NLRP7

Summary

NLRP7 (NLR family pyrin domain containing 7, HGNC:22947) is a protein-coding gene on chromosome 19q13.42, encoding NACHT, LRR and PYD domains-containing protein 7 (Q8WX94). Inhibits CASP1/caspase-1-dependent IL1B secretion.

This gene encodes a member of the NACHT, leucine rich repeat, and PYD containing (NLRP) protein family. It has an N-terminal pyrin domain, followed by a NACHT domain, a NACHT-associated domain (NAD), and a C-terminal leucine-rich repeat (LRR) region. NLRP proteins are implicated in the activation of proinflammatory caspases through multiprotein complexes called inflammasomes. This gene may act as a feedback regulator of caspase-1-dependent interleukin 1-beta secretion. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 199713 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hydatidiform mole, recurrent, 1 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 242 total — 12 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 9
• MANE Select transcript: NM_001127255

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22947
Approved symbol	NLRP7
Name	NLR family pyrin domain containing 7
Location	19q13.42
Locus type	gene with protein product
Status	Approved
Aliases	PYPAF3, NOD12, PAN7, CLR19.4
Ensembl gene	ENSG00000167634
Ensembl biotype	protein_coding
OMIM	609661
Entrez	199713

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 nonsense_mediated_decay

ENST00000328092, ENST00000340844, ENST00000586379, ENST00000587103, ENST00000587844, ENST00000588756, ENST00000590030, ENST00000590659, ENST00000592784

RefSeq mRNA: 4 — MANE Select: NM_001127255 NM_001127255, NM_001405531, NM_139176, NM_206828

CCDS: CCDS12912, CCDS33109, CCDS46183

Canonical transcript exons

ENST00000592784 — 11 exons

Exon	Start	End
ENSE00001176556	54930499	54930666
ENSE00001176566	54934489	54934659
ENSE00001176572	54936261	54936431
ENSE00001176598	54940931	54941005
ENSE00001328512	54938888	54940466
ENSE00001374528	54927605	54927775
ENSE00001389281	54938044	54938241
ENSE00002448002	54923515	54923872
ENSE00002507500	54933569	54933739
ENSE00002853254	54947469	54947530
ENSE00003492789	54941435	54941750

Expression profiles

Bgee: expression breadth broad, 49 present calls, max score 85.14.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.7001 / max 545.6393, expressed in 39 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
182671	0.7001	39

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.14	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.07	gold quality
granulocyte	CL:0000094	69.44	gold quality
testis	UBERON:0000473	64.43	gold quality
blood	UBERON:0000178	63.74	gold quality
left testis	UBERON:0004533	63.11	gold quality
right testis	UBERON:0004534	62.54	gold quality
bone marrow cell	CL:0002092	59.27	silver quality
duodenum	UBERON:0002114	58.72	gold quality
vermiform appendix	UBERON:0001154	56.29	gold quality
lymph node	UBERON:0000029	55.74	gold quality
leukocyte	CL:0000738	54.58	gold quality
spleen	UBERON:0002106	54.40	gold quality
monocyte	CL:0000576	53.35	gold quality
placenta	UBERON:0001987	52.65	gold quality
rectum	UBERON:0001052	51.77	gold quality
bone marrow	UBERON:0002371	51.76	silver quality
tonsil	UBERON:0002372	50.19	gold quality
gall bladder	UBERON:0002110	46.01	gold quality
mucosa of transverse colon	UBERON:0004991	43.38	silver quality
urinary bladder	UBERON:0001255	42.50	gold quality
colonic epithelium	UBERON:0000397	41.11	gold quality
sural nerve	UBERON:0015488	40.82	gold quality
cortical plate	UBERON:0005343	39.85	gold quality
smooth muscle tissue	UBERON:0001135	39.17	gold quality
lung	UBERON:0002048	38.93	gold quality
stromal cell of endometrium	CL:0002255	38.71	gold quality
small intestine	UBERON:0002108	38.32	gold quality
muscle tissue	UBERON:0002385	37.94	silver quality
lower esophagus mucosa	UBERON:0035834	37.84	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-3929	no	237.98
E-ANND-3	no	1.71

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting NLRP7, 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-150-5P	99.99	66.69	1976
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-2116-3P	99.74	64.32	889
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-532-3P	99.34	65.76	1195
HSA-MIR-3179	98.22	65.90	1445
HSA-MIR-146B-3P	97.83	65.29	782
HSA-MIR-921	97.09	66.45	562
HSA-MIR-339-5P	96.73	66.01	820
HSA-MIR-7973	96.48	65.54	502

Literature-anchored findings (GeneRIF, showing 40)

• Up-regulation of NALP7 is associated with testicular seminomas (PMID:15596043)
• PYPAF3 is a feedback regulator of interleukin-1beta secretion, and PYPAF2 and PYPAF3, together with PYNOD, constitute an anti-inflammatory subgroup of PYRIN-containing apoptotic protease-activating factor-1-like proteins (PMID:15817483)
• Stable expression of PYPAF3 (NALP7) abrogated the ability of cells to produce interleukin-1beta in response to lipopolysaccharide. (PMID:15817483)
• Five mutations in the maternal gene NALP7 in individuals with familial and recurrent Hydatidiform mole (PMID:16462743)
• Mutation my be involed in the inflammatory and apoptoic pathways in hydatidiform moles. (PMID:16501554)
• Role of NALP7 in apoptosis and inflammation pinpoints previously unrecognized pathways that could directly or indirectly underlie the abnormal methylation of imprinted genes in hydatidiform moles tissues. (PMID:16874523)
• study reports a first stop codon, c.295G>T (p.Glu99X) and a missense mutation, c.1970A>T (p.Asp657Val) in NLRP7 in two sisters with familial recurrent hydatidiform moles (PMID:17579354)
• Our findings firmly establish that NLRP7 mutations are a major cause of biparental hydatidiform moles and confirm presence of a complex pattern of imprinting abnormalities in BiHM tissues. (PMID:18039680)
• NLRP7 expression was positive in cancer cells in 7 cases. There was a statistical relationship between the depth of tumor invasion and NLRP7 expression. NLRP7 expression showed a trend for being associated with poor prognosis. (PMID:18751440)
• Ten new mutations in NLRP7 are responsible for several types of hydatidiform moles. (PMID:19066229)
• Screened a large series of women with familial recurrent hydatidiform mole. 16 different mutations were identified in the study, 13 of which were novel. (PMID:19246479)
• the presence of two founder mutations in the Indian population (mutations have no consequences on male reproduction) (PMID:19650864)
• NMR resonance assignments of the human NLRP7 (PMID:19888692)
• genetic analysis of NLRP7 in 2 cases of recurrent complete hydatidiform mole: (1) patient has novel homozygous mutation in exon 8 of NLRP7; (2) patient had androgenetic CHM with no apparent mutations in NLRP7 (PMID:20870286)
• previous and current data show the association of NLRP7 mutations with several types of hydatidiform moles and with triploid spontaneous abortions (PMID:21421271)
• a new homozygous NLRP7 mutation in patients with recurrent hydatidiform mole (PMID:21439709)
• three new protein-truncating mutations in NLRP7 are described; data suggest that patients with a single defective allele have better reproductive outcomes than patients with two defective alleles (PMID:21507883)
• study of familial and sporadic recurrent hydatidiform moles; report of the first Tunisian patients: 2 sisters with homozygous NLRP7 mutations (p.E570X) and 1 sporadic case with no mutation in NLRP7 (PMID:21623199)
• The presence of NLRP7 mutations was demonstrated in two patients with recurrent spontaneous abortions, and some rare non-synonymous variants (NSVs), present in the general population, were found to be associated with recurrent reproductive wastage. (PMID:21659348)
• Data report the presence of three novel NLRP7 variants that were found only in patients with sporadic hydatidiform moles but not in 100 controls from the Senegalese general population. (PMID:21948117)
• NLRP7 co-localizes with the Golgi and the microtubule-organizing center and is associated with microtubules. This suggests that NLRP7 mutations may affect cytokine secretion by interfering, directly or indirectly, with their trafficking. (PMID:22025618)
• women with mutations in NLRP7 cannot achieve a normal pregnancy and each molar pregnancy carries risk of malignant transformation (PMID:22130487)
• NLRP7 mutations may lead to familial recurrent hydatidiform mole. (PMID:22169519)
• NLRP7 mutations do not represent a major cause of complete hydatidiform moles of proven androgenetic origin. (PMID:22315435)
• Activation of NLRP7 promoted ASC-dependent caspase-1 activation, IL-1beta and IL-18 maturation, and restriction of intracellular bacterial replication, but not caspase-1-independent secretion of the proinflammatory cytokines IL-6 and tumor necrosis factor-alpha. (PMID:22361007)
• As homozygous NLRP7 mutations are associated with recurrent hydatidiform mole or conception loss, the heterozygous state could represent a risk factor for nonrecurrent mole. (PMID:22646272)
• genetic association studies in two Egyptian families: This study expands the known cases of mutations in NLRP7 associated with recurrent hydatidiform mole. [CASE REPORT] (PMID:22770628)
• Observations suggest that although NLRP7 and C6orf221 mutations are related to diploid biparental FRHMs, neither of these genes, nor NLRP2, are related to diploid HMs with biparental contributions to the molar genome. (PMID:22909446)
• Both NLRP7 and KHDC3L are involved in setting or maintaining the appropriate imprint within the ovum in women with familial recurrent hydatidiform mole. (PMID:23125094)
• Histopathological features of biparental complete hydatidiform moles in women with NLRP7 mutations. (PMID:23201303)
• Similarities between two recurrent hydatidiform moles (RHM) causative genes, KHDC3L and NLRP7, in their subcellular localization, parental contribution to the HM tissues caused by them, and the presence of several founder mutations. (PMID:23232697)
• In a Mexican population with recurrent hytadiform mole, 60% presented homozygous p.L750V mutations, 25% were compound heterozygotes for p.L750V mutation and the p.E340K variant, and 15% were heterozygous for p.E340K variant. (PMID:23354651)
• A SNP within NLRP7 is associated with recurrent miscarriage. (PMID:23360675)
• these findings suggest that neither mutations nor variants in NLRP7 and C6orf221 are major factors contributing to the risk of these types of pregnancy complications. (PMID:23515668)
• Two novel NLRP7-truncating mutations are associated with familial recurrent hydatidiform mole (PMID:23880596)
• A statistically non-significant tendency of non-synonymous variants in NLRP7 more frequent in women with familial hydatidiform mole and in women with female family members with hydatidiform mole or non-mole miscarriage. (PMID:23963444)
• NLRP7 thus appears to function in chromatin reprogramming and DNA methylation in the germline or early embryonic development.NLRP7 affects trophoblast lineage differentiation, binds to overexpressed YY1 and alters CpG methylation. (PMID:24105472)
• The absence of mutations in women with Androgenetic complete hydatidiform moles supports a role for NLRP7 or KHDC3L in Biparental hydatidiform moles only. (PMID:24105752)
• NLRP7, depending on the severity of its mutations, regulates the imprinted expression of p57KIP2 and consequently the balance between tissue differentiation and proliferation during early human development. (PMID:25097207)
• NLRP7 and KHDC3L localize to the cytoskeleton and are predominant at the cortical region in growing oocytes. (PMID:25358348)

Cross-species orthologs

0 orthologs

Paralogs (20): NLRP2 (ENSG00000022556), NLRP1 (ENSG00000091592), NOD1 (ENSG00000106100), NLRC5 (ENSG00000140853), NLRP12 (ENSG00000142405), NLRP14 (ENSG00000158077), NLRP4 (ENSG00000160505), NLRX1 (ENSG00000160703), NLRP3 (ENSG00000162711), NOD2 (ENSG00000167207), NLRC3 (ENSG00000167984), NLRP5 (ENSG00000171487), 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 7 — Q8WX94 (reviewed: Q8WX94)

Alternative names: Nucleotide-binding oligomerization domain protein 12, PYRIN-containing APAF1-like protein 3

All UniProt accessions (5): Q8WX94, K7EP54, K7EPY3, K7ER92, K7ERG0

UniProt curated annotations — full annotation on UniProt →

Function. Inhibits CASP1/caspase-1-dependent IL1B secretion.

Subunit / interactions. Directly interacts with CASP1 and IL1B.

Tissue specificity. Expressed in numerous tissues including uterus and ovary, with low levels in heart and brain. Not detected in skeletal muscle.

Disease relevance. Hydatidiform mole, recurrent, 1 (HYDM1) [MIM:231090] A disorder characterized by excessive trophoblast development that produces a growing mass of tissue inside the uterus at the beginning of a pregnancy. It leads to abnormal pregnancies with no embryo, and cystic degeneration of the chorionic villi. The disease is caused by variants affecting the gene represented in this entry.

Induction. By bacterial lipopolysaccharides (LPS) and IL1B/interleukin-1 beta in peripheral blood mononuclear cells.

Similarity. Belongs to the NLRP family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8WX94-1	1	yes
Q8WX94-2	2
Q8WX94-3	3

RefSeq proteins (4): NP_001120727, NP_001392460, NP_631915, NP_996611 (=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 (45 total): sequence variant 19, repeat 9, helix 7, domain 2, splice variant 2, chain 1, region of interest 1, compositionally biased region 1, binding site 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
9LQ2	ELECTRON MICROSCOPY	3.58
9LQ4	ELECTRON MICROSCOPY	4.12
2KM6	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WX94-F1	82.25	0.41

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): 178–185

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 102 (showing top): GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, GOBP_NEGATIVE_REGULATION_OF_INTERLEUKIN_1_PRODUCTION, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_SPINDLE_LOCALIZATION, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_INTERLEUKIN_1_PRODUCTION, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_PROTEIN_MATURATION, GOBP_PRODUCTION_OF_MOLECULAR_MEDIATOR_INVOLVED_IN_INFLAMMATORY_RESPONSE, GOBP_CYTOKINE_PRODUCTION, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_RESPONSE_TO_INTERLEUKIN_1

GO Biological Process (6): negative regulation of protein processing (GO:0010955), negative regulation of interleukin-1 beta production (GO:0032691), regulation of inflammatory response (GO:0050727), cellular response to lipopolysaccharide (GO:0071222), cellular response to interleukin-1 (GO:0071347), negative regulation of cytokine production involved in inflammatory response (GO:1900016)

GO Molecular Function (7): ATP binding (GO:0005524), aspartic-type endopeptidase inhibitor activity (GO:0019828), interleukin-1 binding (GO:0019966), identical protein binding (GO:0042802), caspase binding (GO:0089720), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein processing	1
negative regulation of proteolysis	1
regulation of protein processing	1
negative regulation of protein maturation	1
interleukin-1 beta production	1
regulation of interleukin-1 beta production	1
negative regulation of interleukin-1 production	1
inflammatory response	1
regulation of defense response	1
regulation of response to external stimulus	1
response to lipopolysaccharide	1
cellular response to molecule of bacterial origin	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
response to interleukin-1	1
cellular response to cytokine stimulus	1
negative regulation of cytokine production	1
cytokine production involved in inflammatory response	1
regulation of cytokine production involved in inflammatory response	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
aspartic-type endopeptidase activity	1
endopeptidase inhibitor activity	1
growth factor binding	1
cytokine binding	1
protein binding	1
protease binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1115 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NLRP7	NLRC4	Q9NPP4	995
NLRP7	NLRP6	P59044	988
NLRP7	NLRP1	Q9C000	986
NLRP7	NLRP3	Q96P20	984
NLRP7	NLRP12	P59046	980
NLRP7	KHDC3L	Q587J8	918
NLRP7	AIM2	O14862	909
NLRP7	MEFV	O15553	904
NLRP7	CASP1	P29466	880
NLRP7	PYCARD	Q9ULZ3	876
NLRP7	NLRC5	Q86WI3	799
NLRP7	NAIP	Q13075	787
NLRP7	PYDC1	Q8WXC3	781
NLRP7	IFI16	Q16666	763
NLRP7	NLRP2	Q9NX02	742

IntAct

10 interactions, top by confidence:

A	B	Type	Score
NLRP2	NLRP7	psi-mi:“MI:0915”(physical association)	0.460
NLRP2	NLRP7	psi-mi:“MI:0403”(colocalization)	0.460
NLRP5	NLRP7	psi-mi:“MI:0915”(physical association)	0.400
TLE6	NLRP7	psi-mi:“MI:0915”(physical association)	0.400
PADI6	NLRP7	psi-mi:“MI:0915”(physical association)	0.400
KHDC3L	NLRP7	psi-mi:“MI:0915”(physical association)	0.400
OOEP	NLRP7	psi-mi:“MI:0915”(physical association)	0.400
ZBED3	NLRP7	psi-mi:“MI:0915”(physical association)	0.400
DEF8	APAF1	psi-mi:“MI:0914”(association)	0.350

BioGRID (169): ZBTB16 (Two-hybrid), ZBTB16 (Affinity Capture-Western), ZBTB16 (Co-purification), NLRP7 (Two-hybrid), ZBTB16 (Co-localization), NLRP7 (Biochemical Activity), NLRP7 (Affinity Capture-MS), NLRP7 (Affinity Capture-Western), CASP1 (Affinity Capture-Western), NLRP7 (Affinity Capture-Western), IL1B (Affinity Capture-Western), USP10 (Affinity Capture-Western), NLRP7 (Affinity Capture-Western), ARG1 (Affinity Capture-MS), ATP5A1 (Affinity Capture-MS)

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: A0A386CAB9, A1Z198, A6QLE5, B0FPE9, D4A523, D9I2F9, D9I2G1, D9I2G3, D9I2G4, D9I2H0, E9Q5R7, O15553, P10775, P13489, P29315, P59044, P59045, P59046, Q0GKD5, Q288C4, Q2LKU9, Q2LKV2, Q2LKV5, Q2LKW6, Q3TKR3, Q63035, Q647I9, Q66X01, Q66X03, Q66X19, Q6B966, Q7RTR0, Q86W24, Q86W25, Q86W26, Q86W28, Q8BU40, Q8C6J9, Q8CCN1, Q8HZP9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	12
Likely pathogenic	1
Uncertain significance	144
Likely benign	17
Benign	10

Top pathogenic / likely-pathogenic (13)

Variant ID	HGVS	Classification
1074591	NM_001127255.2(NLRP7):c.1072C>T (p.Gln358Ter)	Pathogenic
1584	NM_001127255.2(NLRP7):c.352+1G>A	Pathogenic
1586	NM_001127255.2(NLRP7):c.2077C>T (p.Arg693Trp)	Pathogenic
1587	NM_001127255.2(NLRP7):c.2078G>C (p.Arg693Pro)	Pathogenic
1589	NM_001127255.2(NLRP7):c.1294C>T (p.Arg432Ter)	Pathogenic
1592	NM_001127255.2(NLRP7):c.1193T>G (p.Leu398Arg)	Pathogenic
1593	NM_001127255.2(NLRP7):c.1951C>T (p.Pro651Ser)	Pathogenic
4293511	NM_001127255.2(NLRP7):c.818G>A (p.Trp273Ter)	Pathogenic
812700	NM_001127255.2(NLRP7):c.1857_1858delAC (p.Lys619Asnfs)	Pathogenic
97796	NM_001127255.2(NLRP7):c.336dup (p.Glu113Glyfs)	Pathogenic
97807	NM_001127255.2(NLRP7):c.939_952dup (p.Tyr318Cysfs)	Pathogenic
997708	NM_001127255.2(NLRP7):c.1224_1232delGCGGGGCGCinsT (p.Arg409Alafs)	Pathogenic
2571601	NM_001127255.2(NLRP7):c.277+1G>A	Likely pathogenic

SpliceAI

1375 predictions. Top by Δscore:

Variant	Effect	Δscore
19:54930580:AAGT:A	donor_gain	1.0000
19:54933567:A:AC	donor_gain	1.0000
19:54933568:C:CC	donor_gain	1.0000
19:54933568:CA:C	donor_gain	1.0000
19:54933602:AAG:A	donor_gain	1.0000
19:54933602:AAGC:A	donor_gain	1.0000
19:54933741:T:A	acceptor_loss	1.0000
19:54934482:GACTT:G	donor_loss	1.0000
19:54934483:ACTTA:A	donor_loss	1.0000
19:54934484:CTT:C	donor_loss	1.0000
19:54934485:TTACG:T	donor_loss	1.0000
19:54934486:TA:T	donor_loss	1.0000
19:54934487:A:AC	donor_gain	1.0000
19:54934488:C:A	donor_loss	1.0000
19:54934488:C:CT	donor_gain	1.0000
19:54934488:CG:C	donor_gain	1.0000
19:54934488:CGA:C	donor_gain	1.0000
19:54934488:CGACA:C	donor_gain	1.0000
19:54934655:CCAAC:C	acceptor_gain	1.0000
19:54934656:CAAC:C	acceptor_gain	1.0000
19:54934656:CAACC:C	acceptor_gain	1.0000
19:54934657:AAC:A	acceptor_gain	1.0000
19:54934658:AC:A	acceptor_gain	1.0000
19:54934658:ACCTG:A	acceptor_loss	1.0000
19:54934659:CC:C	acceptor_gain	1.0000
19:54934659:CCTG:C	acceptor_loss	1.0000
19:54934660:C:CA	acceptor_loss	1.0000
19:54934660:C:CC	acceptor_gain	1.0000
19:54934661:T:C	acceptor_loss	1.0000
19:54936256:CCCA:C	donor_loss	1.0000

AlphaMissense

6841 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:54938118:G:C	S685R	0.990
19:54938118:G:T	S685R	0.990
19:54938120:T:G	S685R	0.990
19:54941638:A:G	F25S	0.988
19:54941634:T:A	K26N	0.987
19:54941634:T:G	K26N	0.987
19:54936354:A:G	L736P	0.985
19:54938183:A:G	W664R	0.985
19:54938183:A:T	W664R	0.985
19:54933643:G:C	N856K	0.982
19:54933643:G:T	N856K	0.982
19:54941637:G:C	F25L	0.979
19:54941637:G:T	F25L	0.979
19:54941639:A:G	F25L	0.979
19:54930664:A:G	L882S	0.978
19:54939964:A:C	S285R	0.977
19:54939964:A:T	S285R	0.977
19:54939966:T:G	S285R	0.977
19:54933659:A:G	L851P	0.976
19:54940268:T:A	K184I	0.976
19:54941662:A:G	L17P	0.974
19:54933572:A:G	L880S	0.972
19:54933653:A:G	L853S	0.970
19:54940265:G:A	T185I	0.970
19:54933627:C:A	G862W	0.968
19:54938181:C:A	W664C	0.968
19:54938181:C:G	W664C	0.968
19:54939923:A:T	V299D	0.968
19:54930580:A:G	L910S	0.965
19:54930654:G:C	C885W	0.963

dbSNP variants (sampled 300 via entrez): RS1000090386 (19:54926162 G>A), RS1000109704 (19:54940321 G>A), RS1000212863 (19:54938967 G>A), RS1000400928 (19:54947631 C>T), RS1000528233 (19:54926404 A>G), RS1000542413 (19:54929768 G>A), RS1000653941 (19:54927033 T>A), RS1000715189 (19:54949497 G>A), RS1000784440 (19:54946196 C>T), RS1001138000 (19:54925417 A>G), RS1001177509 (19:54941188 C>T), RS1001257323 (19:54931977 G>A), RS1001305940 (19:54936392 G>T), RS1001337628 (19:54935657 G>A), RS1001342810 (19:54945208 A>C)

Disease associations

OMIM: gene MIM:609661 | disease phenotypes: MIM:231090, MIM:621471

GenCC curated gene-disease

Disease	Classification	Inheritance
hydatidiform mole, recurrent, 1	Strong	Autosomal recessive
complete hydatidiform mole	Supportive	Autosomal recessive

Mondo (4): hydatidiform mole, recurrent, 1 (MONDO:0009273), oocyte/zygote/embryo maturation arrest 25 (MONDO:0980964), hydatidiform mole (MONDO:0006248), complete hydatidiform mole (MONDO:0016785)

Orphanet (2): Complete hydatidiform mole (Orphanet:254688), Hydatidiform mole (Orphanet:99927)

HPO phenotypes

9 total (9 of 9 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0005268	Miscarriage
HP:0008222	Female infertility
HP:0011462	Young adult onset
HP:0020003	Embryo developmental arrest
HP:0032192	Hydatidiform mole
HP:0032468	History of stillbirth
HP:0033712	Repeated implantation failure

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001725_62	Inflammatory bowel disease	7.000000e-11

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D006828	Hydatidiform Mole	C04.557.465.955.416.812; C04.850.908.416.750; C12.050.703.720.949.416.875

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

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression	3
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
triphenyl phosphate	affects expression	1
sodium arsenite	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	decreases expression	1
Arsenic	affects methylation	1
Cadmium	decreases expression	1
Methapyrilene	increases methylation	1
Methyl Methanesulfonate	decreases expression	1
Nickel	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Zinc	increases expression	1
Aflatoxin B1	increases methylation	1

Cellosaurus cell lines

1 cell lines: 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A7MC	FAHZUi001-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01630954	PHASE4	UNKNOWN	A Comparison of Single Versus Double Evacuation for Treatment of Hydatidiform Mole
NCT00003702	PHASE3	COMPLETED	Methotrexate Compared With Dactinomycin in Treating Patients With Gestational Trophoblastic Neoplasia
NCT01535053	PHASE3	COMPLETED	Dactinomycin or Methotrexate in Treating Patients With Low-Risk Gestational Trophoblastic Neoplasia
NCT01984099	PHASE3	COMPLETED	RCT on the Efficacy of Methotrexate for the Prevention of GTD
NCT04756713	PHASE3	UNKNOWN	Second Uterine Evacuation for Low-risk Gestational Trophoblastic Neoplasia
NCT00521118	PHASE2	COMPLETED	Second Curettage in Treating Patients With Persistent Non-metastatic Gestational Trophoblastic Tumors
NCT00190918	PHASE2	COMPLETED	A Trial for Patients With Gestational Trophoblastic Disease
NCT01008501	Not specified	ACTIVE_NOT_RECRUITING	Study of the Genetic and Epigenetic Causes of Recurrent Hydatidiform Moles
NCT02892877	Not specified	RECRUITING	The French National Reference Centre of GTD
NCT03785574	Not specified	RECRUITING	Study of Different Therapeutic Strategies in Hydatidiform Mole With Lung Nodule
NCT05516810	Not specified	ACTIVE_NOT_RECRUITING	The Accuracy of Ultrasound Diagnosis of Hydatidiform Moles
NCT05637892	Not specified	NOT_YET_RECRUITING	A Cohort Study of Hydatidiform Mole
NCT07202728	Not specified	RECRUITING	A Multi-center Cohort Study of Hydatidiform Mole in China (CN-HM-01)