LIMS2

Summary

LIMS2 (LIM zinc finger domain containing 2, HGNC:16084) is a protein-coding gene on chromosome 2q14.3, encoding LIM and senescent cell antigen-like-containing domain protein 2 (Q7Z4I7). Adapter protein in a cytoplasmic complex linking beta-integrins to the actin cytoskeleton, bridges the complex to cell surface receptor tyrosine kinases and growth factor receptors.

This gene encodes a member of a small family of focal adhesion proteins which interacts with ILK (integrin-linked kinase), a protein which effects protein-protein interactions with the extraceullar matrix. The encoded protein has five LIM domains, each domain forming two zinc fingers, which permit interactions which regulate cell shape and migration. A pseudogene of this gene is located on chromosome 4. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 55679 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal recessive limb-girdle muscular dystrophy type 2W (Supportive, GenCC) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 405 total — 1 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 15
• MANE Select transcript: NM_001161403

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16084
Approved symbol	LIMS2
Name	LIM zinc finger domain containing 2
Location	2q14.3
Locus type	gene with protein product
Status	Approved
Aliases	PINCH2, PINCH-2
Ensembl gene	ENSG00000072163
Ensembl biotype	protein_coding
OMIM	607908
Entrez	55679

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 21 protein_coding, 4 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000324938, ENST00000355119, ENST00000409254, ENST00000409286, ENST00000409455, ENST00000409754, ENST00000409808, ENST00000410011, ENST00000410038, ENST00000413578, ENST00000426981, ENST00000466410, ENST00000469300, ENST00000476932, ENST00000484252, ENST00000494613, ENST00000545738, ENST00000582671, ENST00000855737, ENST00000855738, ENST00000855739, ENST00000855740, ENST00000855741, ENST00000855742, ENST00000855743, ENST00000855744, ENST00000957031, ENST00000957032

RefSeq mRNA: 5 — MANE Select: NM_001161403 NM_001136037, NM_001161403, NM_001161404, NM_001256542, NM_017980

CCDS: CCDS2147, CCDS54394, CCDS54395, CCDS54396, CCDS58725

Canonical transcript exons

ENST00000355119 — 10 exons

Exon	Start	End
ENSE00002719114	127675014	127675530
ENSE00003484279	127657403	127657562
ENSE00003500067	127654830	127654896
ENSE00003553055	127642923	127643072
ENSE00003554840	127640070	127640145
ENSE00003582895	127642049	127642199
ENSE00003632365	127640270	127640318
ENSE00003644091	127654424	127654544
ENSE00003661260	127640896	127640988
ENSE00003682721	127638426	127639428

Expression profiles

Bgee: expression breadth ubiquitous, 237 present calls, max score 99.38.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.0771 / max 365.7139, expressed in 1209 samples.

FANTOM5 promoters (27 alternative TSS)

Promoter ID	TPM avg	Samples expressed
30557	3.4114	711
30556	3.2697	773
30558	1.1608	436
30560	0.5849	241
30559	0.4770	240
30561	0.3602	193
30552	0.2015	114
30547	0.2009	65
30536	0.1719	51
30537	0.1629	88

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	99.38	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.28	gold quality
lower esophagus	UBERON:0013473	99.26	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.16	gold quality
body of uterus	UBERON:0009853	99.13	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.12	gold quality
right coronary artery	UBERON:0001625	99.07	gold quality
popliteal artery	UBERON:0002250	99.06	gold quality
tibial artery	UBERON:0007610	99.06	gold quality
ascending aorta	UBERON:0001496	99.01	gold quality
thoracic aorta	UBERON:0001515	99.00	gold quality
aorta	UBERON:0000947	98.97	gold quality
descending thoracic aorta	UBERON:0002345	98.94	gold quality
left coronary artery	UBERON:0001626	98.87	gold quality
right lung	UBERON:0002167	98.86	gold quality
tibial nerve	UBERON:0001323	98.80	gold quality
mucosa of stomach	UBERON:0001199	98.76	gold quality
left uterine tube	UBERON:0001303	98.75	gold quality
coronary artery	UBERON:0001621	98.65	gold quality
right atrium auricular region	UBERON:0006631	98.64	gold quality
heart left ventricle	UBERON:0002084	98.17	gold quality
cardiac atrium	UBERON:0002081	98.09	gold quality
cardiac ventricle	UBERON:0002082	97.81	gold quality
sural nerve	UBERON:0015488	97.71	gold quality
upper lobe of left lung	UBERON:0008952	97.48	gold quality
endocervix	UBERON:0000458	97.32	gold quality
heart	UBERON:0000948	96.93	gold quality
omental fat pad	UBERON:0010414	96.86	gold quality
peritoneum	UBERON:0002358	96.78	gold quality
upper lobe of lung	UBERON:0008948	96.52	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	25.83
E-GEOD-84465	yes	25.39
E-ANND-3	yes	23.13

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

37 targeting LIMS2, 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-5193	100.00	67.26	1744
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-3191-3P	99.45	63.94	356
HSA-MIR-128-1-5P	99.33	60.46	332
HSA-MIR-128-2-5P	99.33	60.83	311
HSA-MIR-4254	99.11	65.15	1315
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-4252	98.45	66.37	987
HSA-MIR-4289	98.26	66.90	810
HSA-MIR-3614-3P	97.81	67.15	582
HSA-MIR-4308	97.56	67.13	1385
HSA-MIR-6818-5P	97.50	67.10	1167
HSA-MIR-6748-3P	97.20	65.66	836
HSA-MIR-10398-5P	97.12	64.94	1051
HSA-MIR-1306-5P	97.11	64.04	755

Literature-anchored findings (GeneRIF, showing 7)

• These results identify a novel nuclear and focal adhesion protein that associates with ILK and reveals an important role of PINCH-2 in the regulation of the PINCH-1-ILK interaction, cell shape change, and migration. (PMID:12167643)
• LIMS2 may be useful as a molecular biomarker and a therapeutic target by increasing its expression and activity in gastric cancer (PMID:16959213)
• PINCH-2 mRNA is overexpressed in malignant mesothelioma (PMID:20500520)
• Results defined the functional role of copy number variations involving PINCH-2 in cancer progression based on the field cancerization effect; cell migration and invasion through autocrine and paracrine function as part of the field cancerization effect. (PMID:25346044)
• Data indicate compound heterozygous missense mutations that are predicted to be pathogenic in LIM and senescent cell antigen-like domains 2 protein (LIMS2). (PMID:25589244)
• Mammalian cells have two functional PINCH proteins, PINCH1 and PINCH2. PINCH not only binds to Nck2 and engages in the signaling of growth factor receptors, but also forms a ternary complex with ILK and parvin (IPP complex). (PMID:27590440)
• Fluid shear stress modulates endothelial inflammation by targeting LIMS2. (PMID:32752897)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lims2	ENSMUSG00000024395
rattus_norvegicus	Lims2	ENSRNOG00000016021
drosophila_melanogaster	stck	FBGN0020249
drosophila_melanogaster	Zasp67	FBGN0036044
caenorhabditis_elegans		WBGENE00004030
caenorhabditis_elegans		WBGENE00006826

Paralogs (3): LIMS1 (ENSG00000169756), LIMS4 (ENSG00000256671), LIMS3 (ENSG00000256977)

Protein

Protein identifiers

LIM and senescent cell antigen-like-containing domain protein 2 — Q7Z4I7 (reviewed: Q7Z4I7)

Alternative names: LIM-like protein 2, Particularly interesting new Cys-His protein 2

All UniProt accessions (3): Q7Z4I7, F8WEF3, H0Y592

UniProt curated annotations — full annotation on UniProt →

Function. Adapter protein in a cytoplasmic complex linking beta-integrins to the actin cytoskeleton, bridges the complex to cell surface receptor tyrosine kinases and growth factor receptors. Plays a role in modulating cell spreading and migration.

Subunit / interactions. Interacts with TGFB1I1. Interacts with integrin-linked protein kinase 1 (ILK) via the first LIM domain, and in competition with LIMS1. Part of the heterotrimeric IPP complex composed of integrin-linked kinase (ILK), LIMS1 or LIMS2, and PARVA.

Subcellular location. Nucleus. Cell junction. Focal adhesion. Cell membrane.

Disease relevance. Muscular dystrophy, autosomal recessive, with cardiomyopathy and triangular tongue (MDRCMTT) [MIM:616827] An autosomal recessive muscular dystrophy characterized by childhood-onset of muscle weakness progressing to a severe quadriparesis. Additionally, patients have biventricular cardiac dysfunction due to dilated cardiomyopathy, and macroglossia with a small tip resulting in a triangular tongue. The disease may be caused by variants affecting the gene represented in this entry.

Isoforms (5)

UniProt ID	Names	Canonical?
Q7Z4I7-1	1, LIM-like protein 2B	yes
Q7Z4I7-2	2, LIM-like protein 2A
Q7Z4I7-3	3, LIM-like protein 2C
Q7Z4I7-4	4
Q7Z4I7-5	5

RefSeq proteins (5): NP_001129509, NP_001154875, NP_001154876, NP_001243471, NP_060450 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001781	Znf_LIM	Domain
IPR017351	PINCH-1-4-like	Family
IPR047944	LIMS1/2-like_LIM1	Domain
IPR047946	PINCH-1/2-like	Family

Pfam: PF00412

UniProt features (27 total): domain 5, splice variant 4, strand 4, sequence variant 3, turn 3, modified residue 3, sequence conflict 2, helix 2, chain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3IXE	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z4I7-F1	87.16	0.52

Functional residue map

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

Post-translational modifications (3): 22, 327, 328

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-446353	Cell-extracellular matrix interactions
R-HSA-1500931	Cell-Cell communication
R-HSA-446728	Cell junction organization

MSigDB gene sets: 165 (showing top): GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, GOBP_REGULATION_OF_HEPATOCYTE_PROLIFERATION, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, GOBP_GLAND_MORPHOGENESIS, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, PEREZ_TP63_TARGETS, CHANDRAN_METASTASIS_DN, GOBP_NEURAL_PRECURSOR_CELL_PROLIFERATION, GOBP_CELL_CELL_ADHESION, CAIRO_HEPATOBLASTOMA_CLASSES_DN, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_ACTIN_FILAMENT_ORGANIZATION, GOBP_NEGATIVE_REGULATION_OF_NEURAL_PRECURSOR_CELL_PROLIFERATION

GO Biological Process (11): integrin-mediated signaling pathway (GO:0007229), negative regulation of apoptotic process (GO:0043066), cell-cell junction organization (GO:0045216), neural precursor cell proliferation (GO:0061351), cell-cell adhesion (GO:0098609), positive regulation of substrate adhesion-dependent cell spreading (GO:1900026), negative regulation of cholangiocyte proliferation (GO:1904055), cholangiocyte proliferation (GO:1990705), negative regulation of neural precursor cell proliferation (GO:2000178), negative regulation of hepatocyte proliferation (GO:2000346), positive regulation of integrin-mediated signaling pathway (GO:2001046)

GO Molecular Function (2): metal ion binding (GO:0046872), protein binding (GO:0005515)

GO Cellular Component (8): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), focal adhesion (GO:0005925), membrane (GO:0016020), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Cell junction organization	1
Cell-Cell communication	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
negative regulation of epithelial cell proliferation	2
cell surface receptor signaling pathway	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
cell junction organization	1
cell population proliferation	1
cell adhesion	1
positive regulation of cell-substrate adhesion	1
substrate adhesion-dependent cell spreading	1
regulation of substrate adhesion-dependent cell spreading	1
regulation of cholangiocyte proliferation	1
cholangiocyte proliferation	1
epithelial cell proliferation	1
negative regulation of cell population proliferation	1
neural precursor cell proliferation	1
regulation of neural precursor cell proliferation	1
hepatocyte proliferation	1
regulation of hepatocyte proliferation	1
integrin-mediated signaling pathway	1
positive regulation of signal transduction	1
regulation of integrin-mediated signaling pathway	1
cation binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1
anchoring junction	1
cell-substrate junction	1
cell junction	1

Protein interactions and networks

STRING

708 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LIMS2	ILK	P57043	949
LIMS2	PARVA	Q9NVD7	844
LIMS2	PARVG	Q9HBI0	750
LIMS2	PARVB	Q9HBI1	675
LIMS2	TERF1	P54274	668
LIMS2	RSU1	Q15404	608
LIMS2	VCL	P18206	544
LIMS2	BCAS1	O75363	544
LIMS2	SNX12	Q9UMY4	418
LIMS2	NCK2	O43639	410
LIMS2	RIPK4	P57078	380
LIMS2	LIM2	P55344	379
LIMS2	ELOVL2	Q9NXB9	364
LIMS2	TRIM54	Q9BYV2	357
LIMS2	FERMT2	Q96AC1	333

IntAct

10 interactions, top by confidence:

A	B	Type	Score
ILK	ILVBL	psi-mi:“MI:0914”(association)	0.530
LRRK2	LIMS2	psi-mi:“MI:0407”(direct interaction)	0.440
LIMS2	HRH1	psi-mi:“MI:0915”(physical association)	0.370
LIMS2	HOXA1	psi-mi:“MI:0915”(physical association)	0.370
HIPK3	LIMS2	psi-mi:“MI:0915”(physical association)	0.370
	LIMS2	psi-mi:“MI:0915”(physical association)	0.370
PARVA	CREB1	psi-mi:“MI:0914”(association)	0.350
RSU1	LIMS2	psi-mi:“MI:0914”(association)	0.350

BioGRID (25): LIMS2 (Two-hybrid), LIMS2 (Two-hybrid), LIMS2 (Two-hybrid), LIMS2 (Two-hybrid), LIMS2 (Two-hybrid), KRT40 (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-5 (Two-hybrid), KRTAP10-3 (Two-hybrid), NOTCH2NL (Two-hybrid), LIMS2 (Two-hybrid), LIMS2 (Two-hybrid), LIMS2 (Two-hybrid), LIMS2 (Two-hybrid), LIMS2 (Negative Genetic)

ESM2 similar proteins: A0A2R8RWN9, A5PKA5, O15294, O89050, P25791, P25801, P48059, P49136, P49139, P49336, P56558, P61201, P61202, P61203, P61968, P61969, P79101, P81436, Q08211, Q1LZ94, Q27HV0, Q28141, Q2KJ33, Q3SWZ8, Q3UHD6, Q5FVB2, Q5M8V8, Q5R874, Q5RB35, Q5SRY7, Q5ZIH0, Q6DJ06, Q7Z4I7, Q801P0, Q8AW92, Q8CGY8, Q8K4V4, Q8R3L8, Q90XH3, Q91854

Diamond homologs: A1ZA47, A2ALU4, A5H447, D4A702, E1BKA3, O00151, O14639, O43294, O60711, O70209, O70400, O75112, O94929, P20271, P48059, P49023, P49024, P50464, P52944, Q09476, Q0WSN2, Q13796, Q15942, Q1JQB5, Q2KJ33, Q2TCH4, Q2YDK0, Q3MHZ4, Q3SX26, Q3SX40, Q3SYZ8, Q3T0X8, Q3TJD7, Q55BI0, Q5F464, Q5R7I1, Q5RCF7, Q5TD97, Q5U2Z2, Q5XI07

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
LIMS2	“form complex”	“IPP complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	2
Uncertain significance	212
Likely benign	126
Benign	43

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
222902	NM_001161403.3(LIMS2):c.968T>C (p.Leu323Pro)	Pathogenic
2585055	NM_001161403.3(LIMS2):c.238+1G>T	Likely pathogenic
3065195	NM_001161403.3(LIMS2):c.430del (p.His144fs)	Likely pathogenic

SpliceAI

2517 predictions. Top by Δscore:

Variant	Effect	Δscore
2:127639424:TGTTC:T	acceptor_gain	1.0000
2:127639425:GTTC:G	acceptor_gain	1.0000
2:127639426:TTC:T	acceptor_gain	1.0000
2:127639427:TC:T	acceptor_gain	1.0000
2:127639428:CC:C	acceptor_gain	1.0000
2:127639429:C:CC	acceptor_gain	1.0000
2:127639430:T:G	acceptor_loss	1.0000
2:127640068:A:AC	donor_gain	1.0000
2:127640069:C:CC	donor_gain	1.0000
2:127640141:CACCA:C	acceptor_gain	1.0000
2:127640143:CCA:C	acceptor_gain	1.0000
2:127640144:CA:C	acceptor_gain	1.0000
2:127640144:CAC:C	acceptor_gain	1.0000
2:127640146:C:CC	acceptor_gain	1.0000
2:127640891:CTCA:C	donor_loss	1.0000
2:127640892:TCA:T	donor_loss	1.0000
2:127640893:CA:C	donor_loss	1.0000
2:127640894:A:AC	donor_gain	1.0000
2:127640895:C:CC	donor_gain	1.0000
2:127640895:CCTGG:C	donor_gain	1.0000
2:127640984:AAGTG:A	acceptor_gain	1.0000
2:127640985:AGTG:A	acceptor_gain	1.0000
2:127640986:GTG:G	acceptor_gain	1.0000
2:127640987:TG:T	acceptor_gain	1.0000
2:127640988:GC:G	acceptor_loss	1.0000
2:127640989:C:CC	acceptor_gain	1.0000
2:127640989:CTGC:C	acceptor_loss	1.0000
2:127642044:CTCA:C	donor_loss	1.0000
2:127642919:CTACC:C	donor_loss	1.0000
2:127642920:TA:T	donor_loss	1.0000

AlphaMissense

2279 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:127639385:A:G	C308R	1.000
2:127639392:A:C	C305W	1.000
2:127639393:C:G	C305S	1.000
2:127639393:C:T	C305Y	1.000
2:127639394:A:G	C305R	1.000
2:127639394:A:T	C305S	1.000
2:127639399:G:T	P303H	1.000
2:127640099:G:C	C283W	1.000
2:127640100:C:T	C283Y	1.000
2:127640101:A:G	C283R	1.000
2:127640119:A:G	C277R	1.000
2:127640122:A:G	W276R	1.000
2:127640122:A:T	W276R	1.000
2:127640301:G:C	C257W	1.000
2:127640302:C:G	C257S	1.000
2:127640302:C:T	C257Y	1.000
2:127640303:A:G	C257R	1.000
2:127640303:A:T	C257S	1.000
2:127640313:G:C	F253L	1.000
2:127640313:G:T	F253L	1.000
2:127640315:A:G	F253L	1.000
2:127640904:A:C	Y249D	1.000
2:127640914:G:C	C245W	1.000
2:127640915:C:A	C245F	1.000
2:127640915:C:G	C245S	1.000
2:127640915:C:T	C245Y	1.000
2:127640916:A:G	C245R	1.000
2:127640916:A:T	C245S	1.000
2:127640919:A:C	Y244D	1.000
2:127640921:G:T	A243D	1.000

dbSNP variants (sampled 300 via entrez): RS1000019658 (2:127664829 A>G), RS1000023950 (2:127652732 T>C), RS1000035540 (2:127647396 G>A,C), RS1000118169 (2:127652975 G>A), RS1000162209 (2:127660468 T>C), RS1000189411 (2:127676153 T>C), RS1000226030 (2:127672368 C>T), RS1000299709 (2:127672697 G>A), RS1000435329 (2:127644179 G>A), RS1000631614 (2:127656739 G>A,C), RS1000636411 (2:127646212 C>T), RS1000637232 (2:127641635 G>A,C), RS1000797086 (2:127678103 T>C), RS1000856810 (2:127647242 G>A), RS1000908874 (2:127683009 A>G)

Disease associations

OMIM: gene MIM:607908 | disease phenotypes: MIM:616827, MIM:255200

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal recessive limb-girdle muscular dystrophy type 2W	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
autosomal recessive limb-girdle muscular dystrophy	Disputed	AR

Mondo (4): autosomal recessive limb-girdle muscular dystrophy type 2W (MONDO:0014788), myopathy, centronuclear, 2 (MONDO:0009709), neutropenia (MONDO:0001475), lymphopenia (MONDO:0003783)

Orphanet (2): Autosomal recessive centronuclear myopathy (Orphanet:169186), OBSOLETE: LIMS2-related myopathy (Orphanet:466801)

HPO phenotypes

15 total (17 of 15 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000158	Macroglossia
HP:0001324	Muscle weakness
HP:0001644	Dilated cardiomyopathy
HP:0001762	Talipes equinovarus
HP:0002273	Tetraparesis
HP:0003202	Skeletal muscle atrophy
HP:0003236	Elevated circulating creatine kinase concentration
HP:0003560	Muscular dystrophy
HP:0003676	Progressive
HP:0006673	Reduced systolic function
HP:0008981	Calf muscle hypertrophy
HP:0009025	Increased connective tissue
HP:0011463	Childhood onset
HP:0030284	Triangular tongue
HP:0001875	Decreased total neutrophil count
HP:0001888	Decreased total lymphocyte count

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001915_4	Alzheimer’s disease (cognitive decline)	2.000000e-06
GCST002718_5	Type 2 diabetes	3.000000e-06

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008231	Lymphopenia	C15.378.243.750.605; C15.378.553.546.605; C20.673.627
D009503	Neutropenia	C15.378.243.750.184.564; C15.378.553.546.184.564
C562934	Myopathy, Centronuclear, Autosomal Recessive (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	decreases methylation, decreases expression	2
GSK-J4	increases expression	1
TL8-506	affects cotreatment, increases expression	1
propionaldehyde	increases expression	1
titanium dioxide	increases expression, decreases methylation	1
cobaltous chloride	decreases expression	1
butyraldehyde	increases expression	1
zinc chromate	decreases expression, increases abundance	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
pentanal	increases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Aldehydes	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases abundance, decreases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Dexamethasone	increases expression	1
Methapyrilene	increases methylation	1
Poly I-C	affects cotreatment, increases expression	1
Silicon Dioxide	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	decreases expression	1
Valproic Acid	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00030758	PHASE4	UNKNOWN	Filgrastim or Pegfilgrastim in Preventing Neutropenia in Women Receiving Chemotherapy Following Surgery for Breast Cancer
NCT00125723	PHASE4	COMPLETED	FIRST - Study of Pegfilgrastim Administered in the First and Subsequent Cycles of Myelosuppressive Chemotherapy
NCT00194857	PHASE4	TERMINATED	Treatment of Anemia and Neutropenia in HIV/HCV Coinfected Patients Treated With Pegylated Interferon and Ribavirin
NCT00257790	PHASE4	COMPLETED	The Tobramycin Study
NCT00277160	PHASE4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00686543	PHASE4	COMPLETED	Oral Posaconazole in High Risk Patients With Gastrointestinal Dysfunction (Study P05115)
NCT01086878	PHASE4	COMPLETED	Safety of Cotrimoxazole in HIV- and HAART-exposed Infants
NCT01114165	PHASE4	COMPLETED	Value of the LightCycler® SeptiFast Test MGRADE for the Pathogen Detection in Neutropenic Hematological Patients
NCT01135589	PHASE4	UNKNOWN	Micafungin Prevention Study for Fungal Disease in Child Receiving Allogenic Hematopoietic Stem Cell Transplantation
NCT01571518	PHASE4	UNKNOWN	Prevention of Neutropenia After Using G-CSF With TAC Chemotherapy
NCT02621905	PHASE4	COMPLETED	Steady-State Comparative Bioavailability Study in Prophylaxis Patients of Lozanoc® 50 mg With Sporanox® 100 mg
NCT02967341	PHASE4	UNKNOWN	Blood Draw Validation for Ciprofloxacin Pharmacokinetic Research in Pediatric Cancer Patients
NCT04009941	PHASE4	COMPLETED	Efficacy and Safety of 4.5mg PEG-rhG-CSF Per Cycle in Preventing Neutropenia After Intensive Chemotherapy for Breast Cancer
NCT04904614	PHASE4	COMPLETED	Letermovir Use in Heart Transplant Recipients
NCT05626530	PHASE4	RECRUITING	Letermovir for Secondary Prophylaxis in Solid Organ Transplant Recipients
NCT06145321	PHASE4	ACTIVE_NOT_RECRUITING	Continuous Versus Bolus Administration of G-CSF in Children With Cancer
NCT00001338	PHASE3	COMPLETED	A Prospective, Randomized, Phase III Trial of FLAC (5-Fluorouracil, Leucovorin, Adriamycin, Cytoxan) Chemotherapy With GM-CSF (Granulocyte-Macrophage Colony-Stimulating Factor) Versus PIXY 321 in Advanced Breast Cancer
NCT00001646	PHASE3	COMPLETED	Voriconazole vs. Amphotericin B in the Treatment of Invasive Aspergillosis
NCT00002658	PHASE3	UNKNOWN	Combination Chemotherapy, Biological Therapy, and Bone Marrow Transplantation in Treating Patients With Acute Myeloid Leukemia
NCT00002719	PHASE3	COMPLETED	Combination Chemotherapy With or Without G-CSF in Treating Older Patients With Acute Myeloid Leukemia
NCT00003739	PHASE3	COMPLETED	Antibiotic Therapy With or Without G-CSF in Treating Children With Neutropenia and Fever Caused by Chemotherapy
NCT00020865	PHASE3	UNKNOWN	Levofloxacin Compared With Cefepime in Treating Cancer Patients With Fever and Neutropenia
NCT00035594	PHASE3	COMPLETED	Pegfilgrastim as Support to Advanced Breast Cancer Patients Receiving Chemotherapy
NCT00044486	PHASE3	COMPLETED	Prophylaxis Trial of Posaconazole Versus Standard Azole Therapy for Neutropenic Patients (Study P01899)
NCT00107081	PHASE3	TERMINATED	Low-risk Fever and Neutropenia in Children With Cancer: Safety and Efficacy of Oral Antibiotics in an Outpatient Setting
NCT00445497	PHASE3	UNKNOWN	Early Hospital Discharge or Standard Inpatient Care in Cancer Patients Receiving Antibiotics for Febrile Neutropenia
NCT00529282	PHASE3	TERMINATED	A Study of Ceftobiprole in Patients With Fever and Neutropenia.
NCT00627393	PHASE3	COMPLETED	Safety and Effectiveness of Granulocyte Transfusions in Resolving Infection in People With Neutropenia (The RING Study)
NCT00770172	PHASE3	COMPLETED	G-CSF in Preventing Neutropenia in Patients With Solid Tumors Who Are Receiving Chemotherapy
NCT00784368	PHASE3	COMPLETED	A Pharmacokinetic Study of JK1211(Itraconazole [Itrizole]) Oral Solution in Participants With Deep Mycosis and Those With Febrile Neutropenia Suspected of Fungal Infection
NCT00806351	PHASE3	TERMINATED	An Evaluation Of The Effectiveness And Safety Of Anidulafungin Compared To Caspofungin For The Treatment Of Serious Fungal Infection Due To Candida In Patients With A Dysfunctional Immune System
NCT00911170	PHASE3	COMPLETED	PAVES: Pegfilgrastim Anti-vascular Endothelial Growth Factor (VEGF) Evaluation Study
NCT01307579	PHASE3	COMPLETED	Caspofungin Versus Fluconazole in Preventing Invasive Fungal Infections (IFI) in Patients Undergoing Chemotherapy for Acute Myeloid Leukemia
NCT01371656	PHASE3	COMPLETED	Levofloxacin in Preventing Infection in Young Patients With Acute Leukemia Receiving Chemotherapy or Undergoing Stem Cell Transplantation
NCT01560195	PHASE3	UNKNOWN	A Study of Pegylated rhG-CSF as Support to Advanced Non-Small-Cell Lung Cancer (NSCLC) Patients Receiving Chemotherapy Receiving Chemotherapy
NCT01611051	PHASE3	COMPLETED	A Study Comparing Pegylated rhG-CSF and rhG-CSF as Support to Breast Cancer Patients Receiving Chemotherapy
NCT02238873	PHASE3	UNKNOWN	Pegfilgrastim on Day +3 Compared to Day +1 After Salvage Chemotherapy for Patients With Refractory or Relapsed Aggressive Lymphoma
NCT02414581	PHASE3	COMPLETED	Mouthwash With Chlorhexidine 0.12%/Ethyl Alcohol 7% Compared to Ethyl Alcohol 7%
NCT02643420	PHASE3	COMPLETED	SPI-2012 vs Pegfilgrastim in the Management of Neutropenia in Participants With Breast Cancer With Docetaxel and Cyclophosphamide (ADVANCE)
NCT02872103	PHASE3	COMPLETED	Placebo-controlled Trial of F-627 in Women With Breast Cancer Receiving Myelotoxic Chemotherapy