NLRP13

Summary

NLRP13 (NLR family pyrin domain containing 13, HGNC:22937) is a protein-coding gene on chromosome 19q13.43, encoding NACHT, LRR and PYD domains-containing protein 13 (Q86W25). Involved in inflammation.

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. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 126204 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 194 total
• MANE Select transcript: NM_176810

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22937
Approved symbol	NLRP13
Name	NLR family pyrin domain containing 13
Location	19q13.43
Locus type	gene with protein product
Status	Approved
Aliases	NOD14, PAN13, CLR19.7
Ensembl gene	ENSG00000173572
Ensembl biotype	protein_coding
OMIM	609660
Entrez	126204

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000342929, ENST00000588751, ENST00000850974

RefSeq mRNA: 2 — MANE Select: NM_176810 NM_001321057, NM_176810

CCDS: CCDS33119, CCDS82401

Canonical transcript exons

ENST00000342929 — 11 exons

Exon	Start	End
ENSE00001178568	55895945	55896119
ENSE00001178573	55902035	55902205
ENSE00001244088	55924590	55924658
ENSE00001244095	55924967	55925035
ENSE00001244101	55931993	55932336
ENSE00001244121	55923914	55923979
ENSE00001246395	55898770	55898937
ENSE00001246404	55904942	55905112
ENSE00001246409	55907792	55907956
ENSE00001372246	55910563	55910733
ENSE00001388480	55911706	55913293

Expression profiles

Bgee: expression breadth broad, 42 present calls, max score 99.48.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	99.48	gold quality
secondary oocyte	CL:0000655	98.83	gold quality
colonic epithelium	UBERON:0000397	88.73	gold quality
bone marrow cell	CL:0002092	83.84	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.39	gold quality
epithelium of nasopharynx	UBERON:0001951	61.10	gold quality
tonsil	UBERON:0002372	59.82	gold quality
buccal mucosa cell	CL:0002336	59.49	gold quality
sperm	CL:0000019	54.37	gold quality
endothelial cell	CL:0000115	51.47	gold quality
skeletal muscle tissue	UBERON:0001134	48.44	gold quality
bone marrow	UBERON:0002371	48.19	gold quality
layer of synovial tissue	UBERON:0007616	46.63	gold quality
muscle tissue	UBERON:0002385	45.60	gold quality
middle temporal gyrus	UBERON:0002771	45.14	gold quality
urinary bladder	UBERON:0001255	44.49	gold quality
liver	UBERON:0002107	44.37	gold quality
amniotic fluid	UBERON:0000173	43.46	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
ventral tegmental area	UBERON:0002691	43.35	gold quality
cartilage tissue	UBERON:0002418	43.08	gold quality
nipple	UBERON:0002030	42.98	gold quality
subthalamic nucleus	UBERON:0001906	42.75	gold quality
urethra	UBERON:0000057	42.54	gold quality
dorsal root ganglion	UBERON:0000044	42.43	gold quality
body of tongue	UBERON:0011876	42.42	gold quality
pharyngeal mucosa	UBERON:0000355	42.38	gold quality
sural nerve	UBERON:0015488	42.30	gold quality
superior vestibular nucleus	UBERON:0007227	42.28	gold quality
mammalian vulva	UBERON:0000997	42.24	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.42

Regulation

Is transcription factor: no

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), NLRP7 (ENSG00000167634), NLRC3 (ENSG00000167984), NLRP5 (ENSG00000171487), NLRP6 (ENSG00000174885), CIITA (ENSG00000179583), NLRP8 (ENSG00000179709), NLRP11 (ENSG00000179873), NLRP10 (ENSG00000182261), NLRP9 (ENSG00000185792), PYDC2 (ENSG00000253548)

Protein

Protein identifiers

NACHT, LRR and PYD domains-containing protein 13 — Q86W25 (reviewed: Q86W25)

Alternative names: Nucleotide-binding oligomerization domain protein 14

All UniProt accessions (2): Q86W25, A0A0C4DGQ4

UniProt curated annotations — full annotation on UniProt →

Function. Involved in inflammation.

Similarity. Belongs to the NLRP family.

RefSeq proteins (2): NP_001307986, NP_789780* (*=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: PF00560, PF02758, PF05729, PF13516, PF17776, PF17779

UniProt features (14 total): repeat 7, domain 2, sequence variant 2, chain 1, binding site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86W25-F1	81.19	0.38

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): 235–242

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 17 (showing top): GOBP_INFLAMMATORY_RESPONSE, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_INFLAMMATORY_RESPONSE, GOBP_REGULATION_OF_DEFENSE_RESPONSE, GOMF_ADENYL_NUCLEOTIDE_BINDING, MIR1251_3P, MIR7154_3P, MIR1306_5P, GSE13485_DAY3_VS_DAY21_YF17D_VACCINE_PBMC_DN, DESCARTES_MAIN_FETAL_LENS_FIBRE_CELLS, NOTCH3_TARGET_GENES, GSE26495_PD1HIGH_VS_PD1LOW_CD8_TCELL_UP, JONES_OVARY_OOCYTE, GOMF_PURINE_NUCLEOTIDE_BINDING

GO Biological Process (1): regulation of inflammatory response (GO:0050727)

GO Molecular Function (3): ATP binding (GO:0005524), 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
inflammatory response	1
regulation of defense response	1
regulation of response to external stimulus	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate 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

517 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NLRP13	MEFV	O15553	755
NLRP13	NLRC4	Q9NPP4	693
NLRP13	CASP1	P29466	638
NLRP13	DPY19L3	Q6ZPD9	507
NLRP13	PRPSAP1	Q14558	490
NLRP13	PPP1R3G	B7ZBB8	462
NLRP13	CHST10	O43529	457
NLRP13	NAIP	Q13075	457
NLRP13	ZC3H8	Q8N5P1	452
NLRP13	MTMR1	Q13613	443
NLRP13	PRDM13	Q9H4Q3	433
NLRP13	CMTM4	Q8IZR5	425
NLRP13	RAB11FIP5	Q9BXF6	424
NLRP13	AP3B1	O00203	414
NLRP13	SOHLH1	Q5JUK2	410

IntAct

0 interactions, top by confidence:

BioGRID (7): NLRP13 (Co-fractionation), SHMT2 (Co-fractionation), NLRP13 (Affinity Capture-MS), NLRP13 (Affinity Capture-MS), NLRP13 (Cross-Linking-MS (XL-MS)), STX7 (Cross-Linking-MS (XL-MS)), NLRP13 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2JMD5, A1Z198, A3QJZ6, A3QJZ7, A6NGN4, D9I2F9, D9I2G1, D9I2G3, D9I2G4, D9I2H0, E9Q5G7, H0Y7S4, O60809, O60810, O60811, O60813, O95521, O95522, P0DUQ1, P0DUQ2, P78395, Q0GKD5, Q288C4, Q2LKU9, Q2LKV5, Q2LKW6, Q3TKR3, Q3UWY1, Q5SWL7, Q5SWL8, Q5TYX0, Q5VT98, Q5VTA0, Q5VWM3, Q5VWM4, Q5VWM6, Q5VXH4, Q5VXH5, Q66X05, Q66X19

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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	155
Likely benign	18
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1799 predictions. Top by Δscore:

Variant	Effect	Δscore
19:55898765:CTCA:C	donor_loss	1.0000
19:55898766:TCA:T	donor_loss	1.0000
19:55898767:CA:C	donor_loss	1.0000
19:55898768:A:AC	donor_gain	1.0000
19:55898768:A:T	donor_loss	1.0000
19:55898768:AC:A	donor_gain	1.0000
19:55898769:C:CC	donor_gain	1.0000
19:55898769:CC:C	donor_gain	1.0000
19:55898769:CCCAA:C	donor_gain	1.0000
19:55901252:A:C	acceptor_gain	1.0000
19:55902033:A:AC	donor_gain	1.0000
19:55902034:C:CC	donor_gain	1.0000
19:55902034:CTT:C	donor_gain	1.0000
19:55904940:A:AC	donor_gain	1.0000
19:55904940:ACT:A	donor_gain	1.0000
19:55904941:C:CC	donor_gain	1.0000
19:55904941:CT:C	donor_gain	1.0000
19:55904941:CTC:C	donor_gain	1.0000
19:55906531:A:AC	donor_gain	1.0000
19:55906532:C:CC	donor_gain	1.0000
19:55906532:CGA:C	donor_gain	1.0000
19:55923910:ACAC:A	donor_loss	1.0000
19:55923911:CA:C	donor_loss	1.0000
19:55923913:C:CT	donor_loss	1.0000
19:55923919:T:TA	donor_gain	1.0000
19:55924586:ACACC:A	donor_loss	1.0000
19:55924587:CA:C	donor_loss	1.0000
19:55924588:A:AT	donor_loss	1.0000
19:55924655:TTCC:T	acceptor_gain	1.0000
19:55924656:TCC:T	acceptor_gain	1.0000

AlphaMissense

6941 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:55932213:C:A	K33N	0.989
19:55932213:C:G	K33N	0.989
19:55932217:A:G	F32S	0.989
19:55912215:G:C	F534L	0.988
19:55912215:G:T	F534L	0.988
19:55912217:A:G	F534L	0.988
19:55910702:A:G	W715R	0.986
19:55910702:A:T	W715R	0.986
19:55913031:G:C	F262L	0.981
19:55913031:G:T	F262L	0.981
19:55913033:A:G	F262L	0.981
19:55913092:G:A	T242I	0.981
19:55910637:G:C	S736R	0.980
19:55910637:G:T	S736R	0.980
19:55910639:T:G	S736R	0.980
19:55896039:A:G	L1013P	0.976
19:55910700:C:A	W715C	0.974
19:55910700:C:G	W715C	0.974
19:55907879:A:G	L787P	0.973
19:55932109:A:G	L68P	0.973
19:55932216:G:C	F32L	0.973
19:55932216:G:T	F32L	0.973
19:55932218:A:G	F32L	0.973
19:55896117:A:G	L987S	0.972
19:55912191:A:C	F542L	0.972
19:55912191:A:T	F542L	0.972
19:55912193:A:G	F542L	0.972
19:55911788:A:G	C677R	0.971
19:55912357:G:T	A487D	0.971
19:55932250:A:G	L21P	0.971

dbSNP variants (sampled 300 via entrez): RS1000028744 (19:55898412 G>T), RS1000076461 (19:55894521 G>C), RS1000193901 (19:55893385 T>C), RS1000195225 (19:55924824 T>A,C), RS1000295613 (19:55920072 A>G), RS1000376441 (19:55929631 G>A), RS1000527025 (19:55914982 A>T), RS1000541021 (19:55910231 G>A), RS1000596780 (19:55925051 A>G), RS1000700682 (19:55920097 T>C), RS1000761888 (19:55906062 G>A), RS1000793926 (19:55920258 C>A), RS1000815397 (19:55920264 C>T), RS1000917490 (19:55932663 G>A,T), RS1000944200 (19:55900618 T>A)

Disease associations

OMIM: gene MIM:609660 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): long QT syndrome (MONDO:0002442)

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001538_32	Immune reponse to smallpox (secreted IFN-alpha)	5.000000e-07
GCST008363_10	Offspring birth weight	3.000000e-12
GCST008876_3	Non-lobar intracerebral hemorrhage (MTAG)	6.000000e-06

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0004873	cytokine measurement
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement
EFO:0010178	non-lobar intracerebral hemorrhage

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547

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

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
clothianidin	decreases expression	1
abrine	increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02513940	PHASE4	COMPLETED	Influence of Testosterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes
NCT03834883	PHASE4	COMPLETED	Reducing the Risk of Drug-Induced QT Interval Lengthening in Women
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04675788	PHASE4	COMPLETED	Novel Approaches for Minimizing Drug-Induced QT Interval Lengthening
NCT01648205	PHASE2	COMPLETED	Long-term Efficacy Study of Sodium Channel Blocker in LQT3 Patients
NCT02412709	PHASE2	UNKNOWN	Long QT Syndrome Screening in Newborns
NCT04581408	PHASE2	COMPLETED	Mutation-specific Therapy for the Long QT Syndrome
NCT00316459	PHASE1	COMPLETED	Study Evaluating the Effects of Multiple Oral Doses of ERB-041 on Cardiac Repolarization in Healthy Subjects
NCT01849003	PHASE1	COMPLETED	Study of the Effect of GS-6615 in Subjects With LQT-3
NCT02365532	PHASE1	COMPLETED	Effect of Oral GS-6615 on Dofetilide-Induced QT Prolongation, Safety, and Tolerability in Healthy Adults
NCT02412098	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Hepatic Function
NCT02441829	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Renal Function
NCT05759962	PHASE1	COMPLETED	Phase 1 Study of LQT-1213 in Healthy Adults
NCT05906732	PHASE1/PHASE2	TERMINATED	Study of LQT-1213 on QTc-induced Prolongation in Healthy Adult Subjects (Part1) and on Congenital Long QT in Patients Diagnosed With Type 2 or 3 Long QT Syndrome (Part 2).
NCT00005176	Not specified	COMPLETED	Long QT Syndrome-Population Genetics and Cardiac Studies
NCT00005250	Not specified	COMPLETED	Linkage Study of Long QT Syndrome In An Amish Kindred
NCT00005367	Not specified	COMPLETED	Epidemiology of Long QTand Asian Sudden Death in Sleep
NCT00221832	Not specified	UNKNOWN	Molecular Genetic Screening and Identification of Congenital Arrhythmogenic Diseases
NCT00292032	Not specified	COMPLETED	Registry of Unexplained Cardiac Arrest
NCT00335036	Not specified	TERMINATED	Pediatric Lead Extractability and Survival Evaluation (PLEASE)
NCT00399412	Not specified	COMPLETED	ECG Signal Collection From Long QT Syndrome, Wide QRS Complexes, Heart Failure, and Cardiac Resynchronization Patients
NCT00488254	Not specified	COMPLETED	The Long QT Syndrome in Pregnancy
NCT00588965	Not specified	COMPLETED	Effect of Beta-blocker Therapy on QTc Response in Exercise and Recovery in Normal Subjects
NCT01705925	Not specified	COMPLETED	Multicenter Evaluation of Children and Young Adults With Genotype Positive Long QT Syndrome
NCT01903564	Not specified	COMPLETED	Fetal and Neonatal Magnetophysiology
NCT02082431	Not specified	COMPLETED	Determine the Incidence of Long QT Amongst a Large Cohort of Subjects Diagnosed With Unilateral or Bilateral Sensorineural Hearing Loss.
NCT02413450	Not specified	ENROLLING_BY_INVITATION	Derivation of Human Induced Pluripotent Stem (iPS) Cells to Heritable Cardiac Arrhythmias
NCT02425189	Not specified	COMPLETED	The Canadian National Long QT Syndrome Registry
NCT02439645	Not specified	TERMINATED	A Registry to Determine the Clinical and Genetic Risk Factors for Torsade De Pointes
NCT02439658	Not specified	UNKNOWN	Genetics of QT Prolongation With Antiarrhythmics
NCT02549664	Not specified	COMPLETED	Exercise in Genetic Cardiovascular Conditions
NCT02581241	Not specified	COMPLETED	Abnormal QT-Response to the Sudden Tachycardia Provoked by Standing in Individuals With Drug-induced Long QT Syndrome
NCT02680080	Not specified	COMPLETED	Effect of Grapefruit on QT Interval in Healthy Volunteers and Patients With Congenital Long QT Syndrome
NCT02775513	Not specified	UNKNOWN	Metabolism of Patients With Genetically Caused Cardiac Arrhythmia
NCT02814981	Not specified	UNKNOWN	Hydroxyzine and Risk of Prolongation of QT Interval
NCT02876380	Not specified	COMPLETED	Prospective Identification of Long QT Syndrome in Fetal Life
NCT03182777	Not specified	COMPLETED	Safety of Local Dental Anesthesia in Patients With Cardiac Channelopathies
NCT03544918	Not specified	COMPLETED	Prevalence of Congenital Long QT Syndrome and Acquired QT Prolongation in a Hospital Cohort
NCT03642405	Not specified	UNKNOWN	Drug-induced Repolarization ECG Changes
NCT03678311	Not specified	COMPLETED	Long QT Syndrome and Sleep Apnea