PYCR1

Summary

PYCR1 (pyrroline-5-carboxylate reductase 1, HGNC:9721) is a protein-coding gene on chromosome 17q25.3, encoding Pyrroline-5-carboxylate reductase 1, mitochondrial (P32322). Oxidoreductase that catalyzes the last step in proline biosynthesis, which corresponds to the reduction of pyrroline-5-carboxylate to L-proline using NAD(P)H.

This gene encodes an enzyme that catalyzes the NAD(P)H-dependent conversion of pyrroline-5-carboxylate to proline. This enzyme may also play a physiologic role in the generation of NADP(+) in some cell types. The protein forms a homopolymer and localizes to the mitochondrion. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 5831 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal recessive cutis laxa type 2B (Definitive, ClinGen) — +2 more curated relationships
• Clinical variants (ClinVar): 376 total — 20 pathogenic, 16 likely-pathogenic
• Phenotypes (HPO): 93
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_006907

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9721
Approved symbol	PYCR1
Name	pyrroline-5-carboxylate reductase 1
Location	17q25.3
Locus type	gene with protein product
Status	Approved
Aliases	P5C
Ensembl gene	ENSG00000183010
Ensembl biotype	protein_coding
OMIM	179035
Entrez	5831

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 18 protein_coding

ENST00000329875, ENST00000337943, ENST00000402252, ENST00000403172, ENST00000405481, ENST00000577624, ENST00000577756, ENST00000579366, ENST00000579698, ENST00000581271, ENST00000582198, ENST00000583564, ENST00000584848, ENST00000585215, ENST00000585244, ENST00000619204, ENST00000629768, ENST00000922965

RefSeq mRNA: 6 — MANE Select: NM_006907 NM_001282279, NM_001282280, NM_001282281, NM_001330523, NM_006907, NM_153824

CCDS: CCDS11794, CCDS11795, CCDS62365, CCDS62366, CCDS82221

Canonical transcript exons

ENST00000329875 — 7 exons

Exon	Start	End
ENSE00001295081	81934926	81935147
ENSE00002370677	81935337	81935516
ENSE00002385082	81934326	81934489
ENSE00002427493	81934653	81934745
ENSE00002726511	81936748	81937300
ENSE00003679626	81936123	81936193
ENSE00003890560	81932391	81933376

Expression profiles

Bgee: expression breadth ubiquitous, 224 present calls, max score 96.56.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.5591 / max 139.1647, expressed in 1570 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
168866	10.8506	1539
168865	6.2332	1354
168864	0.9921	639
168867	0.4832	269

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	96.56	gold quality
body of pancreas	UBERON:0001150	95.84	gold quality
parotid gland	UBERON:0001831	92.22	gold quality
ventricular zone	UBERON:0003053	91.39	gold quality
pancreas	UBERON:0001264	90.82	gold quality
mucosa of transverse colon	UBERON:0004991	90.69	gold quality
saliva-secreting gland	UBERON:0001044	89.49	gold quality
pancreatic ductal cell	CL:0002079	89.34	silver quality
embryo	UBERON:0000922	88.92	gold quality
ganglionic eminence	UBERON:0004023	88.66	gold quality
tibia	UBERON:0000979	88.34	gold quality
minor salivary gland	UBERON:0001830	88.33	gold quality
body of stomach	UBERON:0001161	88.05	gold quality
cartilage tissue	UBERON:0002418	87.84	gold quality
stomach	UBERON:0000945	86.96	gold quality
periodontal ligament	UBERON:0008266	86.70	gold quality
cortical plate	UBERON:0005343	86.40	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.16	gold quality
mouth mucosa	UBERON:0003729	86.12	gold quality
olfactory bulb	UBERON:0002264	86.08	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.92	gold quality
type B pancreatic cell	CL:0000169	84.20	gold quality
islet of Langerhans	UBERON:0000006	84.13	gold quality
pituitary gland	UBERON:0000007	83.79	gold quality
diaphragm	UBERON:0001103	83.74	gold quality
lower esophagus mucosa	UBERON:0035834	83.66	gold quality
adenohypophysis	UBERON:0002196	83.44	gold quality
smooth muscle tissue	UBERON:0001135	83.09	gold quality
esophagus mucosa	UBERON:0002469	82.69	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	82.61	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-13	yes	27.92
E-CURD-112	yes	14.97
E-ANND-3	yes	11.31
E-MTAB-8271	yes	8.34
E-MTAB-9689	no	280.95
E-MTAB-10290	no	135.67

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, TP53

miRNA regulators (miRDB)

24 targeting PYCR1, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-378A-5P	99.65	66.33	1311
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-1253	99.12	67.08	1688
HSA-MIR-4504	99.10	69.14	1328
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-5000-3P	98.79	65.63	1251
HSA-MIR-7113-3P	98.75	65.71	1120
HSA-MIR-323A-5P	98.59	65.13	651
HSA-MIR-4290	98.51	65.17	907
HSA-MIR-4436A	98.05	64.83	1140
HSA-MIR-4287	97.55	67.24	1247

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Mutagenesis and kinetic studies reveal the pivotal roles of the dinucleotide-binding Rossmann motif and residue Glu221 in the human enzyme Pyrroline-5-carboxylate reductase(P5CR). (PMID:16730026)
• In Autosomal-recessive cutis laxa type 2, a single nucleotide change leads to a missense mutation adjacent to a splice junction in the gene encoding PYCR1. (PMID:19576563)
• Mutations in PYCR1 cause cutis laxa with progeroid features. (PMID:19648921)
• The phenotype caused by PYCR1 mutations corresponds to geroderma osteodysplasticum rather than ARCL2B. (PMID:21204221)
• Mutation analysis revealed the presence of disease-causing variants in PYCR1, including a novel deletion of the entire PYCR1 gene in one family, and in each of the other patients the homozygous missense mutations. (PMID:21487760)
• A novel mutation in PYCR1 causes an autosomal recessive cutis laxa with premature aging features in a family. (PMID:21567914)
• The findings presented here suggest a mutation screening of PYCR1 and cardiovascular survey in patients with De Barsy syndrome (DBS). (PMID:22052856)
• Identification of two new mutations in the PYCR1 gene in patients with autosomal recessive cutis laxa, type 2. (PMID:23531708)
• Data suggest that DJ-1 and PYCR1 are on the same pathway of anti-oxidative stress protection of the cells. (PMID:23743200)
• our current study presents the second largest group of patients with PYCR1-related ARCL and expands the clinical and genetic spectrum. (PMID:24035636)
• confirming that indeed PYCR1 generates L-pipecolic acid from Delta(1)-piperideine-6-carboxylate (PMID:24431009)
• Silencing of both PYCR1 and PYCR2 completely abolished anti-oxidation activity of RRM2B, demonstrating a functional collaboration of these metabolic enzymes in response to oxidative stress. (PMID:26733354)
• Results indicate that single-nucleotide polymorphism (SNP)-derived mutations, R119G and G206W, enhance the rigidity of pyrroline-5-carboxylate reductase (P5CR) structure. (PMID:27677826)
• Authors found that PYCR1 was highly expressed in prostate cancer tissues and then knocked down PYCR1 in PCa cell lines (DU145, PC-3 and LNCap) via lentivirus-mediated gene delivery and analyzed its biological function. (PMID:28078560)
• experimental results indicate the R119G mutation could be an involving pathomechanism for Autosomal recessive cutis laxa . (PMID:28194412)
• PYCR1 forms a concentration-dependent decamer in solution, consistent with the pentamer-of-dimers assembly seen crystallographically (PMID:28258219)
• these findings revealed that the mRNA and protein PYCR1 levels were significantly related to the poor outcome in either ER-negative or ER-positive breast cancer. PYCR1 could serve as a prognostic biomarker, therapeutic target and predictive biomarker for breast cancers. (PMID:28379297)
• Authors describe a biosynthetic pathway exhibited by cells expressing mutant IDH1. By virtue of a change in cellular redox homeostasis, IDH1-mutated cells synthesize excess glutamine-derived proline through enhanced activity of pyrroline 5-carboxylate reductase 1 (PYCR1), coupled to NADH oxidation. (PMID:29562167)
• we firmly establish biallelic mutations in POLR3A as the genetic cause of a recognizable, neonatal, Wiedemann-Rautenstrauch-like progeroid syndrome. Thus, we suggest that POLR3A mutations are causal for a portion of under-diagnosed early-onset segmental progeroid syndromes (PMID:30450527)
• PYCR1 is negatively regulated by miR-488 and then promotes the occurrence and development of non-small-cell lung cancer and activates p38 MAPK pathway. (PMID:30605882)
• High PYCR1 expression is associated with migration and Invasion of Nonsmall Cell Lung Cancer. (PMID:30916574)
• acetylation of PYCR1 at K228 inhibits cell proliferation, while deacetylation of PYCR1 mediated by SIRT3 increases PYCR1’s activity. Our findings on the regulation of PYCR1 linked proline metabolism with SIRT3, CBP and cell growth, thus providing a potential approach for cancer therapy. (PMID:31108370)
• PYCR1 plays a role in the proliferation, epithelial-mesenchymal transition and drug resistance by regulating STAT3-mediated p38 MAPK and NF-kappaB signalling pathways in the colorectal cancer cells.PYCR1 is highly espressed in tissues and cells of the colorectal cancer patients. (PMID:31606203)
• PYCR1 interference inhibits cell growth and survival via c-Jun N-terminal kinase/insulin receptor substrate 1 (JNK/IRS1) pathway in hepatocellular cancer. (PMID:31619254)
• Mitochondrial oxidative stress by Lon-PYCR1 maintains an immunosuppressive tumor microenvironment that promotes cancer progression and metastasis. (PMID:31987921)
• High PYCR1 expression is associated with lung adenocarcinoma. (PMID:32133692)
• Oncogenic Kaposi’s sarcoma-associated herpesvirus (KSHV) K1 oncoprotein interacted with and activated PYCR enzyme, increasing intracellular proline concentration. Consequently, the K1-PYCR interaction promoted tumor cell growth in 3D spheroid culture and tumorigenesis in nude mice. This study demonstrates that an increase of proline biosynthesis induced by K1-PYCR interaction is critical for KSHV-mediated tumorigenesis. (PMID:32213586)
• Dysregulation of USP18/FTO/PYCR1 signaling network promotes bladder cancer development and progression. (PMID:33461172)
• PYCR1 promotes bladder cancer by affecting the Akt/Wnt/beta-catenin signaling. (PMID:33689096)
• MiR-328-3p inhibits lung adenocarcinoma-genesis by downregulation PYCR1. (PMID:33706104)
• Deciphering the effects of PYCR1 on cell function and its associated mechanism in hepatocellular carcinoma. (PMID:34239351)
• MiR-1207-5p targets PYCR1 to inhibit the progression of prostate cancer. (PMID:34461437)
• MicroRNA hsa-miR-150-5p inhibits nasopharyngeal carcinogenesis by suppressing PYCR1 (pyrroline-5-carboxylate reductase 1). (PMID:34696668)
• Proline synthesis through PYCR1 is required to support cancer cell proliferation and survival in oxygen-limiting conditions. (PMID:35108535)
• Cancer-associated fibroblasts require proline synthesis by PYCR1 for the deposition of pro-tumorigenic extracellular matrix. (PMID:35760868)
• The role of PYCR1 in inhibiting 5-fluorouracil-induced ferroptosis and apoptosis through SLC25A10 in colorectal cancer. (PMID:36104652)
• SENP3 affects the expression of PYCR1 to promote bladder cancer proliferation and EMT transformation by deSUMOylation of STAT3. (PMID:36227136)
• LINC01123 acts as an oncogenic driver in lung adenocarcinoma by regulating the miR-4766-5p/PYCR1 axis. (PMID:36994814)
• Effects of PYCR1 on prognosis and immunotherapy plus tyrosine kinase inhibition responsiveness in metastatic renal cell carcinoma patients. (PMID:37517099)
• IGF1R-phosphorylated PYCR1 facilitates ELK4 transcriptional activity and sustains tumor growth under hypoxia. (PMID:37777542)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	pycr1b	ENSDARG00000098639
danio_rerio	pycr1a	ENSDARG00000102254
mus_musculus	Pycr1	ENSMUSG00000025140
rattus_norvegicus	Pycr1	ENSRNOG00000036682
drosophila_melanogaster	P5cr-2	FBGN0038516
caenorhabditis_elegans		WBGENE00010924

Paralogs (3): PYCR3 (ENSG00000104524), PYCR2 (ENSG00000143811), NOXRED1 (ENSG00000165555)

Protein

Protein identifiers

Pyrroline-5-carboxylate reductase 1, mitochondrial — P32322 (reviewed: P32322)

All UniProt accessions (13): E2QRB3, P32322, J3KQ22, J3KSA9, J3KTA8, J3QKT3, J3QKT4, J3QL23, J3QL24, J3QL32, J3QLK9, J3QR88, J3QRZ0

UniProt curated annotations — full annotation on UniProt →

Function. Oxidoreductase that catalyzes the last step in proline biosynthesis, which corresponds to the reduction of pyrroline-5-carboxylate to L-proline using NAD(P)H. At physiologic concentrations, has higher specific activity in the presence of NADH. Involved in the cellular response to oxidative stress.

Subunit / interactions. Homodecamer; composed of 5 homodimers (PubMed:16730026, PubMed:28258219, Ref.19). Interacts with LTO1.

Subcellular location. Mitochondrion.

Disease relevance. Cutis laxa, autosomal recessive, 2B (ARCL2B) [MIM:612940] A disorder characterized by an excessive congenital skin wrinkling, a large fontanelle with delayed closure, a typical facial appearance with downslanting palpebral fissures, a general connective tissue weakness, and varying degrees of growth and developmental delay and neurological abnormalities. Patients do not manifest metabolic abnormalities. The disease is caused by variants affecting the gene represented in this entry. Cutis laxa, autosomal recessive, 3B (ARCL3B) [MIM:614438] A disorder characterized by an aged appearance with distinctive facial features, sparse hair, ophthalmologic abnormalities, intrauterine growth retardation, and cutis laxa. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Subject to competitive inhibition by the reaction product proline. Subject to competitive inhibition by stearoyl coenzyme A.

Pathway. Amino-acid biosynthesis; L-proline biosynthesis; L-proline from L-glutamate 5-semialdehyde: step 1/1.

Similarity. Belongs to the pyrroline-5-carboxylate reductase family.

Isoforms (3)

UniProt ID	Names	Canonical?
P32322-1	1	yes
P32322-2	2
P32322-3	3

RefSeq proteins (6): NP_001269208, NP_001269209, NP_001269210, NP_001317452, NP_008838, NP_722546 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000304	Pyrroline-COOH_reductase	Family
IPR008927	6-PGluconate_DH-like_C_sf	Homologous_superfamily
IPR028939	P5C_Rdtase_cat_N	Domain
IPR029036	P5CR_dimer	Domain
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily
IPR053790	P5CR-like_CS	Conserved_site

Pfam: PF03807, PF14748

Enzyme classification (BRENDA):

• EC 1.5.1.2 — pyrroline-5-carboxylate reductase (BRENDA: 43 organisms, 56 substrates, 140 inhibitors, 118 Km, 52 kcat entries)

Substrate kinetics (BRENDA)

11 substrates with measured Km, best-characterized 11. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
1-PYRROLINE-5-CARBOXYLATE	0.02–2.887	41
NADH	0.025–1.55	26
NADPH	0.006–0.719	24
DL-PYRROLINE-5-CARBOXYLATE	0.051–0.62	5
L-PROLINE	0.12–50	5
NADP+	0.093–3.06	5
NAD+	0.151–10.5	3
L-PYRROLINE-5-CARBOXYLATE	0.33	2
3,4-DEHYDRO-L-PROLINE	0.141	1
DELTA1-PYRROLINE-3-HYDROXY-5-CARBOXYLATE	4.4	1
PYRROLINE-5-CARBOXYLATE	—	0

Catalyzed reactions (Rhea), 2 shown:

• L-proline + NAD(+) = (S)-1-pyrroline-5-carboxylate + NADH + 2 H(+) (RHEA:14105)
• L-proline + NADP(+) = (S)-1-pyrroline-5-carboxylate + NADPH + 2 H(+) (RHEA:14109)

UniProt features (69 total): binding site 18, helix 17, sequence variant 11, strand 10, modified residue 3, splice variant 2, mutagenesis site 2, sequence conflict 2, initiator methionine 1, chain 1, region of interest 1, turn 1

Structure

Experimental structures (PDB)

47 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9P0R	X-RAY DIFFRACTION	1.49
9S04	X-RAY DIFFRACTION	1.57
9P0S	X-RAY DIFFRACTION	1.58
8TD7	X-RAY DIFFRACTION	1.61
8TD2	X-RAY DIFFRACTION	1.65
9S01	X-RAY DIFFRACTION	1.65
9S02	X-RAY DIFFRACTION	1.65
9P0U	X-RAY DIFFRACTION	1.66
8TD3	X-RAY DIFFRACTION	1.67
9RZZ	X-RAY DIFFRACTION	1.7
8TD8	X-RAY DIFFRACTION	1.71
8TCX	X-RAY DIFFRACTION	1.72
8TCV	X-RAY DIFFRACTION	1.74
9P0Q	X-RAY DIFFRACTION	1.74
6XP1	X-RAY DIFFRACTION	1.75
8TD9	X-RAY DIFFRACTION	1.75
9Q46	X-RAY DIFFRACTION	1.75
8TD4	X-RAY DIFFRACTION	1.76
9P0T	X-RAY DIFFRACTION	1.79
9Q45	X-RAY DIFFRACTION	1.79
8TDC	X-RAY DIFFRACTION	1.8
9P0V	X-RAY DIFFRACTION	1.8
8TD5	X-RAY DIFFRACTION	1.81
8VRE	X-RAY DIFFRACTION	1.83
5UAV	X-RAY DIFFRACTION	1.85
5UAW	X-RAY DIFFRACTION	1.85
5UAX	X-RAY DIFFRACTION	1.85
8DKG	X-RAY DIFFRACTION	1.85
8TD1	X-RAY DIFFRACTION	1.88
5UAU	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P32322-F1	89.98	0.84

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 (18): 56; 56; 69–72; 70; 71; 95–97; 97; 164; 230; 237; 238; 6–11 …

Post-translational modifications (3): 2, 278, 301

Mutagenesis-validated functional residues (2):

Position	Phenotype
221	reduced enzyme activity.
238	decreased pyrroline-5-carboxylate reductase activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8964539	Glutamate and glutamine metabolism

MSigDB gene sets: 371 (showing top): MODULE_93, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_GLUTAMINE_FAMILY_AMINO_ACID_BIOSYNTHETIC_PROCESS, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_DN, GOBP_AMINO_ACID_BIOSYNTHETIC_PROCESS, GOBP_GLUTAMINE_FAMILY_AMINO_ACID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, SCHUHMACHER_MYC_TARGETS_UP, MCBRYAN_PUBERTAL_BREAST_4_5WK_DN, GOBP_NEGATIVE_REGULATION_OF_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY

GO Biological Process (6): cellular response to oxidative stress (GO:0034599), regulation of mitochondrial membrane potential (GO:0051881), L-proline biosynthetic process (GO:0055129), negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway (GO:1903377), obsolete proline biosynthetic process (GO:0006561), amino acid biosynthetic process (GO:0008652)

GO Molecular Function (4): pyrroline-5-carboxylate reductase activity (GO:0004735), identical protein binding (GO:0042802), protein binding (GO:0005515), oxidoreductase activity (GO:0016491)

GO Cellular Component (2): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of amino acids and derivatives	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to oxidative stress	1
cellular response to chemical stress	1
regulation of membrane potential	1
L-proline metabolic process	1
glutamate family amino acid biosynthetic process	1
neuron intrinsic apoptotic signaling pathway in response to oxidative stress	1
negative regulation of neuron apoptotic process	1
negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway	1
regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway	1
amino acid metabolic process	1
biosynthetic process	1
oxidoreductase activity, acting on the CH-NH group of donors, NAD or NADP as acceptor	1
protein binding	1
binding	1
catalytic activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

1820 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PYCR1	ALDH18A1	P54886	956
PYCR1	JAG2	Q9Y219	949
PYCR1	PCF11	O94913	918
PYCR1	GORAB	Q5T7V8	823
PYCR1	ATP6V0A2	Q9Y487	808
PYCR1	EFEMP2	O95967	779
PYCR1	ALDH4A1	P30038	768
PYCR1	PRODH	O43272	762
PYCR1	LTO1	Q8WV07	757
PYCR1	POLR2A	P24928	753
PYCR1	PRODH	O43272	734
PYCR1	OAT	P04181	712
PYCR1	FBLN5	Q9UBX5	693
PYCR1	TRIM11	Q96F44	667
PYCR1	PLEKHF1	Q96S99	666

IntAct

146 interactions, top by confidence:

A	B	Type	Score
CDC23	BUB1B	psi-mi:“MI:0914”(association)	0.790
ANAPC16	BUB1B	psi-mi:“MI:0914”(association)	0.730
ANAPC2	BUB1B	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
PYCR1	PYCR1	psi-mi:“MI:0407”(direct interaction)	0.680
PYCR1	PYCR1	psi-mi:“MI:0915”(physical association)	0.680
rep	POLA1	psi-mi:“MI:0914”(association)	0.670
PARK7	PYCR1	psi-mi:“MI:0915”(physical association)	0.610
PYCR1	PARK7	psi-mi:“MI:0403”(colocalization)	0.610
PYCR1	PARK7	psi-mi:“MI:0915”(physical association)	0.610
TNPO2	PYCR1	psi-mi:“MI:0915”(physical association)	0.560
HNRNPH2	PLOD2	psi-mi:“MI:0914”(association)	0.530
PYCR1	PYCR3	psi-mi:“MI:0914”(association)	0.530
rep	PYCR1	psi-mi:“MI:0914”(association)	0.460
AIFM1	HAX1	psi-mi:“MI:2364”(proximity)	0.420
AIFM1	SEC16A	psi-mi:“MI:2364”(proximity)	0.420
HTRA2	HAX1	psi-mi:“MI:2364”(proximity)	0.420

BioGRID (273): PYCR1 (Affinity Capture-MS), PYCR1 (Affinity Capture-MS), PYCR1 (Affinity Capture-MS), PYCR1 (Affinity Capture-MS), NUDT5 (Affinity Capture-MS), PYCR2 (Affinity Capture-MS), KLHDC10 (Affinity Capture-MS), PYCRL (Affinity Capture-MS), CCDC47 (Co-fractionation), PYCR1 (Co-fractionation), PYCR1 (Affinity Capture-MS), PYCR1 (Affinity Capture-MS), PYCR1 (Affinity Capture-MS), PYCR1 (Proximity Label-MS), PYCR1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0C1E1C6, A0A348AXY1, A0A411KUQ8, A1CP85, B6HAA7, B8M0U4, C5PA86, L0E163, P00927, P0CM22, P0CM23, P32263, P32322, P40386, P41835, P54889, Q00055, Q09921, Q17QJ7, Q20848, Q39659, Q4P219, Q4PNS1, Q4R6W7, Q4WEE0, Q55E34, Q58DT4, Q59W33, Q5R9X6, Q5RAQ3, Q5SPD7, Q5ZKA5, Q6AY23, Q6CR99, Q6FN96, Q6J5J3, Q6ZZF4, Q759G5, Q7ZA43, Q8K009

Diamond homologs: A0A411KUQ8, P32322, Q12641, Q12740, Q17QJ7, Q4R6W7, Q58D08, Q58DT4, Q5R9X6, Q6AY23, Q922Q4, Q922W5, A0A348AXY1, A1L2Q8, E0TY11, O04016, P0A9L8, P0A9L9, P0C1E4, P0C1E5, P0CI77, P17817, P22008, P27771, P32263, P46725, P52053, P54552, P54893, P54904, P74572, P9WHU6, P9WHU7, Q04708, Q20848, Q4R531, Q53H96, Q5PQJ6, Q5RAQ3, Q5SPD7

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 153 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Inhibition of the proteolytic activity of APC/C required for the onset of anaphase by mitotic spindle checkpoint components	7	42.3×	8e-08
Inactivation of APC/C via direct inhibition of the APC/C complex	7	34.6×	1e-07
Phosphorylation of the APC/C	6	31.1×	2e-06
Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase	6	29.7×	2e-06
Aberrant regulation of mitotic exit in cancer due to RB1 defects	6	29.7×	2e-06
APC-Cdc20 mediated degradation of Nek2A	7	28.2×	3e-07
APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint	7	28.2×	3e-07
Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins	7	27.2×	4e-07

GO biological processes:

GO term	Partners	Fold	FDR
protein branched polyubiquitination	6	38.9×	3e-06
anaphase-promoting complex-dependent catabolic process	7	37.8×	4e-07
regulation of meiotic cell cycle	6	35.4×	4e-06
protein K11-linked ubiquitination	6	18.1×	2e-04
regulation of mitotic cell cycle	6	11.1×	2e-03
protein K48-linked ubiquitination	7	9.1×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	20
Likely pathogenic	16
Uncertain significance	133
Likely benign	150
Benign	16

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
13190	NM_006907.4(PYCR1):c.797G>A (p.Arg266Gln)	Pathogenic
13191	NM_006907.4(PYCR1):c.616G>T (p.Gly206Trp)	Pathogenic
13192	NM_006907.4(PYCR1):c.618_633+7del	Pathogenic
13195	NM_006907.4(PYCR1):c.11del (p.Gly4fs)	Pathogenic
13196	NM_006907.4(PYCR1):c.355C>G (p.Arg119Gly)	Pathogenic
2082773	NM_006907.4(PYCR1):c.570_571insA (p.Gly191fs)	Pathogenic
2840833	NM_006907.4(PYCR1):c.486_517del (p.Glu163fs)	Pathogenic
29864	NM_006907.4(PYCR1):c.345del (p.Arg116fs)	Pathogenic
3069061	NM_006907.4(PYCR1):c.148del (p.Gly49_Val50insTer)	Pathogenic
3662010	NM_006907.4(PYCR1):c.138+2T>G	Pathogenic
3711852	NM_006907.4(PYCR1):c.633+2T>G	Pathogenic
4720032	NM_006907.4(PYCR1):c.118del (p.Ala40fs)	Pathogenic
4724740	NM_006907.4(PYCR1):c.509_513del (p.Val170fs)	Pathogenic
4725770	NM_006907.4(PYCR1):c.176_194del (p.Thr59fs)	Pathogenic
4764024	NM_006907.4(PYCR1):c.663_670dup (p.Pro224fs)	Pathogenic
488457	NM_006907.4(PYCR1):c.59dup (p.Ala21fs)	Pathogenic
694681	NM_006907.4(PYCR1):c.11G>T (p.Gly4Val)	Pathogenic
694712	NM_006907.4(PYCR1):c.540+1G>A	Pathogenic
871527	NM_006907.4(PYCR1):c.349G>T (p.Val117Phe)	Pathogenic
996064	NM_006907.4(PYCR1):c.67+2T>A	Pathogenic
1526132	NM_006907.4(PYCR1):c.540+1G>T	Likely pathogenic
1526245	NM_006907.4(PYCR1):c.556G>T (p.Asp186Tyr)	Likely pathogenic
2572601	NM_006907.4(PYCR1):c.386_387insCGCA (p.Glu130fs)	Likely pathogenic
2882123	NM_006907.4(PYCR1):c.291_294dup (p.Val99fs)	Likely pathogenic
3583145	NM_006907.4(PYCR1):c.394_400del (p.Ala132fs)	Likely pathogenic
3583146	NM_006907.4(PYCR1):c.318+1G>A	Likely pathogenic
3583147	NM_006907.4(PYCR1):c.231dup (p.Ile78fs)	Likely pathogenic
392367	NM_006907.4(PYCR1):c.798-1G>A	Likely pathogenic
4076962	NM_006907.4(PYCR1):c.181C>T (p.Gln61Ter)	Likely pathogenic
426550	NM_006907.4(PYCR1):c.637G>A (p.Ala213Thr)	Likely pathogenic

SpliceAI

1055 predictions. Top by Δscore:

Variant	Effect	Δscore
17:81933372:GCTCC:G	acceptor_gain	1.0000
17:81933373:CTCC:C	acceptor_gain	1.0000
17:81933373:CTCCC:C	acceptor_gain	1.0000
17:81933374:TCC:T	acceptor_gain	1.0000
17:81933374:TCCCT:T	acceptor_gain	1.0000
17:81933375:CC:C	acceptor_gain	1.0000
17:81933375:CCC:C	acceptor_gain	1.0000
17:81933376:CC:C	acceptor_gain	1.0000
17:81933377:C:CC	acceptor_gain	1.0000
17:81934386:T:A	donor_gain	1.0000
17:81934486:CCCC:C	acceptor_gain	1.0000
17:81934487:CCC:C	acceptor_gain	1.0000
17:81934487:CCCC:C	acceptor_gain	1.0000
17:81934488:CC:C	acceptor_gain	1.0000
17:81934488:CCC:C	acceptor_gain	1.0000
17:81934489:CC:C	acceptor_gain	1.0000
17:81934490:C:A	acceptor_loss	1.0000
17:81934491:T:C	acceptor_loss	1.0000
17:81934647:A:AC	donor_gain	1.0000
17:81934648:C:CC	donor_gain	1.0000
17:81934924:A:AC	donor_gain	1.0000
17:81934925:C:CA	donor_gain	1.0000
17:81934978:TCC:T	donor_gain	1.0000
17:81934984:T:TA	donor_gain	1.0000
17:81935143:AGCTT:A	acceptor_gain	1.0000
17:81935145:CTT:C	acceptor_gain	1.0000
17:81935145:CTTC:C	acceptor_loss	1.0000
17:81935146:TT:T	acceptor_gain	1.0000
17:81935147:TC:T	acceptor_loss	1.0000
17:81935148:C:CC	acceptor_gain	1.0000

AlphaMissense

2066 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:81935097:G:C	N123K	0.999
17:81935097:G:T	N123K	0.999
17:81934354:C:G	A257P	0.998
17:81934711:C:T	G192D	0.998
17:81934332:C:G	R264P	0.997
17:81934715:C:A	G191W	0.997
17:81934944:A:C	S174R	0.997
17:81934944:A:T	S174R	0.997
17:81934946:T:G	S174R	0.997
17:81934951:C:T	G172E	0.997
17:81934952:C:A	G172W	0.997
17:81935075:C:A	G131W	0.997
17:81935362:C:T	G98D	0.997
17:81933371:A:G	L268P	0.996
17:81934723:A:G	L188P	0.996
17:81934727:C:G	A187P	0.996
17:81934936:C:T	G177D	0.996
17:81934942:C:T	G175D	0.996
17:81935060:C:G	A136P	0.996
17:81935075:C:G	G131R	0.996
17:81935075:C:T	G131R	0.996
17:81935108:A:G	C120R	0.996
17:81935365:G:T	A97D	0.996
17:81936162:G:C	S33R	0.996
17:81936162:G:T	S33R	0.996
17:81936164:T:G	S33R	0.996
17:81934353:G:T	A257D	0.995
17:81934439:C:A	K228N	0.995
17:81934439:C:G	K228N	0.995
17:81934482:G:T	A214D	0.995

dbSNP variants (sampled 300 via entrez): RS1000620594 (17:81938144 A>T), RS1000962824 (17:81933173 GAA>G), RS1001510551 (17:81934791 C>T), RS1002232798 (17:81931890 C>T), RS1002289761 (17:81937135 A>AG), RS1002941338 (17:81937433 C>A,G,T), RS1002965607 (17:81934747 T>A,C), RS1003065407 (17:81932668 G>A,C), RS1003276150 (17:81936199 G>A), RS1003548171 (17:81932326 T>C,G), RS1004602308 (17:81934394 A>G), RS1005408145 (17:81933941 G>A,C), RS1005428765 (17:81938902 C>T), RS1005693203 (17:81936468 G>A), RS1005701798 (17:81936768 G>A,C,T)

Disease associations

OMIM: gene MIM:179035 | disease phenotypes: MIM:612940, MIM:614438

GenCC curated gene-disease

Disease	Classification	Inheritance
PYCR1-related de Barsy syndrome	Definitive	Autosomal recessive
autosomal recessive cutis laxa type 2B	Definitive	Autosomal recessive
geroderma osteodysplastica	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
autosomal recessive cutis laxa type 2B	Definitive	AR

Mondo (5): autosomal recessive cutis laxa type 2B (MONDO:0013051), PYCR1-related de Barsy syndrome (MONDO:0013755), cutis laxa (MONDO:0016175), microcephaly (MONDO:0001149), geroderma osteodysplastica (MONDO:0009271)

Orphanet (4): Autosomal recessive cutis laxa type 2B (Orphanet:357064), Cutis laxa (Orphanet:209), PYCR1-related De Barsy syndrome (Orphanet:293633), De Barsy syndrome (Orphanet:2962)

HPO phenotypes

93 total (30 of 93 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000218	High palate
HP:0000233	Thin vermilion border
HP:0000238	Hydrocephalus
HP:0000239	Large fontanelles
HP:0000252	Microcephaly
HP:0000272	Malar flattening
HP:0000303	Mandibular prognathia
HP:0000316	Hypertelorism
HP:0000325	Triangular face
HP:0000337	Broad forehead
HP:0000343	Long philtrum
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000411	Protruding ear
HP:0000414	Bulbous nose
HP:0000418	Narrow nasal ridge
HP:0000430	Underdeveloped nasal alae
HP:0000460	Narrow nose
HP:0000478	Abnormality of the eye
HP:0000482	Microcornea
HP:0000490	Deeply set eye
HP:0000494	Downslanted palpebral fissures
HP:0000501	Glaucoma
HP:0000504	Abnormality of vision
HP:0000518	Cataract
HP:0000592	Blue sclerae
HP:0000601	Hypotelorism

GWAS associations

0 associations (top):

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D003483	Cutis Laxa	C16.320.850.180; C17.300.230; C17.800.827.180
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
C567855	Cutis Laxa, Autosomal Recessive, Type IIB (supp.)
C537799	Gerodermia osteodysplastica (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4296002 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 11,884 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL673	PARGYLINE	4	11,884

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

ChEMBL bioactivities

5 potent at pChembl≥5 of 41 total, top 5 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.30	Kd	50.33	nM	CHEMBL5653589
7.30	ED50	50.33	nM	CHEMBL5653589
5.06	IC50	8800	nM	CHEMBL4442920
5.04	IC50	9200	nM	CHEMBL4452615
5.01	IC50	9700	nM	CHEMBL4462797

PubChem BioAssay actives

4 with measured affinity, of 73 total; 4 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149158: Binding affinity to human PYCR1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0503	uM
N-[(4-bromophenyl)methyl]-N-methylprop-2-yn-1-amine	1589018: Inhibition of 6x-His-tagged and SUMO tagged human PYCR1 expressed in Escherichia coli BL21 (DE3) cells assessed as reduction in NADH oxidation incubated for 1 hr	ic50	8.8000	uM
N-[(2,4-dichlorophenyl)methyl]-N-methylprop-2-yn-1-amine	1589018: Inhibition of 6x-His-tagged and SUMO tagged human PYCR1 expressed in Escherichia coli BL21 (DE3) cells assessed as reduction in NADH oxidation incubated for 1 hr	ic50	9.2000	uM
N-[(4-iodophenyl)methyl]-N-methylprop-2-yn-1-amine	1589018: Inhibition of 6x-His-tagged and SUMO tagged human PYCR1 expressed in Escherichia coli BL21 (DE3) cells assessed as reduction in NADH oxidation incubated for 1 hr	ic50	9.7000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases methylation, affects cotreatment	4
Cadmium Chloride	decreases expression, increases abundance, increases expression	4
bisphenol A	decreases expression	2
Acetaminophen	decreases expression	2
Cadmium	increases abundance, increases expression	2
Estradiol	increases expression	2
Plant Extracts	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
chloroacetaldehyde	affects expression	1
benzo(b)fluoranthene	decreases expression, affects cotreatment	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases expression, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
benz(a)anthracene	affects cotreatment, decreases expression	1
chrysene	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
LDN 193189	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1

ChEMBL screening assays

12 unique, capped per target: 12 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4119009	Binding	Binding affinity to PYCR1 in human NCI-H358 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

6 cell lines: 6 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D1QA	Abcam K-562 PYCR1 KO	Cancer cell line	Female
CVCL_D2LW	Abcam Raji PYCR1 KO	Cancer cell line	Male
CVCL_TH84	HAP1 PYCR1 (-) 1	Cancer cell line	Male
CVCL_TH85	HAP1 PYCR1 (-) 2	Cancer cell line	Male
CVCL_TH86	HAP1 PYCR1 (-) 3	Cancer cell line	Male
CVCL_WQ44	Abcam Jurkat PYCR1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03887208	PHASE1/PHASE2	COMPLETED	Therapy of Scars and Cutis Laxa With Autologous Adipose Derived Mesenchymal Stem Cells
NCT01293864	Not specified	TERMINATED	Structural Analysis of Human Tissue
NCT01658163	Not specified	COMPLETED	Use of 2-octyl-cyanoacrylate Together With a Self-adhering Mesh
NCT06330324	Not specified	ENROLLING_BY_INVITATION	Reproductive Options in Inherited Skin Diseases
NCT06330350	Not specified	RECRUITING	Qualitative Study in Patients With Genodermatoses and Healthcare Professionals on Reproductive Counselling
NCT07614997	Not specified	NOT_YET_RECRUITING	Effectiveness and Safety of the Ulthera® System for Skin Laxity in the Lower Face, Submentum and Neck
NCT05518188	PHASE1/PHASE2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
NCT00001639	Not specified	COMPLETED	Evaluation of Patients With Unresolved Chromosome Abnormalities
NCT01151462	Not specified	WITHDRAWN	Postnatal HCMV Infection in Very Preterm Infants. Implications, Morbidity, Growth and Neurodevelopmental Outcomes.
NCT01565005	Not specified	COMPLETED	Microcephaly Genetic Deficiency in Neural Progenitors
NCT02510170	Not specified	COMPLETED	Fetal and Maternal Head Circumference During Pregnancy in Israeli Population
NCT02741882	Not specified	COMPLETED	Zika and Microcephaly: Case-control Study
NCT02943304	Not specified	COMPLETED	Neurodevelopment Outcome of Newborns Exposed to Zika Virus (ZIKV) in Utero
NCT03255369	Not specified	UNKNOWN	Vertical Exposure to Zika Virus and Its Consequences for Child Neurodevelopment (ZIKVIRUSIFF)
NCT03325946	Not specified	RECRUITING	The FBRI VTC Neuromotor Research Clinic
NCT03330600	Not specified	COMPLETED	Efficacy of Aquatic Physiotherapy in Children With Microcephaly by Zika Virus Congenital Syndrome
NCT03548779	Not specified	COMPLETED	North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2
NCT03651687	Not specified	COMPLETED	Guangzhou Surveillance and Clinical Study in Microcephaly (GSCSM)
NCT03922594	Not specified	TERMINATED	Surveillance of Zika-related Microcephaly in Sub-Saharan Africa and Asia
NCT04816175	Not specified	COMPLETED	Intensive Therapy for Children With Microcephaly, Hyperkinetic Movements, or Global Developmental Delay
NCT05322980	Not specified	COMPLETED	Summary of Infants Weighing 500 Grams or Less
NCT06019182	Not specified	RECRUITING	MEHMO Natural History and Biomarkers
NCT06566066	Not specified	RECRUITING	Register for Patients With Thyroid Hormone Resistance.