IYD

iodotyrosine deiodinase

Basic information

Region (hg38): 6:150368891-150405969

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.

• Iodotyrosine deiodination defect (1 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.

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				9		9
missense	1	2	25	6	8	42
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			7	2	16	25
Total	1	2	33	17	24

Highest pathogenic variant AF is 0.00000657

Variants in IYD

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

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

Position	Type	Phenotype	Significance	ClinVar
6-150368928-T-A		Congenital hypothyroidism	Uncertain significance (Jun 14, 2016)
6-150369060-C-T		not specified	Uncertain significance (Dec 15, 2023)
6-150369063-T-C		not specified	Uncertain significance (Jun 30, 2023)
6-150369091-T-C			Likely benign (Sep 12, 2018)
6-150369100-C-G		IYD-related disorder	Likely benign (May 01, 2019)
6-150369116-A-G		not specified	Uncertain significance (Nov 07, 2023)
6-150369121-G-A			Benign/Likely benign (Mar 01, 2023)
6-150369146-G-A		not specified	Uncertain significance (Aug 12, 2021)
6-150369154-C-G			Likely benign (May 01, 2023)
6-150389311-G-A			Benign (Nov 12, 2018)
6-150389354-G-A			Benign (Jul 01, 2023)
6-150389380-A-C		not specified	Uncertain significance (Sep 26, 2022)
6-150389383-T-C			Likely benign (Jan 03, 2018)
6-150389412-A-C			Likely benign (Sep 09, 2018)
6-150389421-A-T		not specified	Uncertain significance (Jan 03, 2022)
6-150389441-T-C		not specified	Uncertain significance (Apr 12, 2022)
6-150389459-C-T		IYD-related disorder	Likely benign (Sep 22, 2023)
6-150389474-C-T		Iodotyrosine deiodination defect • IYD-related disorder	Likely pathogenic (Mar 02, 2023)
6-150389486-TTCA-T		Iodotyrosine deiodination defect • IYD-related disorder • not specified	Conflicting classifications of pathogenicity (Feb 13, 2023)
6-150389496-A-G		Iodotyrosine deiodination defect	Benign (May 04, 2022)
6-150389500-G-A			Likely benign (Nov 16, 2018)
6-150389510-A-G		not specified	Uncertain significance (Sep 27, 2022)
6-150389513-G-C		not specified	Uncertain significance (Sep 17, 2021)
6-150389520-T-C		Iodotyrosine deiodination defect	Likely pathogenic (Apr 05, 2024)
6-150389522-G-A		not specified	Uncertain significance (Mar 15, 2021)

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

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