IYD

Summary

IYD (iodotyrosine deiodinase, HGNC:21071) is a protein-coding gene on chromosome 6q25.1, encoding Iodotyrosine deiodinase 1 (Q6PHW0). Catalyzes the dehalogenation of halotyrosines such as 3-bromo-L-tyrosine, 3-chloro-L-tyrosine, 3-iodo-L-tyrosine and 3,5-diiodo-L-tyrosine.

This gene encodes an enzyme that catalyzes the oxidative NADPH-dependent deiodination of mono- and diiodotyrosine, which are the halogenated byproducts of thyroid hormone production. The N-terminus of the protein functions as a membrane anchor. Mutations in this gene cause congenital hypothyroidism due to dyshormonogenesis type 4, which is also referred to as deiodinase deficiency, or iodotyrosine dehalogenase deficiency, or thyroid hormonogenesis type 4. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 389434 — RefSeq curated summary.

At a glance

• Gene–disease (curated): thyroid dyshormonogenesis 4 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 111 total — 6 likely-pathogenic
• Phenotypes (HPO): 33
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_203395

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21071
Approved symbol	IYD
Name	iodotyrosine deiodinase
Location	6q25.1
Locus type	gene with protein product
Status	Approved
Aliases	dJ422F24.1, DEHAL1
Ensembl gene	ENSG00000009765
Ensembl biotype	protein_coding
OMIM	612025
Entrez	389434

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000229447, ENST00000344419, ENST00000367335, ENST00000392255, ENST00000392256, ENST00000422583, ENST00000425615, ENST00000500320, ENST00000546121, ENST00000892602, ENST00000892603

RefSeq mRNA: 4 — MANE Select: NM_203395 NM_001164694, NM_001164695, NM_001318495, NM_203395

CCDS: CCDS5227, CCDS55066, CCDS55067

Canonical transcript exons

ENST00000344419 — 5 exons

Exon	Start	End
ENSE00000000151	150369012	150369209
ENSE00001128693	150389352	150389543
ENSE00002321567	150398055	150405969
ENSE00003641162	150394099	150394255
ENSE00003649524	150392345	150392504

Expression profiles

Bgee: expression breadth ubiquitous, 130 present calls, max score 99.23.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.8926 / max 1268.8696, expressed in 57 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
70518	1.1418	51
70519	0.6885	24
70516	0.0541	6
70517	0.0082	3

Top tissues by expression

239 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of thyroid gland	UBERON:0001119	99.23	gold quality
thyroid gland	UBERON:0002046	98.98	gold quality
left lobe of thyroid gland	UBERON:0001120	98.97	gold quality
jejunal mucosa	UBERON:0000399	89.73	silver quality
gall bladder	UBERON:0002110	83.59	gold quality
duodenum	UBERON:0002114	83.08	gold quality
rectum	UBERON:0001052	79.78	gold quality
liver	UBERON:0002107	79.22	gold quality
right lobe of liver	UBERON:0001114	78.71	gold quality
adult mammalian kidney	UBERON:0000082	75.57	gold quality
mucosa of transverse colon	UBERON:0004991	75.27	gold quality
ileal mucosa	UBERON:0000331	72.66	gold quality
small intestine	UBERON:0002108	71.69	gold quality
kidney	UBERON:0002113	71.14	gold quality
small intestine Peyer’s patch	UBERON:0003454	70.62	gold quality
jejunum	UBERON:0002115	67.67	silver quality
mucosa of sigmoid colon	UBERON:0004993	67.27	silver quality
colonic mucosa	UBERON:0000317	66.48	gold quality
transverse colon	UBERON:0001157	66.02	gold quality
cortex of kidney	UBERON:0001225	65.81	gold quality
kidney epithelium	UBERON:0004819	64.14	gold quality
intestine	UBERON:0000160	62.12	gold quality
vermiform appendix	UBERON:0001154	61.42	gold quality
lower lobe of lung	UBERON:0008949	58.88	silver quality
large intestine	UBERON:0000059	58.68	gold quality
colonic epithelium	UBERON:0000397	58.28	gold quality
colon	UBERON:0001155	58.04	gold quality
amniotic fluid	UBERON:0000173	57.79	silver quality
islet of Langerhans	UBERON:0000006	57.20	gold quality
caecum	UBERON:0001153	56.78	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.91
E-MTAB-5061	no	2.21

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

182 targeting IYD, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 12)

• molecular cloning and investigation of the localization and activity of DEHAL1 (PMID:15289438)
• the cytoplasmic tail of DEHAL1 could play a role in the stability of the protein (PMID:16910871)
• Diffuse cytoplasmatic localisation or downregulation of DEHAL1 expression in thyroid cancers suggests alteration or loss of DEHAL1 function during thyroid cell dedifferentiation. (PMID:17322488)
• homozygous mutations in DEHAL1 appear to cause human iodotyrosine deiodinase deficiency, leading to hereditary hypothyroidism and goiter (PMID:18434651)
• This study describes a functional mutation within IYD, demonstrating the molecular basis of the iodine wasting form of congenital hypothyroidism (PMID:18765512)
• Mutations in DEHAL1 leads to hypothyroidism, goiter and mental retardation (Review) (PMID:20298747)
• high activity of human saliva peroxidase with iodide as a substrate may play a crucial role in the bioavailability and metabolism of biologically active iodide. (PMID:21870604)
• Iodotyrosine deiodinase defect identified via genome-wide approach. (PMID:22535972)
• A switch between one- and two-electron chemistry of iodotyrosine deiodinase is controlled by substrate. (PMID:25395621)
• The rate-limiting processes that contribute to the ability of flavin to promote reductive dehalogenation in human IYD. (PMID:26151430)
• Redox control of iodotyrosine deiodinase. (PMID:30052294)
• Congenital Hypothyroidism in Two Sudanese Families Harboring a Novel Iodotyrosine Deiodinase Mutation (IYD R279C). (PMID:36633921)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	iyd	ENSDARG00000076056
mus_musculus	Iyd	ENSMUSG00000019762
rattus_norvegicus	Iyd	ENSRNOG00000016286
drosophila_melanogaster	Iyd	FBGN0286980
caenorhabditis_elegans		WBGENE00015334

Protein

Protein identifiers

Iodotyrosine deiodinase 1 — Q6PHW0 (reviewed: Q6PHW0)

Alternative names: Iodotyrosine dehalogenase 1

All UniProt accessions (5): Q6PHW0, C9JXJ9, F5H543, F6VN83, H7C0X6

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the dehalogenation of halotyrosines such as 3-bromo-L-tyrosine, 3-chloro-L-tyrosine, 3-iodo-L-tyrosine and 3,5-diiodo-L-tyrosine. During thyroid hormone biosynthesis, facilitates iodide salvage by catalysing the oxidative NADPH-dependent deiodination of the halogenated by-products of thyroid hormone production, monoiodotyrosine (L-MIT) and diiodotyrosine (L-DIT). The scavanged iodide can then reenter the hormone-producing pathways. Acts more efficiently on 3-iodo-L-tyrosine than 3,5-diiodo-L-tyrosine.

Subunit / interactions. Homodimer.

Subcellular location. Cell membrane. Cytoplasmic vesicle membrane.

Tissue specificity. Expressed at a high level in thyroid gland (at protein level). Expressed at a high level in thyroid gland and at lower level in kidney and trachea.

Disease relevance. Thyroid dyshormonogenesis 4 (TDH4) [MIM:274800] A disorder due to thyroid dyshormonogenesis, causing severe hypothyroidism, goiter, excessive levels of iodotyrosine in serum and urine, and variable mental deficits derived from unrecognized and untreated hypothyroidism. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the nitroreductase family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q6PHW0-1	1	yes
Q6PHW0-3	3, E
Q6PHW0-4	4, B
Q6PHW0-5	5, C
Q6PHW0-6	6, D
Q6PHW0-7	7, F

RefSeq proteins (4): NP_001158166, NP_001158167, NP_001305424, NP_981932* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000415	Nitroreductase-like	Homologous_superfamily
IPR029479	Nitroreductase	Domain
IPR050627	Nitroreductase/BluB	Family

Pfam: PF00881

Enzyme classification (BRENDA):

• EC 1.21.1.1 — iodotyrosine deiodinase (BRENDA: 15 organisms, 36 substrates, 130 inhibitors, 42 Km, 34 kcat entries)

Substrate kinetics (BRENDA)

6 substrates with measured Km, best-characterized 6. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
3-IODO-L-TYROSINE	0.0002–15	20
3,5-DIIODO-L-TYROSINE	0.0011–0.44	8
2-IODOPHENOL	2.9–6.6	7
3-BROMO-L-TYROSINE	0.0001–0.008	2
3-CHLORO-L-TYROSINE	0.005–0.021	2
NADPH	0.027	1

Catalyzed reactions (Rhea), 5 shown:

• iodide + L-tyrosine + NADP(+) = 3-iodo-L-tyrosine + NADPH (RHEA:27453)
• 3-iodo-L-tyrosine + iodide + NADP(+) = 3,5-diiodo-L-tyrosine + NADPH + H(+) (RHEA:27457)
• 2 iodide + L-tyrosine + 2 NADP(+) = 3,5-diiodo-L-tyrosine + 2 NADPH + H(+) (RHEA:32479)
• L-tyrosine + chloride + NADP(+) = 3-chloro-L-tyrosine + NADPH (RHEA:70343)
• bromide + L-tyrosine + NADP(+) = 3-bromo-L-tyrosine + NADPH (RHEA:70347)

UniProt features (52 total): helix 10, binding site 9, splice variant 9, strand 8, sequence variant 5, mutagenesis site 5, compositionally biased region 2, chain 1, transmembrane region 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
5YAK	X-RAY DIFFRACTION	2.3
4TTB	X-RAY DIFFRACTION	2.45
4TTC	X-RAY DIFFRACTION	2.65

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6PHW0-F1	87.92	0.68

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (9): 161; 182; 237–239; 279; 100–104; 128–129; 128; 130; 157

Mutagenesis-validated functional residues (5):

Position	Phenotype
101	strongly reduces activity.
101	reduces activity.
105	activity as the wild type.
116	activity as the wild type.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-209968	Thyroxine biosynthesis
R-HSA-1430728	Metabolism
R-HSA-209776	Metabolism of amine-derived hormones
R-HSA-71291	Metabolism of amino acids and derivatives

MSigDB gene sets: 163 (showing top): GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_THYROID_HORMONE_METABOLIC_PROCESS, COUP_01, chr6q25, GOBP_AROMATIC_AMINO_ACID_METABOLIC_PROCESS, HNF4_DR1_Q3, HNF4_01, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOBP_MODIFIED_AMINO_ACID_METABOLIC_PROCESS, GOMF_FMN_BINDING, ZHOU_INFLAMMATORY_RESPONSE_LIVE_UP, DODD_NASOPHARYNGEAL_CARCINOMA_DN, OHGUCHI_LIVER_HNF4A_TARGETS_DN

GO Biological Process (2): obsolete tyrosine metabolic process (GO:0006570), thyroid hormone metabolic process (GO:0042403)

GO Molecular Function (4): FMN binding (GO:0010181), oxidoreductase activity (GO:0016491), iodotyrosine deiodinase activity (GO:0140616), protein binding (GO:0005515)

GO Cellular Component (5): nucleoplasm (GO:0005654), plasma membrane (GO:0005886), cytoplasmic vesicle membrane (GO:0030659), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Metabolism of amine-derived hormones	1
Metabolism of amino acids and derivatives	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
modified amino acid metabolic process	1
phenol-containing compound metabolic process	1
hormone metabolic process	1
ribonucleotide binding	1
anion binding	1
catalytic activity	1
oxidoreductase activity, acting on X-H and Y-H to form an X-Y bond	1
binding	1
nuclear lumen	1
membrane	1
cell periphery	1
vesicle membrane	1
cytoplasmic vesicle	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

2084 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IYD	DUOXA2	Q1HG44	952
IYD	DUOX2	Q9NRD8	929
IYD	SLC5A5	Q92911	917
IYD	SLC26A4	O43511	908
IYD	TPO	P07202	847
IYD	BLVRB	P30043	820
IYD	FOXE1	O00358	708
IYD	TSHR	P16473	708
IYD	TG	P01266	692
IYD	SLC26A7	Q8TE54	659
IYD	DUOXA1	Q1HG43	618
IYD	PAX8	Q06710	608
IYD	PPP1R14C	Q8TAE6	591
IYD	NKX2-1	P43699	577
IYD	PLEKHG1	Q9ULL1	564

IntAct

10 interactions, top by confidence:

A	B	Type	Score
TRIM69	IYD	psi-mi:“MI:0915”(physical association)	0.560
IYD	TRIM69	psi-mi:“MI:0915”(physical association)	0.560
IYD	H2BC12L	psi-mi:“MI:0915”(physical association)	0.400
IYD	H2BC21	psi-mi:“MI:0915”(physical association)	0.400
IYD	DDRGK1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (10): IYD (Two-hybrid), IYD (Affinity Capture-RNA), DDRGK1 (Affinity Capture-MS), TRIM69 (Two-hybrid), DDRGK1 (Affinity Capture-MS), IYD (Proximity Label-MS), IYD (Proximity Label-MS), IYD (Affinity Capture-MS), IYD (Affinity Capture-MS), IYD (Negative Genetic)

ESM2 similar proteins: A6T4R5, A7MGP2, A7S5D9, A7ZHK9, A7ZW69, A8ALG9, A9MPN4, A9MZR1, B1IQM0, B1LGS1, B1XC95, B2U2W9, B4SU90, B4TJD1, B4TXL6, B5RHA4, B5YZF5, B7LFY7, B7LVY2, B7M161, B7MBA3, B7MNY2, B7N7Z0, B7NI80, B7UIG8, C0Q5M6, C4ZRL3, E1JIB2, E7FDV5, E9FR69, F4KU78, P0A7F6, P0A7F7, P0A7F8, P34273, Q0T880, Q0TLL4, Q1RG71, Q326B6, Q32K91

Diamond homologs: A1KNR4, A5U7T6, A7S5D9, B9K712, C1AH36, E1JIB2, E7FDV5, E9FR69, F4KU78, O26223, P34273, P9WP78, P9WP79, Q5BK17, Q5REW1, Q6PHW0, Q6TA49, Q7TWV3, Q9DCX8, T2MBC4, P96707, A0R6D0, Q9CCK2, O28017, P0DX42, O25608, O30013, P45244, Q5HLA1, Q5XCB9, Q8CN23, Q8GED9, P58792, P81102, Q55233, Q60049

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
IYD	“down-regulates quantity”	3-iodo-L-tyrosine	“chemical modification”
IYD	“up-regulates quantity”	“L-tyrosine zwitterion”	“chemical modification”
IYD	“up-regulates quantity”	iodide	“chemical modification”
IYD	“down-regulates quantity”	3,5-diiodo-L-tyrosine	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

111 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	6
Uncertain significance	51
Likely benign	22
Benign	23

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
3593218	NM_203395.3(IYD):c.293_306del (p.Asn98fs)	Likely pathogenic
3593219	NM_203395.3(IYD):c.523_524insTT (p.Lys175fs)	Likely pathogenic
3593220	NM_203395.3(IYD):c.567del (p.Ile190fs)	Likely pathogenic
3593221	NM_203395.3(IYD):c.736C>T (p.Arg246Ter)	Likely pathogenic
737	NM_203395.3(IYD):c.301C>T (p.Arg101Trp)	Likely pathogenic
739	NM_203395.3(IYD):c.347T>C (p.Ile116Thr)	Likely pathogenic

SpliceAI

1354 predictions. Top by Δscore:

Variant	Effect	Δscore
6:150394094:CACA:C	acceptor_loss	1.0000
6:150394096:C:G	acceptor_gain	1.0000
6:150394096:CA:C	acceptor_loss	1.0000
6:150394097:A:AG	acceptor_gain	1.0000
6:150394097:A:AT	acceptor_loss	1.0000
6:150394098:G:A	acceptor_loss	1.0000
6:150394098:G:GT	acceptor_gain	1.0000
6:150394098:GA:G	acceptor_gain	1.0000
6:150394098:GAA:G	acceptor_gain	1.0000
6:150394098:GAAC:G	acceptor_gain	1.0000
6:150394098:GAACC:G	acceptor_gain	1.0000
6:150394254:AGG:A	donor_loss	1.0000
6:150394256:G:GC	donor_loss	1.0000
6:150394257:T:G	donor_loss	1.0000
6:150398232:GT:G	donor_gain	1.0000
6:150369206:GAAG:G	donor_gain	0.9900
6:150369206:GAAGG:G	donor_loss	0.9900
6:150369207:AAG:A	donor_loss	0.9900
6:150369208:AGGTA:A	donor_loss	0.9900
6:150369209:GGT:G	donor_loss	0.9900
6:150369210:GTAA:G	donor_loss	0.9900
6:150369211:T:G	donor_loss	0.9900
6:150389433:TTAAG:T	donor_gain	0.9900
6:150389485:GTTCA:G	donor_gain	0.9900
6:150389486:TTCAT:T	donor_gain	0.9900
6:150392328:AAT:A	acceptor_gain	0.9900
6:150392330:T:TA	acceptor_gain	0.9900
6:150392336:G:A	acceptor_gain	0.9900
6:150392387:T:TA	acceptor_gain	0.9900
6:150392500:CTGAG:C	donor_loss	0.9900

AlphaMissense

1918 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:150392356:A:C	S128R	0.997
6:150392358:T:A	S128R	0.997
6:150392358:T:G	S128R	0.997
6:150394214:A:C	S216R	0.997
6:150394216:T:A	S216R	0.997
6:150394216:T:G	S216R	0.997
6:150392377:T:A	W135R	0.996
6:150392377:T:C	W135R	0.996
6:150394114:A:C	K182N	0.993
6:150394114:A:T	K182N	0.993
6:150392479:T:A	W169R	0.990
6:150392479:T:C	W169R	0.990
6:150392481:G:C	W169C	0.990
6:150392481:G:T	W169C	0.990
6:150394113:A:T	K182I	0.990
6:150389473:A:C	R100S	0.989
6:150389473:A:T	R100S	0.989
6:150392423:G:C	R150P	0.988
6:150392351:C:A	A126D	0.986
6:150394233:G:A	G222D	0.985
6:150398164:G:A	G266E	0.985
6:150389475:G:C	R101P	0.983
6:150398202:C:A	R279S	0.983
6:150392454:C:A	N160K	0.982
6:150392454:C:G	N160K	0.982
6:150389472:G:C	R100T	0.981
6:150392444:A:T	E157V	0.981
6:150398065:T:C	L233P	0.981
6:150398155:T:C	L263P	0.981
6:150394239:T:C	L224P	0.980

dbSNP variants (sampled 300 via entrez): RS1000008153 (6:150402605 G>A,T), RS1000016405 (6:150404107 C>T), RS1000176537 (6:150375476 G>A), RS1000203044 (6:150378025 C>G,T), RS1000255456 (6:150386707 T>A,C), RS1000414924 (6:150380604 C>T), RS1000455981 (6:150398206 A>C,G), RS1000492658 (6:150404302 T>A), RS1000603658 (6:150370570 G>A,T), RS1000683770 (6:150371956 T>C,G), RS1000915767 (6:150370808 G>A), RS1000946646 (6:150376971 C>G,T), RS1001131516 (6:150393751 G>A), RS1001263183 (6:150370442 T>A), RS1001376675 (6:150404948 G>A,C)

Disease associations

OMIM: gene MIM:612025 | disease phenotypes: MIM:274800

GenCC curated gene-disease

Disease	Classification	Inheritance
thyroid dyshormonogenesis 4	Strong	Autosomal recessive
familial thyroid dyshormonogenesis	Supportive	Autosomal recessive

Mondo (2): thyroid dyshormonogenesis 4 (MONDO:0010136), familial thyroid dyshormonogenesis (MONDO:0010132)

Orphanet (1): Familial thyroid dyshormonogenesis (Orphanet:95716)

HPO phenotypes

33 total (30 of 33 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000158	Macroglossia
HP:0000270	Delayed cranial suture closure
HP:0000282	Facial edema
HP:0000407	Sensorineural hearing impairment
HP:0000821	Hypothyroidism
HP:0000851	Congenital hypothyroidism
HP:0000853	Goiter
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001254	Lethargy
HP:0001265	Hyporeflexia
HP:0001510	Growth delay
HP:0001537	Umbilical hernia
HP:0001662	Bradycardia
HP:0002019	Constipation
HP:0002045	Hypothermia
HP:0002925	Elevated circulating thyroid-stimulating hormone concentration
HP:0003265	Neonatal hyperbilirubinemia
HP:0004491	Large posterior fontanelle
HP:0005280	Depressed nasal bridge
HP:0005930	Abnormal epiphysis morphology
HP:0006579	Prolonged neonatal jaundice
HP:0008263	Thyroid defect in oxidation and organification of iodide
HP:0008828	Delayed proximal femoral epiphyseal ossification
HP:0008872	Feeding difficulties in infancy
HP:0011437	Maternal autoimmune disease
HP:0012758	Neurodevelopmental delay
HP:0025482	Positive perchlorate discharge test
HP:0025483	Abnormal circulating thyroglobulin concentration

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST000274_9	Metabolite levels	1.000000e-07
GCST002324_7	Anger	2.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004998	carbohydrate measurement
EFO:0003015	aggressive behavior

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C564766	Thyroid Dyshormonogenesis 1 (supp.)
C562770	Thyroid Dyshormonogenesis 4 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Thyroid hormone turnover

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2S)-2-amino-3-(4-hydroxy-3-iodophenyl)propanoic acid	1802488: IYD Binding Assay from Article 10.1021/acs.biochem.6b01308: “Active Site Binding Is Not Sufficient for Reductive Deiodination by Iodotyrosine Deiodinase.”	kd	0.0900	uM

CTD chemical–gene interactions

107 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation, increases methylation	2
Eosine I Bluish	decreases reaction, increases metabolic processing, decreases activity	2
Triclosan	decreases reaction, increases metabolic processing, decreases activity	2
dodecylbenzenesulfonic acid	decreases reaction, increases metabolic processing	1
cetyl sulfate	decreases reaction, increases metabolic processing	1
3-nitrotyrosine	decreases reaction, increases metabolic processing	1
3,3’,4’,5-tetrachlorosalicylanilide	decreases reaction, increases metabolic processing	1
tribromsalan	decreases reaction, increases metabolic processing	1
methylbenzethonium chloride	decreases reaction, increases metabolic processing	1
methyleugenol	decreases expression	1
methyl linoleate	decreases reaction, increases metabolic processing	1
Allura Red AC Dye	decreases reaction, increases metabolic processing	1
monoolein	decreases reaction, increases metabolic processing	1
brilliant blue	decreases reaction, increases metabolic processing	1
dexon (fungicide), sodium salt	increases metabolic processing, decreases reaction	1
dichlone	decreases reaction, increases metabolic processing	1
di-2-(ethylhexyl)phosphoric acid	decreases reaction, increases metabolic processing	1
dinocap	decreases reaction, increases metabolic processing	1
Fast Green FCF	decreases reaction, increases metabolic processing	1
lauryl gallate	decreases reaction, increases metabolic processing	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	increases metabolic processing, decreases reaction	1
morin	decreases reaction, increases metabolic processing	1
tetradecyltrimethylammonium	decreases reaction, increases metabolic processing	1
2,4,5-trichlorophenol	decreases reaction, increases metabolic processing	1
fluorophene	decreases reaction, increases metabolic processing	1
octyl gallate	decreases reaction, increases metabolic processing	1
sodium arsenite	decreases expression	1
2,2’-dihydroxy-6,6’-dinaphthyldisulfide	increases metabolic processing, decreases reaction	1
bisphenol A diglycidyl ether	decreases reaction, increases metabolic processing	1
tetrabromobisphenol A	decreases reaction, increases metabolic processing	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.