation-reduction process;cellular oxidant detoxification
Cellular component: nucleoplasm;plasma membrane;integral component of plasma membrane;cytoplasmic vesicle membrane
Molecular function: iodide peroxidase activity;protein binding;FMN binding;oxidoreductase activity