NLRP5

Summary

NLRP5 (NLR family pyrin domain containing 5, HGNC:21269) is a protein-coding gene on chromosome 19q13.43, encoding NACHT, LRR and PYD domains-containing protein 5 (P59047). Component of the subcortical maternal complex (SCMC), a multiprotein complex that plays a key role in early embryonic development.

The protein encoded by this gene belongs to the NALP protein family. Members of the NALP protein family typically contain a NACHT domain, a NACHT-associated domain (NAD), a C-terminal leucine-rich repeat (LRR) region, and an N-terminal pyrin domain (PYD). Expression of this gene is restricted to the oocyte. A mouse gene that encodes a maternal oocyte protein, similar to this encoded protein, is required for normal early embryogenesis.

Source: NCBI Gene 126206 — RefSeq curated summary.

At a glance

• Gene–disease (curated): oocyte/zygote/embryo maturation arrest 19 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 307 total — 4 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 3
• MANE Select transcript: NM_001433705

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21269
Approved symbol	NLRP5
Name	NLR family pyrin domain containing 5
Location	19q13.43
Locus type	gene with protein product
Status	Approved
Aliases	PYPAF8, MATER, PAN11, CLR19.8
Ensembl gene	ENSG00000171487
Ensembl biotype	protein_coding
OMIM	609658
Entrez	126206

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 nonsense_mediated_decay

ENST00000390649, ENST00000597673, ENST00000850973

RefSeq mRNA: 1 — MANE Select: NM_001433705 NM_001433705

CCDS: CCDS12938

Canonical transcript exons

ENST00000850973 — 15 exons

Exon	Start	End
ENSE00001052740	56050418	56050588
ENSE00001052741	56053638	56053808
ENSE00001052742	56038025	56038195
ENSE00001115571	56058240	56058410
ENSE00001115588	56040922	56041092
ENSE00001168395	56032611	56032781
ENSE00001242324	56033542	56033709
ENSE00001242332	56026913	56028509
ENSE00001318507	56015742	56015798
ENSE00001323043	56008788	56008853
ENSE00001508542	56003736	56004095
ENSE00002518231	56019342	56019398
ENSE00002519351	56020375	56020431
ENSE00003716144	56061396	56061810
ENSE00004283100	55986775	55986821

Expression profiles

Bgee: expression breadth broad, 22 present calls, max score 98.68.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.68	gold quality
oocyte	CL:0000023	97.49	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.61	gold quality
buccal mucosa cell	CL:0002336	55.47	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	45.87	gold quality
lateral nuclear group of thalamus	UBERON:0002736	45.65	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
endometrium	UBERON:0001295	42.55	gold quality
bone marrow cell	CL:0002092	41.99	gold quality
epithelium of nasopharynx	UBERON:0001951	41.69	gold quality
skin of hip	UBERON:0001554	41.55	silver quality
vastus lateralis	UBERON:0001379	41.41	gold quality
ventral tegmental area	UBERON:0002691	41.40	gold quality
quadriceps femoris	UBERON:0001377	41.37	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
subthalamic nucleus	UBERON:0001906	41.03	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
dorsal plus ventral thalamus	UBERON:0001897	40.97	gold quality
Brodmann (1909) area 23	UBERON:0013554	40.94	gold quality
mammary duct	UBERON:0001765	40.80	gold quality
amniotic fluid	UBERON:0000173	40.69	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
biceps brachii	UBERON:0001507	40.57	gold quality
myocardium	UBERON:0002349	40.45	gold quality
gingival epithelium	UBERON:0001949	40.43	gold quality
germinal epithelium of ovary	UBERON:0001304	40.33	gold quality
esophagus squamous epithelium	UBERON:0006920	40.29	gold quality
medulla oblongata	UBERON:0001896	40.28	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	40.27	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.92

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1

miRNA regulators (miRDB)

19 targeting NLRP5, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-642A-5P	99.51	65.10	1152
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-4721	99.26	66.05	818
HSA-MIR-4999-3P	99.11	65.55	424
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-4691-5P	98.41	66.77	1343
HSA-MIR-6792-3P	98.41	66.86	1359
HSA-MIR-5691	98.23	67.02	1335
HSA-MIR-6805-3P	98.23	67.02	1334
HSA-MIR-3921	97.81	67.45	1431
HSA-MIR-3614-3P	97.81	67.15	582
HSA-MIR-4653-5P	97.22	67.72	1429
HSA-MIR-1226-5P	96.50	65.28	643
HSA-MIR-5586-3P	95.51	67.00	805

Literature-anchored findings (GeneRIF, showing 15)

• characterization of the MATER gene and its protein; this provides a basis for investigating their clinical implications in autoimmune premature ovarian failure and infertility in women (PMID:11925379)
• NALP5 appears to be a tissue-specific autoantigen involved in hypoparathyroidism in patients with APS-1. Autoantibodies against NALP5 appear to be highly specific and may be diagnostic for this prominent component of APS-1 (PMID:18322283)
• The nuclear, nucleolar and mitochondrial localization hints at a possible role in RNA processing and the metabolic activity of the cell. (PMID:19192343)
• MATER protein interacts with tPKCepsilon in cumulus cells under physiological conditions. (PMID:19542546)
• NLRP5 mutation is associated with multilocus imprinting disorders and reproductive wastage. (PMID:26323243)
• expression of MATER and NOX4 proteins are closely related to the follicular development and ovulation with particular regard for ovarian aging (PMID:27515505)
• PSMG4 and NLRP5 appear of particular interest as they were found to be associated with more than one clinical phenotype and are implicated in biological processes considered relevant to the pathophysiology of MS. Also, PSMG4 p.W99R and NLRP5 p.R761L were found to correlate with an earlier age of MS clinical onset. Our data suggests PSMG4 and NLPR5 as potential targets for the development of modifying therapies for MS. (PMID:28501589)
• NLRP2 and NLRP5 are novel mutant genes responsible for human early embryonic arrest. (PMID:30877238)
• The identification of two novel maternal-effect variants of NLRP5 associated with poly-abortivity and s multi-locus imprinting disturbances (MLID) adds further evidence to its role in the maintenance of genomic imprinting in early embryos. (PMID:31829238)
• A novel homozygous variant in NLRP5 is associate with human early embryonic arrest in a consanguineous Chinese family. (PMID:32222962)
• Novel pathogenic variants in NLRP7, NLRP5, and PADI6 in patients with recurrent hydatidiform moles and reproductive failure. (PMID:33583041)
• Deubiquitination and Activation of the NLRP3 Inflammasome by UCHL5 in HCV-Infected Cells. (PMID:34431717)
• Novel mutations in NLRP5 and PATL2 cause female infertility characterized by primarily oocyte maturation abnormality and consequent early embryonic arrest. (PMID:35091966)
• Mutations in OOEP and NLRP5 identified in infertile patients with early embryonic arrest. (PMID:35946397)
• The maternal protein NLRP5 stabilizes UHRF1 in the cytoplasm: implication for the pathogenesis of multilocus imprinting disturbance. (PMID:38868925)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Nlrp5	ENSMUSG00000015721
rattus_norvegicus	Nlrp5	ENSRNOG00000022994

Paralogs (20): NLRP2 (ENSG00000022556), NLRP1 (ENSG00000091592), NOD1 (ENSG00000106100), NLRC5 (ENSG00000140853), NLRP12 (ENSG00000142405), NLRP14 (ENSG00000158077), NLRP4 (ENSG00000160505), NLRX1 (ENSG00000160703), NLRP3 (ENSG00000162711), NOD2 (ENSG00000167207), NLRP7 (ENSG00000167634), NLRC3 (ENSG00000167984), NLRP13 (ENSG00000173572), NLRP6 (ENSG00000174885), CIITA (ENSG00000179583), NLRP8 (ENSG00000179709), NLRP11 (ENSG00000179873), NLRP10 (ENSG00000182261), NLRP9 (ENSG00000185792), PYDC2 (ENSG00000253548)

Protein

Protein identifiers

NACHT, LRR and PYD domains-containing protein 5 — P59047 (reviewed: P59047)

Alternative names: Mater protein homolog, Maternal Antigen that Embryos Require

All UniProt accessions (2): P59047, M0R0W4

UniProt curated annotations — full annotation on UniProt →

Function. Component of the subcortical maternal complex (SCMC), a multiprotein complex that plays a key role in early embryonic development. The SCMC complex is a structural constituent of cytoplasmic lattices, which consist in fibrous structures found in the cytoplasm of oocytes and preimplantation embryos. They are required to store maternal proteins critical for embryonic development, such as proteins that control epigenetic reprogramming of the preimplantation embryo, and prevent their degradation or activation. Required for the localization of cortical granules to the cortex of oocytes, via association with the cortical actin scaffold. Required for cortical actin clearance prior to oocyte exocytosis and prevention of polyspermy. Involved in regulating post-fertilization Ca(2+) release and endoplasmic reticulum storage (ER) storage via regulation of cellular localization. May be involved in the localization of mitochondria to the cytoplasm and perinuclear region in oocytes and early stage embryos, independent of its role in CPL formation.

Subunit / interactions. Component of the subcortical maternal complex (SCMC), at least composed of NLRP5, KHDC3, OOEP, and TLE6 isoform 1. Within the complex, interacts with OOEP, KHDC3L and TLE6. The SCMC may facilitate translocation of its components between the nuclear and cytoplasmic compartments. As part of the SCMC interacts with the SCMC-associated protein ZBED3. As part of the SCMC interacts with the SCMC-associated protein CFL1/Cofilin-1. Interacts with PRKCE. Interacts with TUBB3 at cytoskeleton microtubules.

Subcellular location. Cytoplasm. Cytoplasmic vesicle. Secretory vesicle. Cortical granule. Mitochondrion. Nucleus. Nucleolus. Golgi apparatus.

Tissue specificity. Expressed in cumulus cells (at protein level). Highly abundant in oocytes and early embryos, however poorly expressed in somatic tissues such as the liver and spinal cord.

Post-translational modifications. Phosphorylated by PRKCE.

Disease relevance. Oocyte/zygote/embryo maturation arrest 19 (OZEMA19) [MIM:620333] An autosomal recessive female infertility disorder characterized by reduced fertilization rate, oocyte maturation arrest at germinal vesicle stage, and early embryonic arrest. The disease is caused by variants affecting the gene represented in this entry. NLRP5 variants have been found in a spectrum of phenotypes characterized by aberrant methylation of multiple imprinted loci, a condition known as multi-locus imprinting defect or multi-locus imprinting disturbance (MLID). MLID-related phenotype spectrum ranges from intrauterine death to different types of imprinting disorders, including Beckwith-Wiedemann syndrome (BWS), Silver-Russell syndrome (SRS), and non-specific developmental and behavioral manifestations. MLID has also been observed in individuals without overt clinical manifestations. Recurrent pregnancy loss has been reported in healthy women carrying NLRP5 variants.

Similarity. Belongs to the NLRP family.

RefSeq proteins (1): NP_001420634* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001611	Leu-rich_rpt	Repeat
IPR004020	DAPIN	Domain
IPR007111	NACHT_NTPase	Domain
IPR011029	DEATH-like_dom_sf	Homologous_superfamily
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR041075	NOD1/2_WH	Domain
IPR041267	NLRP_HD2	Domain
IPR050637	NLRP_innate_immun_reg	Family

Pfam: PF02758, PF05729, PF13516, PF17776, PF17779

UniProt features (141 total): helix 47, strand 32, sequence variant 32, repeat 13, compositionally biased region 4, turn 3, mutagenesis site 3, domain 2, sequence conflict 2, chain 1, region of interest 1, binding site 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
8X7V	ELECTRON MICROSCOPY	3.01
8X7W	ELECTRON MICROSCOPY	3.36
9L4L	ELECTRON MICROSCOPY	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P59047-F1	77.44	0.40

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 (1): 286–293

Mutagenesis-validated functional residues (3):

Position	Phenotype
60–63	impaired formation of the subcortical maternal complex (scmc).
71	impaired formation of the subcortical maternal complex (scmc).
107	impaired formation of the subcortical maternal complex (scmc).

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 98 (showing top): GOBP_SINGLE_FERTILIZATION, GOBP_NEGATIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_INFLAMMATORY_RESPONSE, GOCC_SECRETORY_GRANULE, GOBP_SPINDLE_LOCALIZATION, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_EXOCYTOSIS, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1, GOBP_ACTIN_FILAMENT_ORGANIZATION, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_SECRETION, GOBP_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_REGULATION_OF_CELL_DIVISION, GOBP_CALCIUM_ION_REGULATED_EXOCYTOSIS, GOBP_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS

GO Biological Process (10): exocytosis (GO:0006887), actin filament organization (GO:0007015), regulation of protein localization (GO:0032880), positive regulation of embryonic development (GO:0040019), regulation of inflammatory response (GO:0050727), establishment of spindle localization (GO:0051293), regulation of cell division (GO:0051302), establishment of organelle localization (GO:0051656), cortical granule exocytosis (GO:0060471), protein storage (GO:0140089)

GO Molecular Function (5): ATP binding (GO:0005524), tubulin binding (GO:0015631), structural constituent of cytoplasmic lattice (GO:0140094), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (11): nucleus (GO:0005634), nucleolus (GO:0005730), cytoplasm (GO:0005737), mitochondrion (GO:0005739), Golgi apparatus (GO:0005794), cytosol (GO:0005829), cell cortex (GO:0005938), cortical granule (GO:0060473), subcortical maternal complex (GO:0106333), cytoplasmic lattice (GO:0140095), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	5
intracellular membrane-bounded organelle	3
intracellular membraneless organelle	2
cellular anatomical structure	2
vesicle-mediated transport	1
secretion by cell	1
vesicle fusion to plasma membrane	1
actin cytoskeleton organization	1
supramolecular fiber organization	1
intracellular protein localization	1
regulation of localization	1
embryo development	1
regulation of embryonic development	1
positive regulation of developmental process	1
positive regulation of multicellular organismal process	1
inflammatory response	1
regulation of defense response	1
regulation of response to external stimulus	1
microtubule cytoskeleton organization	1
establishment of localization in cell	1
spindle localization	1
establishment of organelle localization	1
regulation of cellular process	1
cell division	1
establishment of localization	1
organelle localization	1
calcium-ion regulated exocytosis	1
prevention of polyspermy	1
nutrient storage	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
cytoskeletal protein binding	1
structural molecule activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
nuclear lumen	1
intracellular anatomical structure	1
endomembrane system	1
cell periphery	1

Protein interactions and networks

STRING

1028 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NLRP5	OOEP	A6NGQ2	949
NLRP5	TLE6	Q9H808	932
NLRP5	KHDC3L	Q587J8	912
NLRP5	PADI6	Q6TGC4	860
NLRP5	AIRE	O43918	781
NLRP5	GDF9	O60383	750
NLRP5	ZBED3	Q96IU2	721
NLRP5	ZAR1	Q86SH2	719
NLRP5	MEFV	O15553	665
NLRP5	DDC	P20711	659
NLRP5	CASR	P41180	625
NLRP5	BMP15	O95972	584
NLRP5	PTPRN	Q16849	583
NLRP5	ZP1	P60852	535
NLRP5	PATL2	C9JE40	524

IntAct

13 interactions, top by confidence:

A	B	Type	Score
NLRP5	TLE6	psi-mi:“MI:0915”(physical association)	0.400
NLRP5	KHDC3L	psi-mi:“MI:0915”(physical association)	0.400
NLRP5	OOEP	psi-mi:“MI:0915”(physical association)	0.400
TLE6	NLRP5	psi-mi:“MI:0915”(physical association)	0.400
NLRP5	NLRP7	psi-mi:“MI:0915”(physical association)	0.400
MATR3	BCLAF3	psi-mi:“MI:0914”(association)	0.350
NLRP2	RBBP6	psi-mi:“MI:0914”(association)	0.350
NLRP3	PHRF1	psi-mi:“MI:0914”(association)	0.350
NLRP5	BECN1	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350

BioGRID (16): NLRP5 (Co-fractionation), DECR1 (Affinity Capture-MS), BECN1 (Affinity Capture-MS), BAG2 (Affinity Capture-MS), STIP1 (Affinity Capture-MS), LRRC1 (Affinity Capture-MS), NLRP5 (Affinity Capture-MS), NLRP5 (Affinity Capture-MS), NLRP5 (Affinity Capture-MS), NLRP5 (Affinity Capture-MS), NLRP5 (Affinity Capture-MS), NLRP5 (Affinity Capture-MS), NLRP5 (Affinity Capture-MS), NLRP5 (Affinity Capture-MS), NLRP5 (Co-fractionation)

ESM2 similar proteins: A1Z198, A6QLE5, B0FPE9, D4A523, D9I2F9, D9I2G1, D9I2G3, D9I2G4, D9I2H0, E9Q5G7, E9Q5R7, P59045, P59046, P59047, Q0GKD5, Q288C4, Q2LKU9, Q2LKV2, Q2LKV5, Q2LKW6, Q3TKR3, Q3UWY1, Q63035, Q647I9, Q66X01, Q66X03, Q66X05, Q66X19, Q66X22, Q6B966, Q7RTR0, Q7TPX8, Q86W24, Q86W25, Q86W26, Q86W28, Q8BU40, Q8BVP1, Q8C6J9, Q8CCN1

Diamond homologs: A1Z198, A6QLE5, A8Y3R9, B0FPE9, D4A523, D9I2F9, D9I2G1, D9I2G3, D9I2G4, D9I2H0, E9Q5R7, P10775, P13489, P29315, P59044, P59046, P59047, Q0GKD5, Q2LKU9, Q2LKV2, Q2LKV5, Q2LKW6, Q5RAV7, Q63035, Q6B966, Q86W24, Q86W25, Q86W26, Q8CCN1, Q8HXK9, Q8HZP9, Q8R4B8, Q91VI7, Q91WS2, Q96P20, Q9C000, Q9EPB4, Q9I9N6, Q9ULZ3, Q9Y2G2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PRKCE	“up-regulates activity”	NLRP5	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	3
Uncertain significance	174
Likely benign	57
Benign	26

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
2069859	NC_000019.10:g.56008808G>T	Pathogenic
2499459	NC_000019.10:g.56003945C>T	Pathogenic
2499460	NC_000019.10:g.56028314C>T	Pathogenic
2499462	NC_000019.10:g.56058260C>T	Pathogenic
103296	NM_001433705.1(NLRP5):c.-71-3948G>A	Likely pathogenic
3780032	NM_001433705.1(NLRP5):c.-30del	Likely pathogenic
812688	NM_001433705.1(NLRP5):c.2121_2122del (p.Trp708fs)	Likely pathogenic

SpliceAI

2539 predictions. Top by Δscore:

Variant	Effect	Δscore
19:56004091:GAAAA:G	donor_gain	1.0000
19:56004092:AAAAG:A	donor_loss	1.0000
19:56004093:AAAG:A	donor_loss	1.0000
19:56004094:AA:A	donor_gain	1.0000
19:56004095:AG:A	donor_loss	1.0000
19:56004096:G:GG	donor_gain	1.0000
19:56004096:GTAA:G	donor_loss	1.0000
19:56004097:T:G	donor_loss	1.0000
19:56008841:G:GT	donor_gain	1.0000
19:56008842:A:T	donor_gain	1.0000
19:56015740:A:AG	acceptor_gain	1.0000
19:56015740:A:T	acceptor_loss	1.0000
19:56015740:AG:A	acceptor_gain	1.0000
19:56015741:G:GA	acceptor_gain	1.0000
19:56015741:GG:G	acceptor_gain	1.0000
19:56015741:GGA:G	acceptor_gain	1.0000
19:56015741:GGAA:G	acceptor_gain	1.0000
19:56015741:GGAAT:G	acceptor_gain	1.0000
19:56015796:AAGG:A	donor_loss	1.0000
19:56015797:AGG:A	donor_loss	1.0000
19:56015798:GGTGA:G	donor_loss	1.0000
19:56015799:G:GC	donor_loss	1.0000
19:56019340:A:AG	acceptor_gain	1.0000
19:56019341:G:GG	acceptor_gain	1.0000
19:56019341:GA:G	acceptor_gain	1.0000
19:56019341:GAA:G	acceptor_gain	1.0000
19:56019394:ACAAG:A	donor_loss	1.0000
19:56019395:CAAG:C	donor_loss	1.0000
19:56019396:AAG:A	donor_loss	1.0000
19:56019398:GGTGA:G	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000127978 (19:56042970 T>C), RS1000173132 (19:56052786 G>A), RS1000177311 (19:56054066 C>T), RS1000247627 (19:56020926 T>A), RS1000265781 (19:56021327 A>C), RS1000290566 (19:56049754 C>A), RS1000303311 (19:56020742 C>T), RS1000360218 (19:56050948 C>T), RS1000392809 (19:56050712 T>C), RS1000398377 (19:56057168 A>G), RS1000402894 (19:56030048 C>G), RS1000434092 (19:56030231 G>A), RS1000434832 (19:56041685 C>T), RS1000452598 (19:56024748 A>G,T), RS1000467047 (19:56025734 A>C,G)

Disease associations

OMIM: gene MIM:609658 | disease phenotypes: MIM:615774, MIM:620333, MIM:600268

GenCC curated gene-disease

Disease	Classification	Inheritance
oocyte/zygote/embryo maturation arrest 19	Strong	Autosomal recessive
Beckwith-Wiedemann syndrome	Strong	Autosomal recessive

Mondo (5): inherited oocyte maturation defect (MONDO:0014769), oocyte/zygote/embryo maturation arrest 19 (MONDO:0957231), breast ductal adenocarcinoma (MONDO:0005590), Toriello-Lacassie-Droste syndrome (MONDO:0010854), Beckwith-Wiedemann syndrome (MONDO:0007534)

Orphanet (1): Oculoectodermal syndrome (Orphanet:3339)

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0008222	Female infertility
HP:0011462	Young adult onset

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009269_20	Dental caries (decayed and filled deciduous teeth)	5.000000e-06

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D001506	Beckwith-Wiedemann Syndrome	C16.131.077.133; C16.131.260.080; C16.320.180.080; C16.320.447.375
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
C563969	Aplasia Cutis Congenita with Epibulbar Dermoids (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: catalytic receptor — NOD-like receptor family

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation	2
propionaldehyde	decreases expression	1
CGP 52608	affects binding, increases reaction	1
theaflavin-3,3’-digallate	affects expression	1
Calcitriol	increases expression, affects cotreatment	1
Estradiol	affects cotreatment, increases expression	1
Folic Acid	decreases expression	1
Progesterone	affects cotreatment, increases expression	1
Smoke	increases expression	1
Testosterone	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00945009	PHASE3	ACTIVE_NOT_RECRUITING	Combination Chemotherapy and Surgery in Treating Young Patients With Wilms Tumor
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT01916148	Not specified	AVAILABLE	18F-L-Fluoro-DOPA PET/CT Scan Localization of Focal Pancreatic Lesions in Subjects With Hyperinsulinemic Hypoglycemia
NCT04993235	Not specified	UNKNOWN	Body Perception and Representation in Overgrowth Syndromes, Behavioral Assessment and Neuropsychological Development
NCT05945576	Not specified	RECRUITING	IDMet (RaDiCo Cohort) (RaDiCo-IDMet)
NCT06346418	Not specified	RECRUITING	Maternal Genes and Epimutations: Beckwith-Wiedemann Syndrome & Reproductive Risks
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery