NWD2

Summary

NWD2 (NACHT and WD repeat domain containing 2, HGNC:29229) is a protein-coding gene on chromosome 4p14, encoding NACHT and WD repeat domain-containing protein 2 (Q9ULI1).

Predicted to be active in synapse.

Source: NCBI Gene 57495 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 223 total
• MANE Select transcript: NM_001144990

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29229
Approved symbol	NWD2
Name	NACHT and WD repeat domain containing 2
Location	4p14
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000174145
Ensembl biotype	protein_coding
OMIM	620172
Entrez	57495

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000309447

RefSeq mRNA: 1 — MANE Select: NM_001144990 NM_001144990

CCDS: CCDS47040

Canonical transcript exons

ENST00000309447 — 7 exons

Exon	Start	End
ENSE00001209240	37443285	37449463
ENSE00001504652	37438801	37439390
ENSE00001504653	37433876	37434020
ENSE00001504654	37430572	37430775
ENSE00001504655	37356366	37356482
ENSE00001554877	37244743	37245218
ENSE00001559304	37325936	37326024

Expression profiles

Bgee: expression breadth broad, 96 present calls, max score 83.18.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.6434 / max 37.3290, expressed in 107 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
47297	0.2951	72
47298	0.1659	81
47296	0.1355	42
47295	0.0469	33

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	83.18	silver quality
Brodmann (1909) area 46	UBERON:0006483	81.57	gold quality
middle temporal gyrus	UBERON:0002771	77.71	gold quality
cortical plate	UBERON:0005343	75.13	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	73.58	gold quality
superior frontal gyrus	UBERON:0002661	73.04	gold quality
prefrontal cortex	UBERON:0000451	72.86	gold quality
Brodmann (1909) area 23	UBERON:0013554	72.09	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	69.94	gold quality
frontal cortex	UBERON:0001870	69.87	gold quality
postcentral gyrus	UBERON:0002581	68.70	gold quality
neocortex	UBERON:0001950	68.27	gold quality
primary visual cortex	UBERON:0002436	68.03	gold quality
entorhinal cortex	UBERON:0002728	67.87	gold quality
Brodmann (1909) area 9	UBERON:0013540	67.03	gold quality
parietal lobe	UBERON:0001872	66.60	gold quality
cerebral cortex	UBERON:0000956	66.46	gold quality
occipital lobe	UBERON:0002021	64.70	gold quality
right frontal lobe	UBERON:0002810	63.46	gold quality
anterior cingulate cortex	UBERON:0009835	62.17	gold quality
omental fat pad	UBERON:0010414	60.99	gold quality
peritoneum	UBERON:0002358	60.93	gold quality
pancreatic ductal cell	CL:0002079	60.91	silver quality
adipose tissue of abdominal region	UBERON:0007808	60.39	gold quality
ganglionic eminence	UBERON:0004023	60.23	gold quality
tibialis anterior	UBERON:0001385	59.97	silver quality
temporal lobe	UBERON:0001871	58.49	gold quality
Ammon’s horn	UBERON:0001954	57.20	gold quality
hypothalamus	UBERON:0001898	55.47	gold quality
epithelial cell of pancreas	CL:0000083	54.76	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.57

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

168 targeting NWD2, 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-4262	100.00	73.26	3931
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-433-3P	99.98	69.37	1203
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-507	99.97	70.11	1915
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-3912-5P	99.95	66.11	925

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nwd2	ENSDARG00000077162
mus_musculus	Nwd2	ENSMUSG00000090061
rattus_norvegicus	Nwd2	ENSRNOG00000051837
drosophila_melanogaster	CG5114	FBGN0036460
caenorhabditis_elegans		WBGENE00013735

Paralogs (1): AAMP (ENSG00000127837)

Protein

Protein identifiers

NACHT and WD repeat domain-containing protein 2 — Q9ULI1 (reviewed: Q9ULI1)

Alternative names: Leucine-rich repeat and WD repeat-containing protein KIAA1239

All UniProt accessions (1): Q9ULI1

RefSeq proteins (1): NP_001138462* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR052752	NACHT-WD_repeat	Family
IPR056534	Beta-prop_NWD2_C	Domain
IPR057588	NWD1/2-like_WH	Domain

Pfam: PF23586, PF25469

UniProt features (19 total): repeat 16, chain 1, sequence variant 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9ULI1-F1	79.63	0.20

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 68 (showing top): GOCC_SYNAPSE, PEDRIOLI_MIR31_TARGETS_UP, CAHOY_NEURONAL, IRF5_TARGET_GENES, MIR548AJ_3P_MIR548X_3P, MIR3646, MIR520D_5P, MIR524_5P, MIR4262, MIR548AW, MIR3680_3P, MIR181A_5P_MIR181B_5P, MIR181D_5P, MIR181C_5P, MIR450B_5P

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (1): synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
cell junction	1

Protein interactions and networks

STRING

2206 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NWD2	WDR93	Q6P2C0	528
NWD2	FAM171B	Q6P995	492
NWD2	SACS	Q9NZJ4	478
NWD2	PLAGL2	Q9UPG8	453
NWD2	MCC	P23508	444
NWD2	SPMIP2	Q96LM5	434
NWD2	TEPSIN	Q96N21	430
NWD2	SCML4	Q8N228	428
NWD2	PTCHD1	Q96NR3	422
NWD2	DMTN	Q08495	418
NWD2	APBB1IP	Q7Z5R6	415
NWD2	ARHGAP12	Q8IWW6	403
NWD2	PXYLP1	Q8TE99	402
NWD2	SNX33	Q8WV41	399
NWD2	DEPDC4	Q8N2C3	393

IntAct

0 interactions, top by confidence:

BioGRID (4): NWD2 (Affinity Capture-MS), NWD2 (Proximity Label-MS), NWD2 (Affinity Capture-RNA), NWD2 (Affinity Capture-MS)

ESM2 similar proteins: A0JMU5, A1A4L5, A2AV36, A2Y8B9, B0X4N1, B3DLB3, B3M1E1, B3MF31, B3P4N5, B4GZ20, B4HJC0, B4I8G2, B4JXV2, B4KA23, B4LVS8, B4NKI9, B4P925, B4PVH6, B4QI55, B4QVW6, B6DMK2, D9IVE5, O14727, O60678, O70467, O88879, Q0V9P1, Q16NS8, Q29B63, Q3EBC8, Q3U213, Q3U3W5, Q4SBY6, Q5RAY7, Q5ZIB9, Q6P2P2, Q6P5U7, Q6PCI6, Q7QIL2, Q80VJ4

Diamond homologs: Q6P5U7, Q9ULI1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	208
Likely benign	11
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1922 predictions. Top by Δscore:

Variant	Effect	Δscore
4:37325929:A:AG	acceptor_gain	1.0000
4:37325930:C:G	acceptor_gain	1.0000
4:37325932:ACAGA:A	acceptor_loss	1.0000
4:37325933:CAGAT:C	acceptor_loss	1.0000
4:37325934:A:AG	acceptor_gain	1.0000
4:37325935:G:GA	acceptor_gain	1.0000
4:37325935:GAT:G	acceptor_gain	1.0000
4:37326020:TTCAG:T	donor_loss	1.0000
4:37326021:TCAG:T	donor_loss	1.0000
4:37326022:CAGG:C	donor_loss	1.0000
4:37326023:AG:A	donor_loss	1.0000
4:37326024:GG:G	donor_loss	1.0000
4:37326025:GTA:G	donor_loss	1.0000
4:37326026:T:A	donor_loss	1.0000
4:37356480:GTT:G	donor_gain	1.0000
4:37356483:G:GG	donor_gain	1.0000
4:37430568:A:AG	acceptor_gain	1.0000
4:37430568:ACAG:A	acceptor_gain	1.0000
4:37430568:ACAGG:A	acceptor_gain	1.0000
4:37430569:C:G	acceptor_gain	1.0000
4:37430569:CA:C	acceptor_loss	1.0000
4:37430570:A:AG	acceptor_gain	1.0000
4:37430570:A:AT	acceptor_loss	1.0000
4:37430570:AG:A	acceptor_gain	1.0000
4:37430570:AGG:A	acceptor_gain	1.0000
4:37430571:G:GA	acceptor_gain	1.0000
4:37430571:GG:G	acceptor_gain	1.0000
4:37430571:GGG:G	acceptor_gain	1.0000
4:37430705:A:G	donor_gain	1.0000
4:37430755:C:G	donor_gain	1.0000

AlphaMissense

11519 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:37438876:G:T	R261M	1.000
4:37444182:T:A	W732R	1.000
4:37444182:T:C	W732R	1.000
4:37444729:T:C	L914P	1.000
4:37245189:T:A	V41D	0.999
4:37245195:T:A	V43D	0.999
4:37325984:T:C	L67P	0.999
4:37325995:T:C	C71R	0.999
4:37325997:C:G	C71W	0.999
4:37356469:G:A	G115D	0.999
4:37356481:T:A	V119D	0.999
4:37430572:G:A	G120R	0.999
4:37430572:G:C	G120R	0.999
4:37430573:G:A	G120E	0.999
4:37430712:C:A	N166K	0.999
4:37430712:C:G	N166K	0.999
4:37438825:C:A	A244D	0.999
4:37438866:T:C	C258R	0.999
4:37438869:T:G	Y259D	0.999
4:37438876:G:C	R261T	0.999
4:37438877:G:C	R261S	0.999
4:37438877:G:T	R261S	0.999
4:37443576:T:A	W530R	0.999
4:37443576:T:C	W530R	0.999
4:37443758:G:C	R590S	0.999
4:37443758:G:T	R590S	0.999
4:37443776:G:C	Q596H	0.999
4:37443776:G:T	Q596H	0.999
4:37443855:T:A	W623R	0.999
4:37443855:T:C	W623R	0.999

dbSNP variants (sampled 300 via entrez): RS1000003249 (4:37432176 T>C), RS1000029480 (4:37447358 T>C), RS1000046728 (4:37353663 G>A,C), RS1000052435 (4:37314462 T>G), RS1000099230 (4:37440260 A>G), RS1000107958 (4:37320213 G>A,T), RS1000115366 (4:37265629 C>T), RS1000128839 (4:37346896 G>A,T), RS10001618 (4:37339049 T>C,G), RS1000166436 (4:37267123 A>T), RS1000176847 (4:37282656 A>T), RS10001922 (4:37324306 C>T), RS1000199127 (4:37334620 C>A,T), RS10001995 (4:37315571 A>C,G), RS1000204893 (4:37344112 T>C)

Disease associations

OMIM: gene MIM:620172 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST003654_7	Bone mineral density (Ward’s triangle area)	3.000000e-06
GCST007743_13	Iris color (L* coordinate)	5.000000e-06
GCST010242_397	HDL cholesterol levels	6.000000e-10
GCST010724_7	HOMA-B (corrected for HOMA-IR)	2.000000e-07
GCST011177_2	Lung adenocarcinoma (survival time) in never smokers	7.000000e-07
GCST012276_12	Clostridioides difficle infection in antibiotics-users	5.000000e-06
GCST012277_22	Clostridioides difficle infection	4.000000e-06
GCST90013406_261	Liver enzyme levels (alkaline phosphatase)	1.000000e-16

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0007785	femoral neck bone mineral density
EFO:0009764	eye colour measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004469	HOMA-B
EFO:0000714	survival time
EFO:0009130	clostridium difficile infection
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	5
entinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
trichostatin A	increases expression	1
sodium arsenite	decreases expression	1
hydroquinone	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
15-acetyldeoxynivalenol	increases expression	1
avobenzone	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
belinostat	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
1,8-dinitro-4,5-dihydroxyanthraquinone	affects response to substance	1
Benzo(a)pyrene	decreases methylation, affects methylation	1
Caffeine	increases phosphorylation	1
Lipopolysaccharides	affects response to substance, increases expression	1
Rotenone	increases expression	1
Tobacco Smoke Pollution	increases expression	1

Clinical trials (associated diseases)

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