CLNK

Summary

CLNK (cytokine dependent hematopoietic cell linker, HGNC:17438) is a protein-coding gene on chromosome 4p16.1, encoding Cytokine-dependent hematopoietic cell linker (Q7Z7G1). An adapter protein which plays a role in the regulation of immunoreceptor signaling, including PLC-gamma-mediated B-cell antigen receptor (BCR) signaling and FC-epsilon R1-mediated mast cell degranulation.

MIST is a member of the SLP76 family of adaptors (see LCP2, MIM 601603; BLNK, MIM 604515). MIST plays a role in the regulation of immunoreceptor signaling, including PLC-gamma (PLCG1; MIM 172420)-mediated B cell antigen receptor (BCR) signaling and FC-epsilon R1 (see FCER1A, MIM 147140)-mediated mast cell degranulation (Cao et al., 1999 [PubMed 10562326]; Goitsuka et al., 2000, 2001 [PubMed 10744659] [PubMed 11463797]).

Source: NCBI Gene 116449 — RefSeq curated summary.

At a glance

• GWAS associations: 18
• Clinical variants (ClinVar): 119 total — 1 pathogenic
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_052964

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17438
Approved symbol	CLNK
Name	cytokine dependent hematopoietic cell linker
Location	4p16.1
Locus type	gene with protein product
Status	Approved
Aliases	MIST
Ensembl gene	ENSG00000109684
Ensembl biotype	protein_coding
OMIM	611434
Entrez	116449

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000226951, ENST00000507719, ENST00000515667

RefSeq mRNA: 1 — MANE Select: NM_052964 NM_052964

CCDS: CCDS47024

Canonical transcript exons

ENST00000226951 — 19 exons

Exon	Start	End
ENSE00000704070	10501256	10501411
ENSE00000704071	10507959	10508036
ENSE00000704148	10564671	10564777
ENSE00000704197	10566009	10566150
ENSE00000816703	10525841	10525922
ENSE00000816705	10540494	10540604
ENSE00000816706	10558407	10558452
ENSE00001020168	10542255	10542280
ENSE00001020171	10520791	10520831
ENSE00001020174	10532256	10532283
ENSE00001020179	10542022	10542041
ENSE00001617618	10528076	10528094
ENSE00002065755	10486395	10490613
ENSE00002071072	10684668	10684768
ENSE00003504349	10571741	10571778
ENSE00003562456	10513464	10513597
ENSE00003590375	10584927	10584955
ENSE00003629161	10667859	10667911
ENSE00003675736	10597978	10598049

Expression profiles

Bgee: expression breadth ubiquitous, 106 present calls, max score 81.46.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1717 / max 25.0367, expressed in 61 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
51376	0.1037	43
51377	0.0508	37
51375	0.0172	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	81.46	gold quality
buccal mucosa cell	CL:0002336	79.45	gold quality
adult mammalian kidney	UBERON:0000082	74.26	gold quality
metanephros cortex	UBERON:0010533	73.57	gold quality
gingival epithelium	UBERON:0001949	72.06	gold quality
kidney	UBERON:0002113	71.90	gold quality
body of tongue	UBERON:0011876	71.84	gold quality
cardia of stomach	UBERON:0001162	71.75	gold quality
tongue	UBERON:0001723	70.89	gold quality
cortex of kidney	UBERON:0001225	70.60	gold quality
subthalamic nucleus	UBERON:0001906	69.84	gold quality
lateral globus pallidus	UBERON:0002476	69.80	gold quality
superior surface of tongue	UBERON:0007371	69.71	gold quality
dorsal plus ventral thalamus	UBERON:0001897	69.58	gold quality
substantia nigra pars reticulata	UBERON:0001966	69.47	gold quality
vena cava	UBERON:0004087	69.32	gold quality
lymph node	UBERON:0000029	69.22	gold quality
saphenous vein	UBERON:0007318	69.22	gold quality
nipple	UBERON:0002030	69.12	gold quality
pericardium	UBERON:0002407	68.85	gold quality
pharyngeal mucosa	UBERON:0000355	68.78	gold quality
substantia nigra pars compacta	UBERON:0001965	68.76	gold quality
trachea	UBERON:0003126	68.66	gold quality
pons	UBERON:0000988	68.52	gold quality
lateral nuclear group of thalamus	UBERON:0002736	68.52	gold quality
renal medulla	UBERON:0000362	68.45	silver quality
esophagus squamous epithelium	UBERON:0006920	68.37	gold quality
pylorus	UBERON:0001166	68.24	gold quality
thymus	UBERON:0002370	68.16	silver quality
dorsal root ganglion	UBERON:0000044	67.97	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-GEOD-131882	yes	4521.97
E-CURD-119	yes	3844.30
E-CURD-135	yes	2512.60
E-MTAB-6075	yes	30.50
E-MTAB-6701	yes	16.55
E-CURD-114	yes	12.02
E-MTAB-6678	yes	9.25
E-ANND-3	yes	6.89
E-MTAB-7381	no	291.76

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): STAT5A

miRNA regulators (miRDB)

19 targeting CLNK, 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-570-3P	99.96	72.41	4910
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-4666B	99.64	68.69	1282
HSA-MIR-6126	99.62	68.09	996
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-4646-3P	98.65	66.98	693
HSA-MIR-4780	98.57	64.75	611
HSA-MIR-4435	95.90	65.47	1201
HSA-MIR-6777-3P	95.35	64.30	699

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 2)

• CLNK and ZNF518B SNPs may have potential as diagnostic and prognostic marker for Chinese gout patients. (PMID:25591661)
• Identify positive correlations between WDR1 and CLNK gene polymorphisms in Chinese-Tibetan gout populations. (PMID:26438387)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Clnk	ENSMUSG00000039315
rattus_norvegicus	Clnk	ENSRNOG00000051169

Paralogs (3): LCP2 (ENSG00000043462), BLNK (ENSG00000095585), SH2D6 (ENSG00000152292)

Protein

Protein identifiers

Cytokine-dependent hematopoietic cell linker — Q7Z7G1 (reviewed: Q7Z7G1)

Alternative names: Mast cell immunoreceptor signal transducer

All UniProt accessions (2): Q7Z7G1, D6RJB9

UniProt curated annotations — full annotation on UniProt →

Function. An adapter protein which plays a role in the regulation of immunoreceptor signaling, including PLC-gamma-mediated B-cell antigen receptor (BCR) signaling and FC-epsilon R1-mediated mast cell degranulation. Together with FGR, it acts as a negative regulator of natural killer cell-activating receptors and inhibits interferon-gamma production. Acts as a positive regulator of both T-cell receptor and natural killer T (NKT) cell receptor signaling in CD4-positive NKT cells. Together with MAP4K1, it enhances CD3-triggered activation of T-cells and subsequent IL2 production. May be involved in tumor necrosis factor induced cell death by promoting reactive oxidative species generation, and MLKL oligomerization, ultimately leading to necrosis. Involved in phosphorylation of LAT. May be involved in high affinity immunoglobulin epsilon receptor signaling in mast cells.

Subunit / interactions. When phosphorylated, interacts with PLCG1, PLCG2, GRB2, VAV and LAT. Interacts with LBR and AGO2. Interacts with FGR. Part of a complex consisting of CLNK, SKAP1 and FYB1. Interacts (via SH2 domain) with FYB1; this interaction allows SKAP1 and FYB1 to promote tyrosine phosphorylation of CLNK by LYN. Interacts (via SH2 domain) with MAP4K1.

Subcellular location. Cytoplasm.

Post-translational modifications. Tyrosine-phosphorylated upon BCR cross-linking. Tyrosine phosphorylation at both Tyr-69 and Tyr-96 are required for BCR-induced calcium response and are essential to restore PLCG2-mediated signaling in BLNK-deficient DT40 cells, but this phosphorylation is dispensable in cells expressing LAT. Interacts with the SH2 domain of PLCG1 via phosphorylated Tyr-96. Tyrosine phosphorylation is increased when complexed with SKAP1 and FYB1.

Domain organisation. The N-terminal proline-rich region interacts with the SH3 domain of PLCG1. The SH2 domain is important for restoration of BCR-induced calcium response and JNK2 activation in BLNK-deficient DT40 cells expressing LAT.

Isoforms (3)

UniProt ID	Names	Canonical?
Q7Z7G1-1	1	yes
Q7Z7G1-2	2
Q7Z7G1-3	3

RefSeq proteins (1): NP_443196* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000980	SH2	Domain
IPR036860	SH2_dom_sf	Homologous_superfamily
IPR051751	Immunoreceptor_sig_adapters	Family

Pfam: PF00017

UniProt features (18 total): region of interest 5, splice variant 4, modified residue 2, sequence conflict 2, chain 1, domain 1, sequence variant 1, compositionally biased region 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z7G1-F1	56.93	0.17

Functional residue map

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

Catalytic / active sites (1): 335 (interaction with fyb1)

Post-translational modifications (2): 96, 69

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 163 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION_INVOLVED_IN_IMMUNE_RESPONSE, GOZGIT_ESR1_TARGETS_DN, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, GOBP_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_MAST_CELL_ACTIVATION, GOBP_EXOCYTOSIS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_LYMPHOCYTE_MEDIATED_IMMUNITY, GOBP_REGULATION_OF_NATURAL_KILLER_CELL_ACTIVATION

GO Biological Process (5): positive regulation of natural killer cell cytokine production (GO:0002729), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), negative regulation of natural killer cell activation (GO:0032815), intracellular signal transduction (GO:0035556), mast cell degranulation (GO:0043303)

GO Molecular Function (2): protein-containing complex binding (GO:0044877), protein binding (GO:0005515)

GO Cellular Component (3): cytoplasm (GO:0005737), protein-containing complex (GO:0032991), mast cell granule (GO:0042629)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular anatomical structure	2
binding	2
natural killer cell cytokine production	1
positive regulation of natural killer cell mediated immunity	1
positive regulation of cytokine production involved in immune response	1
regulation of natural killer cell cytokine production	1
enzyme-linked receptor protein signaling pathway	1
natural killer cell activation	1
regulation of natural killer cell activation	1
negative regulation of lymphocyte activation	1
signal transduction	1
mast cell activation involved in immune response	1
mast cell mediated immunity	1
lysosome localization	1
leukocyte degranulation	1
establishment of organelle localization	1
cellular anatomical structure	1
cellular_component	1
lysosome	1

Protein interactions and networks

STRING

670 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLNK	LAT	O43561	788
CLNK	LYN	P07948	548
CLNK	PECAM1	P16284	544
CLNK	SNX22	Q96L94	523
CLNK	PPM1N	Q8N819	506
CLNK	GCSAM	Q8N6F7	500
CLNK	TMEM14A	Q9Y6G1	493
CLNK	PLCG1	P19174	486
CLNK	GGT5	P36269	430
CLNK	NFATC2	Q13469	427
CLNK	FGD6	Q6ZV73	424
CLNK	ZNF518B	Q9C0D4	419
CLNK	IL3	P08700	415
CLNK	MCHR2	Q969V1	414
CLNK	ARHGAP27	Q6ZUM4	413

IntAct

44 interactions, top by confidence:

A	B	Type	Score
PTK7	CLNK	psi-mi:“MI:0915”(physical association)	0.490
CLNK	SFMBT1	psi-mi:“MI:0915”(physical association)	0.490
PIK3R3	CLNK	psi-mi:“MI:0915”(physical association)	0.490
CLNK	GLIS3	psi-mi:“MI:0915”(physical association)	0.490
FAM217A	CLNK	psi-mi:“MI:0915”(physical association)	0.490
RPAIN	CLNK	psi-mi:“MI:0915”(physical association)	0.490
PPP1R7	CLNK	psi-mi:“MI:0915”(physical association)	0.490
CLNK	PIK3R1	psi-mi:“MI:0915”(physical association)	0.490
COQ9	CLNK	psi-mi:“MI:0915”(physical association)	0.490
CYB561D2	CLNK	psi-mi:“MI:0915”(physical association)	0.490
SOCS6	CLNK	psi-mi:“MI:0915”(physical association)	0.490
CLNK	NME4	psi-mi:“MI:0915”(physical association)	0.490
CLNK		psi-mi:“MI:0915”(physical association)	0.490
SFMBT1	CLNK	psi-mi:“MI:0915”(physical association)	0.490
CLNK	CYB561D2	psi-mi:“MI:0915”(physical association)	0.490
PIK3R1	CLNK	psi-mi:“MI:0915”(physical association)	0.490
CLNK	ERBB2	psi-mi:“MI:0407”(direct interaction)	0.440
CLNK	EGFR	psi-mi:“MI:0407”(direct interaction)	0.440
ERBB2	CLNK	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (30): FAM217A (Two-hybrid), GLIS3 (Two-hybrid), ARAP3 (Two-hybrid), COQ9 (Two-hybrid), CYB561D2 (Two-hybrid), NME4 (Two-hybrid), PIK3R1 (Two-hybrid), PIK3R3 (Two-hybrid), PPP1R7 (Two-hybrid), PTK7 (Two-hybrid), RPAIN (Two-hybrid), SFMBT1 (Two-hybrid), SOCS6 (Two-hybrid), ANKRD50 (Two-hybrid), BMX (Two-hybrid)

ESM2 similar proteins: A1X283, A2AAY5, A5D7F8, D3ZIE4, D3ZUI5, D4AB98, E2RP94, M0R4F8, O15117, O35601, O54824, O54967, O75128, O89032, Q04584, Q06649, Q07912, Q13094, Q13625, Q14005, Q15942, Q17R10, Q17R13, Q1LYG0, Q32LQ1, Q3TC93, Q3UMF0, Q498M5, Q4KM52, Q5DTU0, Q5JV73, Q5NBX1, Q5TCZ1, Q5U2X5, Q62523, Q7Z7G1, Q80TI1, Q8BI17, Q8BZI0, Q8CG79

Diamond homologs: G5ECJ6, O00459, O08908, O14508, O14544, O35716, O46404, O70512, O75791, O89100, P00523, P00524, P00525, P00526, P05480, P12931, P14084, P14085, P15054, P23726, P23727, P26450, P27870, P27986, P31693, P35991, P42685, P63185, Q06187, Q15464, Q2HJ53, Q45FX5, Q54RB7, Q5R685, Q5RCM6, Q62225, Q62662, Q63787, Q63788, Q63789

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 27 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
Constitutive Signaling by Aberrant PI3K in Cancer	5	39.6×	5e-06
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	5	30.2×	1e-05
PIP3 activates AKT signaling	5	20.9×	5e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	81
Likely benign	17
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
625783	GRCh37/hg19 4p16.1(chr4:9827438-10939900)	Pathogenic

SpliceAI

3225 predictions. Top by Δscore:

Variant	Effect	Δscore
4:10507953:CATTA:C	donor_loss	1.0000
4:10507954:ATTAC:A	donor_loss	1.0000
4:10507956:TA:T	donor_loss	1.0000
4:10507957:A:AG	donor_loss	1.0000
4:10508033:CATC:C	acceptor_gain	1.0000
4:10508034:ATC:A	acceptor_gain	1.0000
4:10508034:ATCCT:A	acceptor_loss	1.0000
4:10508035:TC:T	acceptor_gain	1.0000
4:10508036:CC:C	acceptor_gain	1.0000
4:10508037:C:CC	acceptor_gain	1.0000
4:10508037:CTGCA:C	acceptor_loss	1.0000
4:10508038:T:A	acceptor_loss	1.0000
4:10508046:A:T	acceptor_gain	1.0000
4:10564669:A:AC	donor_gain	1.0000
4:10564670:C:CC	donor_gain	1.0000
4:10564670:CT:C	donor_gain	1.0000
4:10564780:A:C	acceptor_gain	1.0000
4:10566149:TCCTA:T	acceptor_loss	1.0000
4:10571774:CTGGC:C	acceptor_gain	1.0000
4:10667857:A:AC	donor_gain	1.0000
4:10667857:ACTG:A	donor_gain	1.0000
4:10667857:ACTGC:A	donor_gain	1.0000
4:10667858:C:CC	donor_gain	1.0000
4:10667858:CTG:C	donor_gain	1.0000
4:10667858:CTGC:C	donor_gain	1.0000
4:10667858:CTGCC:C	donor_gain	1.0000
4:10667908:CAGC:C	acceptor_gain	1.0000
4:10501407:CCATC:C	acceptor_gain	0.9900
4:10501408:CATCC:C	acceptor_gain	0.9900
4:10507957:A:AC	donor_gain	0.9900

AlphaMissense

2858 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:10490608:A:C	F382L	0.996
4:10490608:A:T	F382L	0.996
4:10490610:A:G	F382L	0.996
4:10501392:C:G	R335P	0.995
4:10501395:A:T	V334D	0.995
4:10501353:A:G	L348S	0.994
4:10501400:G:C	F332L	0.994
4:10501400:G:T	F332L	0.994
4:10501402:A:G	F332L	0.994
4:10501311:C:G	R362P	0.993
4:10501314:A:G	I361T	0.991
4:10508018:A:G	W309R	0.991
4:10508018:A:T	W309R	0.991
4:10501286:A:C	F370L	0.990
4:10501286:A:T	F370L	0.990
4:10501288:A:G	F370L	0.990
4:10490604:A:G	S384P	0.985
4:10501356:A:T	V347D	0.984
4:10501314:A:C	I361R	0.983
4:10501314:A:T	I361K	0.983
4:10507997:G:T	R316S	0.982
4:10501401:A:G	F332S	0.981
4:10501312:G:T	R362S	0.980
4:10501327:A:C	Y357D	0.980
4:10501347:A:T	V350E	0.979
4:10490558:A:G	L399P	0.977
4:10501278:C:T	G373E	0.976
4:10508016:C:A	W309C	0.976
4:10508016:C:G	W309C	0.976
4:10501307:G:C	F363L	0.974

dbSNP variants (sampled 300 via entrez): RS1000002809 (4:10717433 T>C,G), RS10000059 (4:10720715 A>C), RS1000006086 (4:10640516 C>T), RS1000011417 (4:10728268 A>G), RS1000012414 (4:10704166 A>G), RS1000024502 (4:10668418 A>T), RS10000248 (4:10720872 A>G), RS1000029944 (4:10556689 T>C), RS1000042592 (4:10518506 A>C), RS1000042825 (4:10634263 A>C,G), RS1000043584 (4:10704441 T>C), RS1000047955 (4:10621346 T>C), RS1000052131 (4:10529710 C>G), RS1000113399 (4:10733749 G>A,T), RS1000122004 (4:10593052 T>C)

Disease associations

OMIM: gene MIM:611434 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): primary ovarian failure (MONDO:0005387)

Orphanet (1): NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST001509_10	Vitiligo	2.000000e-08
GCST002318_12	Rheumatoid arthritis	2.000000e-06
GCST002318_170	Rheumatoid arthritis	3.000000e-09
GCST004163_1	Resistance to antihypertensive treatment in hypertension	1.000000e-06
GCST004163_6	Resistance to antihypertensive treatment in hypertension	7.000000e-06
GCST005752_157	Systemic lupus erythematosus	3.000000e-06
GCST006575_30	Takayasu arteritis	8.000000e-06
GCST006618_5	Uterine fibroid size (maximum dimension)	9.000000e-07
GCST006959_171	Rheumatoid arthritis	7.000000e-09
GCST006959_84	Rheumatoid arthritis	2.000000e-06
GCST007320_69	Alzheimer’s disease or family history of Alzheimer’s disease	2.000000e-09
GCST007321_18	Family history of Alzheimer’s disease	1.000000e-08
GCST008972_107	Urate levels	3.000000e-60
GCST008972_162	Urate levels	9.000000e-09
GCST008972_195	Urate levels	4.000000e-101
GCST009391_606	Metabolite levels	8.000000e-06
GCST011096_23	Systemic lupus erythematosus	6.000000e-08
GCST012338_11	Gout	5.000000e-23

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:1002006	treatment-resistant hypertension
EFO:0009410	uterine fibroid measurement
EFO:0009268	family history of Alzheimer’s disease
EFO:0004531	urate measurement
EFO:0010505	isocitrate measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs13144136	Efficacy	3	Antihypertensives	Hypertension

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs13144136	CLNK	3	0.00	1	Antihypertensives

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol F	affects cotreatment, decreases methylation	1
bisphenol A	increases methylation	1
bisphenol S	decreases methylation	1
Fulvestrant	affects cotreatment, decreases methylation	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Methotrexate	decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00001951	PHASE2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	PHASE2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	PHASE2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	PHASE2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT02912104	PHASE1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	PHASE1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	PHASE1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	PHASE1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT00948857	PHASE2/PHASE3	TERMINATED	Dehydroepiandrosterone (DHEA) Treatment and Premature Ovarian Failure (POF)
NCT04031456	PHASE2/PHASE3	RECRUITING	Autologous PRP Infusion May Restore Ovarian Function and May Promote Folliculogenesis in POI Patients
NCT02043743	PHASE1/PHASE2	UNKNOWN	Autologous Stem Cells Transplantation in Patients With Idiopathic and Drug Induced Premature Ovarian Failure
NCT02062931	PHASE1/PHASE2	UNKNOWN	Autologous Mesenchymal Stem Cells Transplantation In Women With Premature Ovarian Failure
NCT02151890	PHASE1/PHASE2	COMPLETED	Pregnancy After Stem Cell Transplantation in Premature Ovarian Failure
NCT02372474	PHASE1/PHASE2	COMPLETED	It is a Real The First Baby Of Autologous Stem Cell Therapy in Premature Ovarian Failure
NCT02603744	PHASE1/PHASE2	UNKNOWN	Autologous Adipose Derived Mesenchymal Stromal Cells Transplantation in Women With Premature Ovarian Failure (POF)
NCT02644447	PHASE1/PHASE2	COMPLETED	Transplantation of HUC-MSCs With Injectable Collagen Scaffold for POF
NCT03069209	PHASE1/PHASE2	UNKNOWN	Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients With Premature Ovarian Failure (POF)
NCT03985462	PHASE1/PHASE2	WITHDRAWN	Very Small Embryonic-like Stem Cells for Ovary
NCT04009473	PHASE1/PHASE2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
NCT04071574	PHASE1/PHASE2	COMPLETED	Comparative Study on the Efficacy of Ovarian Stimulation Protocols on the Success Rate of ICSI in Female Infertility
NCT04922398	PHASE1/PHASE2	UNKNOWN	Ovarian Injection of PRP (Platelet -Rich Plasma) Vs Normal Saline in Premature Ovarian Insufficiency
NCT05462379	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Autologous Heterotopic Fresh Ovarian Graft in Woman With LACC Eligible for Pelvic Radiotherapy Treatment.
NCT06202547	PHASE1/PHASE2	UNKNOWN	Intra-ovarian Injection of MSC-EVs in Idiopathic Premature Ovarian Failure
NCT01129947	EARLY_PHASE1	WITHDRAWN	The Use of DHEA in Women With Premature Ovarian Failure
NCT05522634	EARLY_PHASE1	UNKNOWN	A Clinical Study of Chinese Herbal Compound TJAOA101 in the Treatment of Premature Ovarian Insufficiency
NCT07308327	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	The Influence of Gut Microbiota on Ovarian Function: A Single-center, Randomized,Double Blind, Parallel-controlled, Exploratory Clinical Trial
NCT00001275	Not specified	COMPLETED	Ovarian Follicle Function in Patients With Primary Ovarian Failure
NCT00001306	Not specified	COMPLETED	Steroid Therapy in Autoimmune Premature Ovarian Failure
NCT00006156	Not specified	COMPLETED	Feasibility Study for Development of an Early Test for Ovarian Failure
NCT00119925	Not specified	UNKNOWN	‘SPRING’-Study: Subfertility Guidelines: Patient Related Implementation in the Netherlands Among Gynaecologists