LSM14A

Summary

LSM14A (LSM14A mRNA processing body assembly factor, HGNC:24489) is a protein-coding gene on chromosome 19q13.11, encoding Protein LSM14 homolog A (Q8ND56). Essential for formation of P-bodies, cytoplasmic structures that provide storage sites for translationally inactive mRNAs and protect them from degradation.

Sm-like proteins were identified in a variety of organisms based on sequence homology with the Sm protein family (see SNRPD2; 601061). Sm-like proteins contain the Sm sequence motif, which consists of 2 regions separated by a linker of variable length that folds as a loop. The Sm-like proteins are thought to form a stable heteromer present in tri-snRNP particles, which are important for pre-mRNA splicing.

Source: NCBI Gene 26065 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 66 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• MANE Select transcript: NM_015578

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24489
Approved symbol	LSM14A
Name	LSM14A mRNA processing body assembly factor
Location	19q13.11
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP434D1335, RAP55A, RAP55
Ensembl gene	ENSG00000257103
Ensembl biotype	protein_coding
OMIM	610677
Entrez	26065

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 17 protein_coding, 2 retained_intron, 1 non_stop_decay, 1 nonsense_mediated_decay

ENST00000433627, ENST00000540746, ENST00000544216, ENST00000585887, ENST00000586157, ENST00000588582, ENST00000589878, ENST00000590416, ENST00000906056, ENST00000906057, ENST00000906058, ENST00000906059, ENST00000906060, ENST00000906061, ENST00000906062, ENST00000906063, ENST00000914869, ENST00000914870, ENST00000914871, ENST00000914872, ENST00000970126

RefSeq mRNA: 20 — MANE Select: NM_015578 NM_001114093, NM_001384420, NM_001384421, NM_001384422, NM_001384423, NM_001384424, NM_001384425, NM_001384426, NM_001384427, NM_001384428, NM_001384429, NM_001384430, NM_001384431, NM_001384432, NM_001384433, NM_001384434, NM_001384435, NM_001384436, NM_001384437, NM_015578

CCDS: CCDS12435, CCDS46040, CCDS92582

Canonical transcript exons

ENST00000544216 — 10 exons

Exon	Start	End
ENSE00002220844	34194478	34194641
ENSE00002224076	34172504	34172763
ENSE00002233723	34196634	34196763
ENSE00002235635	34208929	34209051
ENSE00002451634	34219391	34219573
ENSE00002529180	34221507	34221738
ENSE00003554641	34215124	34215300
ENSE00003559485	34227365	34229288
ENSE00003582251	34215596	34215661
ENSE00003784317	34219706	34219877

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 86.5988 / max 1145.3604, expressed in 1827 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
175105	74.2909	1827
175107	4.5367	1453
175102	4.0142	1559
175106	0.7805	411
175104	0.7540	473
175103	0.7352	447
175108	0.6583	404
175101	0.4203	204
208774	0.4088	174

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	98.26	gold quality
ganglionic eminence	UBERON:0004023	97.51	gold quality
monocyte	CL:0000576	97.50	gold quality
leukocyte	CL:0000738	97.42	gold quality
endometrium	UBERON:0001295	97.33	gold quality
placenta	UBERON:0001987	97.17	gold quality
stromal cell of endometrium	CL:0002255	97.12	gold quality
islet of Langerhans	UBERON:0000006	96.94	gold quality
calcaneal tendon	UBERON:0003701	96.92	gold quality
lymph node	UBERON:0000029	96.86	gold quality
skeletal muscle tissue	UBERON:0001134	96.77	gold quality
ovary	UBERON:0000992	96.64	gold quality
bone marrow	UBERON:0002371	96.64	gold quality
vermiform appendix	UBERON:0001154	96.62	gold quality
left ovary	UBERON:0002119	96.51	gold quality
smooth muscle tissue	UBERON:0001135	96.44	gold quality
right ovary	UBERON:0002118	96.35	gold quality
colonic epithelium	UBERON:0000397	96.32	gold quality
endocervix	UBERON:0000458	96.32	gold quality
uterine cervix	UBERON:0000002	96.30	gold quality
popliteal artery	UBERON:0002250	96.24	gold quality
tibial artery	UBERON:0007610	96.24	gold quality
muscle tissue	UBERON:0002385	96.18	gold quality
right lung	UBERON:0002167	96.14	gold quality
body of uterus	UBERON:0009853	96.13	gold quality
tonsil	UBERON:0002372	96.09	gold quality
muscle of leg	UBERON:0001383	96.08	gold quality
lower esophagus	UBERON:0013473	96.08	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.08	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.07	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.22

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

177 targeting LSM14A, 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-8485	100.00	77.57	4731
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-1184	99.99	68.19	1458
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-548AT-5P	99.96	70.83	2666

Literature-anchored findings (GeneRIF, showing 8)

• this protein family has evolved a common and fundamental role in the control of mRNA translation. Human RAP55A is an autoantigen detected in the serum of patients with primary biliary cirrhosis (PBC). (PMID:18723115)
• RAP55 is important for the assembly of cytoplasmic mRNP granules and that PRMT1 is required for RAP55A to localize to P-bodies. (PMID:22614839)
• LSm14A is a processing body-associated sensor of viral nucleic acids that initiates cellular antiviral response in the early phase of viral infection. (PMID:22745163)
• The NS1 protein of influenza A virus interacts with cellular processing bodies and stress granules through RNA-associated protein 55 (RAP55) during virus infection. (PMID:22973032)
• RAP55/LSM14 binds directly the tubulin and that is implicated in the process of the mitotic spindle stabilization (PMID:26339800)
• Excessive iron and alpha-synuclein oligomer in brain commonly contributed to pure apathy of PD through potential mechanism of oxidative stress. (PMID:26940028)
• alpha-synuclein p.A53V homozygous mutation leads to a distinct phenotype of progressive parkinsonism and cognitive decline, commonly observed in patients with SNCA missense mutation or multiplications (PMID:28666710)
• Nonstructural Protein NSs Hampers Cellular Antiviral Response through LSm14A during Severe Fever with Thrombocytopenia Syndrome Virus Infection. (PMID:34244294)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	lsm14aa	ENSDARG00000006600
danio_rerio	lsm14ab	ENSDARG00000100553
mus_musculus	Lsm14a	ENSMUSG00000066568
rattus_norvegicus	Lsm14a	ENSRNOG00000021133
drosophila_melanogaster	tral	FBGN0041775
caenorhabditis_elegans	car-1	WBGENE00012484

Paralogs (1): LSM14B (ENSG00000149657)

Protein

Protein identifiers

Protein LSM14 homolog A — Q8ND56 (reviewed: Q8ND56)

Alternative names: Protein FAM61A, Protein SCD6 homolog, Putative alpha-synuclein-binding protein, RNA-associated protein 55A

All UniProt accessions (4): A0A096LP11, Q8ND56, I3L4Q1, K7EMZ9

UniProt curated annotations — full annotation on UniProt →

Function. Essential for formation of P-bodies, cytoplasmic structures that provide storage sites for translationally inactive mRNAs and protect them from degradation. Acts as a repressor of mRNA translation. May play a role in mitotic spindle assembly.

Subunit / interactions. Component of a ribonucleoprotein (RNP) complex. Interacts with DDX6. Interacts with EIF4ENIF1/4E-T; promoting EIF4ENIF1/4E-T localization to P-bodies. Interacts (via FFD box) with EDC4.

Subcellular location. Cytoplasm. P-body. Cytoskeleton. Spindle. Stress granule.

Domain organisation. The LSM14 domain and the RGG repeats are required for accumulation in P-bodies, and the region containing the FDF motif is responsible for cytoplasmic retention.

Similarity. Belongs to the LSM14 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8ND56-1	1, AlphaSNBP(A)	yes
Q8ND56-2	2, AlphaSNBP(B)
Q8ND56-3	3

RefSeq proteins (20): NP_001107565, NP_001371349, NP_001371350, NP_001371351, NP_001371352, NP_001371353, NP_001371354, NP_001371355, NP_001371356, NP_001371357, NP_001371358, NP_001371359, NP_001371360, NP_001371361, NP_001371362, NP_001371363, NP_001371364, NP_001371365, NP_001371366, NP_056393* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010920	LSM_dom_sf	Homologous_superfamily
IPR019050	FDF_dom	Domain
IPR025609	Lsm14-like_N	Domain
IPR025761	FFD_box	Domain
IPR025762	DFDF	Domain
IPR025768	TFG_box	Domain
IPR047575	Sm	Domain

Pfam: PF09532, PF12701

UniProt features (43 total): modified residue 9, mutagenesis site 7, compositionally biased region 6, strand 5, region of interest 3, domain 2, splice variant 2, sequence variant 2, short sequence motif 2, initiator methionine 1, chain 1, sequence conflict 1, turn 1, helix 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6F9W	X-RAY DIFFRACTION	2.62

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8ND56-F1	60.11	0.16

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 (9): 2, 178, 182, 183, 192, 194, 216, 227, 401

Mutagenesis-validated functional residues (7):

Position	Phenotype
22	abolished interaction with eif4enif1/4e-t without affecting interaction with ddx6; when associated with e-29.
29	abolished interaction with eif4enif1/4e-t without affecting interaction with ddx6; when associated with e-22.
296–298	abolished interaction with ddx6.
305	abolished interaction with ddx6.
369–371	does not affect interaction with ddx6.
394–397	abolished interaction with ddx6.
396	abolished interaction with ddx6.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 286 (showing top): GOBP_CHROMOSOME_ORGANIZATION, GOBP_P_BODY_ASSEMBLY, GOBP_RESPONSE_TO_PEPTIDE, SP3_Q3, MORF_SNRP70, MORF_UBE2I, GOBP_RESPONSE_TO_TYPE_I_INTERFERON, GENTILE_RESPONSE_CLUSTER_D3, CACCAGC_MIR138, MODULE_503, GOBP_NEGATIVE_REGULATION_OF_TRANSLATION, GOBP_TRANSLATION, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_REGULATION_OF_IMMUNE_RESPONSE

GO Biological Process (8): negative regulation of translation (GO:0017148), P-body assembly (GO:0033962), stress granule assembly (GO:0034063), RIG-I signaling pathway (GO:0039529), defense response to virus (GO:0051607), positive regulation of type I interferon-mediated signaling pathway (GO:0060340), mitotic spindle assembly (GO:0090307), regulation of translation (GO:0006417)

GO Molecular Function (6): double-stranded DNA binding (GO:0003690), RNA binding (GO:0003723), double-stranded RNA binding (GO:0003725), single-stranded RNA binding (GO:0003727), mRNA binding (GO:0003729), protein binding (GO:0005515)

GO Cellular Component (9): P-body (GO:0000932), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoplasmic stress granule (GO:0010494), cytoplasmic ribonucleoprotein granule (GO:0036464), mitotic spindle (GO:0072686), ribonucleoprotein complex (GO:1990904), spindle (GO:0005819), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA binding	3
translation	2
membraneless organelle assembly	2
cytoplasmic ribonucleoprotein granule	2
cellular anatomical structure	2
cytoplasm	2
intracellular membraneless organelle	2
regulation of translation	1
negative regulation of gene expression	1
negative regulation of protein metabolic process	1
cytoplasmic pattern recognition receptor signaling pathway	1
defense response	1
response to virus	1
positive regulation of cytokine-mediated signaling pathway	1
positive regulation of innate immune response	1
type I interferon-mediated signaling pathway	1
regulation of type I interferon-mediated signaling pathway	1
mitotic sister chromatid segregation	1
mitotic spindle organization	1
spindle assembly	1
mitotic nuclear division	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
DNA binding	1
nucleic acid binding	1
binding	1
intracellular anatomical structure	1
ribonucleoprotein granule	1
spindle	1
protein-containing complex	1
microtubule cytoskeleton	1

Protein interactions and networks

STRING

1816 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LSM14A	DDX6	P26196	994
LSM14A	EDC3	Q96F86	986
LSM14A	EDC4	Q6P2E9	936
LSM14A	EIF4ENIF1	Q9NRA8	928
LSM14A	LSM1	O15116	862
LSM14A	DCP2	Q8IU60	845
LSM14A	PATL1	Q86TB9	835
LSM14A	XRN1	Q8IZH2	826
LSM14A	DCP1A	Q9NPI6	814
LSM14A	UBA2	Q9UBT2	771
LSM14A	CPEB1	Q9BZB8	757
LSM14A	HNRNPU	Q00839	721
LSM14A	LSM2	Q9Y333	719
LSM14A	CNOT1	A5YKK6	706
LSM14A	PABPC1	P11940	701

IntAct

134 interactions, top by confidence:

A	B	Type	Score
MED21	MED19	psi-mi:“MI:0914”(association)	0.880
PRMT8	SYNCRIP	psi-mi:“MI:0914”(association)	0.830
DDX6	YBX1	psi-mi:“MI:0915”(physical association)	0.820
CDK19	MED19	psi-mi:“MI:0914”(association)	0.770
DDX6	RPS3	psi-mi:“MI:0915”(physical association)	0.690
C1QBP	DDX6	psi-mi:“MI:0915”(physical association)	0.620
DDX6	RPLP0	psi-mi:“MI:0915”(physical association)	0.620
DDX6	HSP90AA1	psi-mi:“MI:0915”(physical association)	0.540
KIF2C	KIF2A	psi-mi:“MI:0914”(association)	0.530
LIN28B	ELAVL2	psi-mi:“MI:0914”(association)	0.530
RPS3	ZNF316	psi-mi:“MI:0914”(association)	0.530
ERBB2	HAX1	psi-mi:“MI:0914”(association)	0.530
DDX6	MCRIP1	psi-mi:“MI:0914”(association)	0.510
Lsm14a	DDX6	psi-mi:“MI:0915”(physical association)	0.400
C1QBP	RPS3	psi-mi:“MI:0915”(physical association)	0.400
EIF4ENIF1	RPLP0	psi-mi:“MI:0915”(physical association)	0.400
EIF4ENIF1	PABPC1	psi-mi:“MI:0915”(physical association)	0.400
EIF4ENIF1	MCRIP1	psi-mi:“MI:0915”(physical association)	0.400
FXR2	LSM14A	psi-mi:“MI:0915”(physical association)	0.400
LSM14A	MYCBP2	psi-mi:“MI:0915”(physical association)	0.370
SORT1	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
	TBKBP1	psi-mi:“MI:0914”(association)	0.350
	AURKA	psi-mi:“MI:0914”(association)	0.350
PHACTR3	KCNK3	psi-mi:“MI:0914”(association)	0.350

BioGRID (345): LSM14A (Affinity Capture-MS), LSM14A (Affinity Capture-MS), LSM14A (Affinity Capture-MS), LSM14A (Affinity Capture-MS), LSM14A (Affinity Capture-MS), LSM14A (Affinity Capture-MS), LSM14A (Affinity Capture-MS), LSM14A (Affinity Capture-MS), LSM14A (Affinity Capture-MS), LSM14A (Affinity Capture-MS), LSM14A (Affinity Capture-MS), LSM14A (Affinity Capture-RNA), LSM14A (Affinity Capture-MS), LSM14A (Affinity Capture-MS), LSM14A (Affinity Capture-MS)

ESM2 similar proteins: A0A8M2, A0JMU8, A1L1K8, A5D7H5, B9DFV2, E1BUG7, F4JP52, G1SW77, G3X9Z4, O08719, O15234, O94913, Q0V898, Q1LVV0, Q2T9I5, Q32NW2, Q3MHF8, Q498K9, Q566L7, Q5CZI8, Q5JVS0, Q5R4R4, Q5T8P6, Q5TYQ8, Q659C4, Q68FI1, Q6AXS5, Q6NVR8, Q6NZN0, Q6PKG0, Q8AVJ2, Q8CGC4, Q8K2F8, Q8K3W3, Q8K3X0, Q8NC51, Q8ND56, Q91W18, Q91W39, Q96D71

Diamond homologs: A0A8M2, P45978, Q3MHF8, Q498K9, Q566L7, Q5R4R4, Q68FI1, Q6NVR8, Q8AVJ2, Q8CGC4, Q8K2F8, Q8ND56, Q9BX40, Q9C658, Q9FH77, Q9HGL3, Q9XW17, Q9YH12

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
Adipogenesis	6	9.6×	9e-03
Transcriptional regulation of white adipocyte differentiation	7	9.3×	4e-03
Infectious disease	15	3.8×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of translation	8	11.4×	2e-04
RNA splicing	9	5.8×	5e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — UCEC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1552 predictions. Top by Δscore:

Variant	Effect	Δscore
19:34172761:AAGGT:A	donor_loss	1.0000
19:34172762:AGGT:A	donor_loss	1.0000
19:34172763:GGT:G	donor_loss	1.0000
19:34172764:GTAC:G	donor_loss	1.0000
19:34194472:T:TA	acceptor_gain	1.0000
19:34194476:A:AG	acceptor_gain	1.0000
19:34194476:AGTTC:A	acceptor_gain	1.0000
19:34194477:G:GT	acceptor_gain	1.0000
19:34194477:GT:G	acceptor_gain	1.0000
19:34194477:GTT:G	acceptor_gain	1.0000
19:34194477:GTTC:G	acceptor_gain	1.0000
19:34194477:GTTCG:G	acceptor_gain	1.0000
19:34194639:CAGG:C	donor_loss	1.0000
19:34194640:AGG:A	donor_loss	1.0000
19:34194641:GGT:G	donor_loss	1.0000
19:34194642:G:GA	donor_loss	1.0000
19:34215278:A:T	donor_gain	1.0000
19:34215594:A:AG	acceptor_gain	1.0000
19:34215595:G:GG	acceptor_gain	1.0000
19:34215595:GCT:G	acceptor_gain	1.0000
19:34215658:GTAG:G	donor_gain	1.0000
19:34219697:T:TA	acceptor_gain	1.0000
19:34219700:TCTTA:T	acceptor_loss	1.0000
19:34219701:CTTAG:C	acceptor_loss	1.0000
19:34219702:TTAG:T	acceptor_loss	1.0000
19:34219703:TAGA:T	acceptor_loss	1.0000
19:34219704:A:AG	acceptor_gain	1.0000
19:34219704:A:G	acceptor_loss	1.0000
19:34219705:G:GG	acceptor_gain	1.0000
19:34219705:GA:G	acceptor_gain	1.0000

AlphaMissense

3010 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:34172661:T:C	Y7H	1.000
19:34172665:T:A	I8N	1.000
19:34172667:G:C	G9R	1.000
19:34172667:G:T	G9C	1.000
19:34172668:G:A	G9D	1.000
19:34172668:G:T	G9V	1.000
19:34172670:A:C	S10R	1.000
19:34172671:G:T	S10I	1.000
19:34172672:C:A	S10R	1.000
19:34172672:C:G	S10R	1.000
19:34172677:T:A	I12N	1.000
19:34172677:T:C	I12T	1.000
19:34172677:T:G	I12S	1.000
19:34172679:A:C	S13R	1.000
19:34172681:C:A	S13R	1.000
19:34172681:C:G	S13R	1.000
19:34172683:T:A	L14H	1.000
19:34172683:T:C	L14P	1.000
19:34172683:T:G	L14R	1.000
19:34172686:T:A	I15N	1.000
19:34172686:T:G	I15S	1.000
19:34172688:T:C	S16P	1.000
19:34172689:C:A	S16Y	1.000
19:34172689:C:G	S16C	1.000
19:34172689:C:T	S16F	1.000
19:34172694:G:C	A18P	1.000
19:34172701:T:A	I20N	1.000
19:34172701:T:C	I20T	1.000
19:34172701:T:G	I20S	1.000
19:34172703:C:A	R21S	1.000

dbSNP variants (sampled 300 via entrez): RS1000025390 (19:34217304 GTTGT>G), RS1000026471 (19:34178147 C>T), RS1000065349 (19:34186538 G>A), RS1000082426 (19:34172440 C>CGCCGCT), RS1000127260 (19:34229291 C>T), RS1000212360 (19:34192935 C>A,T), RS1000228513 (19:34191473 G>C,T), RS1000273413 (19:34184545 G>A), RS1000337018 (19:34197930 G>A), RS1000348028 (19:34214126 G>A), RS1000354530 (19:34197786 C>A,T), RS1000439343 (19:34190537 C>A,G), RS1000463202 (19:34177810 T>A), RS1000532259 (19:34173503 G>A), RS1000545605 (19:34207353 T>C)

Disease associations

OMIM: gene MIM:610677 | 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

7 associations (top):

Study	Trait	p-value
GCST004904_204	Body mass index	2.000000e-10
GCST005359_26	Disease progression in age-related macular degeneration	3.000000e-06
GCST006291_98	Spherical equivalent or myopia (age of diagnosis)	8.000000e-09
GCST90002390_652	Mean corpuscular hemoglobin	6.000000e-13
GCST90002391_114	Mean corpuscular hemoglobin concentration	1.000000e-12
GCST90002405_546	Reticulocyte count	6.000000e-11
GCST90002406_501	Reticulocyte fraction of red cells	2.000000e-12

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0008336	disease progression measurement
EFO:0004847	age at onset
EFO:0004527	mean corpuscular hemoglobin
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0007986	reticulocyte count

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: yes

ChEMBL targets (1): CHEMBL5724639 (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: 1,538 (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
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.57	Kd	269	nM	MOLIBRESIB
6.19	IC50	640	nM	MOLIBRESIB
5.95	Kd	1123	nM	CHEMBL5653589
5.95	ED50	1123	nM	CHEMBL5653589

PubChem BioAssay actives

3 with measured affinity, of 9 total; 2 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
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179208: Binding affinity against LSM14A (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.2690	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148671: Binding affinity to human LSM14A incubated for 45 mins by Kinobead based pull down assay	kd	1.1227	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	4
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
bisphenol A	decreases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, decreases reaction	1
cobaltous chloride	decreases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
coumarin	increases phosphorylation	1
tamibarotene	decreases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
CGP 52608	increases reaction, affects binding	1
bisphenol S	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Caffeine	affects phosphorylation	1
Carbamazepine	affects expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Lead	decreases expression	1
Methapyrilene	decreases methylation	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651713	Binding	Binding affinity to human LSM14A incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

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