NLRP14

Summary

NLRP14 (NLR family pyrin domain containing 14, HGNC:22939) is a protein-coding gene on chromosome 11p15.4, encoding NACHT, LRR and PYD domains-containing protein 14 (Q86W24). May be involved in inflammation and spermatogenesis.

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). This protein may play a regulatory role in the innate immune system as similar family members belong to the signal-induced multiprotein complex, the inflammasome, that activates the pro-inflammatory caspases, caspase-1 and caspase-5.

Source: NCBI Gene 338323 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 362 total
• MANE Select transcript: NM_176822

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22939
Approved symbol	NLRP14
Name	NLR family pyrin domain containing 14
Location	11p15.4
Locus type	gene with protein product
Status	Approved
Aliases	NOD5, GC-LRR, Nalp-iota, PAN8, CLR11.2
Ensembl gene	ENSG00000158077
Ensembl biotype	protein_coding
OMIM	609665
Entrez	338323

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000299481, ENST00000892206

RefSeq mRNA: 1 — MANE Select: NM_176822 NM_176822

CCDS: CCDS7776

Canonical transcript exons

ENST00000299481 — 12 exons

Exon	Start	End
ENSE00001036885	7058280	7058450
ENSE00001036888	7062333	7062503
ENSE00001188298	7049671	7049838
ENSE00001188304	7070286	7070456
ENSE00001188307	7042388	7043984
ENSE00001216301	7039714	7039785
ENSE00001216309	7071173	7071526
ENSE00001216316	7038566	7038875
ENSE00001299420	7046668	7046832
ENSE00001305134	7057677	7057847
ENSE00001306845	7059894	7060064
ENSE00001526043	7020479	7020770

Expression profiles

Bgee: expression breadth broad, 26 present calls, max score 84.89.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	84.89	gold quality
secondary oocyte	CL:0000655	83.23	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	68.32	gold quality
bone marrow cell	CL:0002092	64.42	silver quality
buccal mucosa cell	CL:0002336	62.39	gold quality
ventricular zone	UBERON:0003053	61.95	gold quality
tendon of biceps brachii	UBERON:0008188	61.51	gold quality
medial globus pallidus	UBERON:0002477	54.04	gold quality
globus pallidus	UBERON:0001875	51.03	gold quality
upper leg skin	UBERON:0004262	50.72	silver quality
sperm	CL:0000019	50.69	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	50.11	gold quality
ganglionic eminence	UBERON:0004023	50.04	silver quality
tendon	UBERON:0000043	48.51	gold quality
colonic epithelium	UBERON:0000397	46.42	gold quality
thymus	UBERON:0002370	45.61	gold quality
nasal cavity mucosa	UBERON:0001826	45.20	gold quality
liver	UBERON:0002107	45.16	gold quality
lower lobe of lung	UBERON:0008949	45.03	silver quality
oviduct epithelium	UBERON:0004804	44.34	silver quality
amniotic fluid	UBERON:0000173	43.65	gold quality
adult mammalian kidney	UBERON:0000082	43.53	gold quality
cortical plate	UBERON:0005343	43.46	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
kidney	UBERON:0002113	42.63	gold quality
duodenum	UBERON:0002114	42.51	gold quality
jejunum	UBERON:0002115	42.26	gold quality
vastus lateralis	UBERON:0001379	42.09	gold quality
quadriceps femoris	UBERON:0001377	42.03	gold quality
heart right ventricle	UBERON:0002080	41.88	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.23

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

20 targeting NLRP14, 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-3924	100.00	72.09	2394
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-567	99.63	68.57	1219
HSA-MIR-6871-3P	99.43	68.85	741
HSA-MIR-297	99.40	69.58	1418
HSA-MIR-4797-5P	99.39	68.01	1354
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-3187-5P	98.36	65.74	1776
HSA-MIR-4773	98.35	67.30	1710
HSA-MIR-1285-3P	97.72	67.02	1932
HSA-MIR-5189-5P	97.72	66.96	1814
HSA-MIR-612	97.26	65.95	1597
HSA-MIR-6860	97.21	66.31	1656
HSA-MIR-4486	96.96	60.61	931
HSA-MIR-4790-3P	96.63	67.08	806
HSA-MIR-6861-5P	96.23	67.19	800

Literature-anchored findings (GeneRIF, showing 4)

• Our data suggest that NALP14 has a function in spermatogenesis and that mutations in this gene might cause spermatogenic failure. (PMID:16931801)
• This study describes conformational stability of native NLRP14 and mutants in their monomeric and dimeric states and compares them to NLRP4, a representative of a native pyrin domain fold. (PMID:25403012)
• Data show that NLRP14 expression was rapidly downregulated after fertilization. (PMID:28423339)
• NLRP14 deficiency causes female infertility with oocyte maturation defects and early embryonic arrest by impairing cytoplasmic UHRF1 abundance. (PMID:38060382)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Nlrp14	ENSMUSG00000016626
rattus_norvegicus	Nlrp14	ENSRNOG00000023847

Paralogs (20): NLRP2 (ENSG00000022556), NLRP1 (ENSG00000091592), NOD1 (ENSG00000106100), NLRC5 (ENSG00000140853), NLRP12 (ENSG00000142405), NLRP4 (ENSG00000160505), NLRX1 (ENSG00000160703), NLRP3 (ENSG00000162711), NOD2 (ENSG00000167207), NLRP7 (ENSG00000167634), 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 14 — Q86W24 (reviewed: Q86W24)

Alternative names: Nucleotide-binding oligomerization domain protein 5

All UniProt accessions (1): Q86W24

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in inflammation and spermatogenesis.

Subcellular location. Cytoplasm.

Tissue specificity. Testis-specific.

Domain organisation. Upon heterologous expression, a small proportion of the isolated Pyrin domain forms homodimers and higher oligomers.

Similarity. Belongs to the NLRP family.

RefSeq proteins (1): NP_789792* (*=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 (42 total): sequence variant 17, repeat 11, helix 7, domain 2, chain 1, region of interest 1, binding site 1, mutagenesis site 1, turn 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
4N1L	X-RAY DIFFRACTION	1.99
4N1J	X-RAY DIFFRACTION	2.6
4N1K	X-RAY DIFFRACTION	3
9LN6	ELECTRON MICROSCOPY	3.49

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86W24-F1	85.47	0.57

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): 183–190

Mutagenesis-validated functional residues (1):

Position	Phenotype
84	increased thermal stability of the pyrin domain.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 46 (showing top): GOBP_INFLAMMATORY_RESPONSE, GOBP_MALE_GAMETE_GENERATION, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_REGULATION_OF_INFLAMMATORY_RESPONSE, GOBP_REGULATION_OF_DEFENSE_RESPONSE, ZHOU_INFLAMMATORY_RESPONSE_LIVE_UP, GOMF_ADENYL_NUCLEOTIDE_BINDING, ZNF8_TARGET_GENES, ZNF92_TARGET_GENES, MIR1285_3P, MIR297, MIR5189_5P, MIR3187_5P

GO Biological Process (3): spermatogenesis (GO:0007283), cell differentiation (GO:0030154), 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
developmental process involved in reproduction	1
male gamete generation	1
cellular developmental process	1
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

474 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NLRP14	CD47	Q08722	840
NLRP14	MEFV	O15553	771
NLRP14	CASP1	P29466	664
NLRP14	TBK1	Q9UHD2	654
NLRP14	THBS1	P07996	570
NLRP14	RIGI	O95786	509
NLRP14	MAVS	Q7Z434	489
NLRP14	PYCARD	Q9ULZ3	450
NLRP14	SIRPA	P78324	393
NLRP14	GRIFIN	A4D1Z8	387
NLRP14	NLRC4	Q9NPP4	370
NLRP14	FKBP3	Q00688	355
NLRP14	PYDC2	Q56P42	310
NLRP14	NAIP	Q13075	309
NLRP14	CD36	P16671	305
NLRP14	OR2D3	Q8NGH3	305

IntAct

4 interactions, top by confidence:

A	B	Type	Score
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350

BioGRID (8): NLRP14 (Co-fractionation), NLRP14 (Affinity Capture-MS), RPL4 (Cross-Linking-MS (XL-MS)), NLRP14 (Cross-Linking-MS (XL-MS)), ALDOA (Cross-Linking-MS (XL-MS)), ALDOC (Cross-Linking-MS (XL-MS)), NLRP14 (Cross-Linking-MS (XL-MS)), NLRP14 (Cross-Linking-MS (XL-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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	265
Likely benign	22
Benign	54

Top pathogenic / likely-pathogenic (0)

SpliceAI

2521 predictions. Top by Δscore:

Variant	Effect	Δscore
11:7038561:CACA:C	acceptor_loss	1.0000
11:7038562:ACAG:A	acceptor_loss	1.0000
11:7038564:A:AG	acceptor_gain	1.0000
11:7038564:AGAG:A	acceptor_gain	1.0000
11:7038565:G:GG	acceptor_gain	1.0000
11:7038565:GA:G	acceptor_gain	1.0000
11:7038565:GAGG:G	acceptor_gain	1.0000
11:7038565:GAGGC:G	acceptor_gain	1.0000
11:7038626:G:A	acceptor_gain	1.0000
11:7038871:CAACT:C	donor_gain	1.0000
11:7038873:ACT:A	donor_gain	1.0000
11:7038874:CT:C	donor_gain	1.0000
11:7038874:CTGT:C	donor_loss	1.0000
11:7038875:TG:T	donor_loss	1.0000
11:7038876:G:GG	donor_gain	1.0000
11:7038877:T:A	donor_loss	1.0000
11:7042368:C:G	acceptor_gain	1.0000
11:7042384:TTAGG:T	acceptor_loss	1.0000
11:7057810:GCCT:G	donor_gain	1.0000
11:7058278:A:AG	acceptor_gain	1.0000
11:7058279:G:GA	acceptor_gain	1.0000
11:7058279:GCTTA:G	acceptor_gain	1.0000
11:7058449:GT:G	donor_gain	1.0000
11:7058451:G:GG	donor_gain	1.0000
11:7059954:C:G	acceptor_gain	1.0000
11:7060062:GGA:G	donor_gain	1.0000
11:7060063:GA:G	donor_gain	1.0000
11:7060063:GAG:G	donor_gain	1.0000
11:7060065:G:GG	donor_gain	1.0000
11:7070282:A:AG	acceptor_gain	1.0000

AlphaMissense

7269 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:7042592:A:T	K189I	0.976
11:7038679:G:C	K31N	0.970
11:7038679:G:T	K31N	0.970
11:7042793:T:C	F256S	0.970
11:7042654:T:C	F210L	0.969
11:7042656:T:A	F210L	0.969
11:7042656:T:G	F210L	0.969
11:7042624:T:A	W200R	0.966
11:7042624:T:C	W200R	0.966
11:7042897:A:C	S291R	0.963
11:7042899:T:A	S291R	0.963
11:7042899:T:G	S291R	0.963
11:7043458:T:C	F478L	0.962
11:7043460:C:A	F478L	0.962
11:7043460:C:G	F478L	0.962
11:7057757:T:C	L791P	0.962
11:7043318:C:A	A431D	0.961
11:7042595:C:T	T190I	0.960
11:7042626:G:C	W200C	0.960
11:7042626:G:T	W200C	0.960
11:7049748:T:C	L734P	0.960
11:7042627:G:C	A201P	0.959
11:7042901:T:C	L292S	0.957
11:7046693:T:A	W662R	0.955
11:7046693:T:C	W662R	0.955
11:7057844:T:C	L820P	0.955
11:7038674:T:C	F30L	0.954
11:7038676:C:A	F30L	0.954
11:7038676:C:G	F30L	0.954
11:7038651:T:C	L22P	0.953

dbSNP variants (sampled 300 via entrez): RS1000092774 (11:7078784 G>A), RS1000097050 (11:7039999 T>A), RS1000101866 (11:7028717 C>T), RS1000131162 (11:7084800 T>A), RS1000164894 (11:7077726 C>G), RS1000281589 (11:7051617 TTTC>T), RS1000368892 (11:7022576 T>C,G), RS1000393297 (11:7061254 G>T), RS1000413866 (11:7028726 A>T), RS1000414216 (11:7085044 T>C), RS1000478532 (11:7067668 A>G), RS1000485197 (11:7045703 A>G), RS1000494370 (11:7067677 C>T), RS1000547569 (11:7063205 A>G), RS1000585261 (11:7045482 A>G)

Disease associations

OMIM: gene MIM:609665 | disease phenotypes: MIM:258150

GenCC curated gene-disease

Mondo (1): spermatogenic failure (MONDO:0004983)

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST010725_20	Malaria	4.000000e-69
GCST010725_33	Malaria	2.000000e-67
GCST010725_51	Malaria	1.000000e-55

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
pirinixic acid	affects binding, decreases expression, increases activity	1
CGP 52608	affects binding, increases reaction	1
Benzo(a)pyrene	increases methylation	1
Lead	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	decreases methylation	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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