NHLRC3

Summary

NHLRC3 (NHL repeat containing 3, HGNC:33751) is a protein-coding gene on chromosome 13q13.3, encoding NHL repeat-containing protein 3 (Q5JS37).

This gene encodes a protein containing NCL-1, HT2A and Lin-41 (NHL) family repeats. Mammalian NHL-repeat containing proteins may be involved in a variety of enzymatic processes, including protein modification through ubiquitination. Alternatively spliced transcript variants have been observed for this gene.

Source: NCBI Gene 387921 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 62 total
• MANE Select transcript: NM_001012754

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33751
Approved symbol	NHLRC3
Name	NHL repeat containing 3
Location	13q13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000188811
Ensembl biotype	protein_coding
Entrez	387921

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 retained_intron

ENST00000379599, ENST00000379600, ENST00000470258, ENST00000473371, ENST00000485407

RefSeq mRNA: 2 — MANE Select: NM_001012754 NM_001012754, NM_001017370

CCDS: CCDS31961, CCDS31962

Canonical transcript exons

ENST00000379600 — 7 exons

Exon	Start	End
ENSE00001367043	39047674	39050109
ENSE00001375443	39047040	39047152
ENSE00003315621	39038456	39038723
ENSE00003459606	39039136	39039288
ENSE00003552089	39042105	39042305
ENSE00003652368	39044090	39044181
ENSE00003693968	39039564	39039711

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 97.69.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.6479 / max 100.5946, expressed in 1774 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
134810	11.6272	1755
134809	1.7655	858
134811	1.0302	473
207011	0.2251	97

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	97.69	gold quality
secondary oocyte	CL:0000655	95.90	gold quality
oviduct epithelium	UBERON:0004804	93.50	gold quality
calcaneal tendon	UBERON:0003701	93.13	gold quality
germinal epithelium of ovary	UBERON:0001304	92.72	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.22	gold quality
adrenal tissue	UBERON:0018303	91.92	gold quality
tibia	UBERON:0000979	91.65	gold quality
rectum	UBERON:0001052	91.54	gold quality
monocyte	CL:0000576	91.22	gold quality
body of pancreas	UBERON:0001150	91.22	gold quality
leukocyte	CL:0000738	90.57	gold quality
subcutaneous adipose tissue	UBERON:0002190	90.57	gold quality
epithelial cell of pancreas	CL:0000083	90.54	gold quality
cardiac muscle of right atrium	UBERON:0003379	90.35	gold quality
left lobe of thyroid gland	UBERON:0001120	90.33	gold quality
thyroid gland	UBERON:0002046	90.29	gold quality
right lobe of thyroid gland	UBERON:0001119	90.24	gold quality
endometrium	UBERON:0001295	90.23	gold quality
cauda epididymis	UBERON:0004360	90.23	gold quality
left ovary	UBERON:0002119	90.18	gold quality
adipose tissue	UBERON:0001013	90.17	gold quality
right ovary	UBERON:0002118	90.12	gold quality
right uterine tube	UBERON:0001302	90.11	gold quality
ovary	UBERON:0000992	89.71	gold quality
decidua	UBERON:0002450	89.65	gold quality
minor salivary gland	UBERON:0001830	89.40	gold quality
parietal pleura	UBERON:0002400	89.38	gold quality
tendon	UBERON:0000043	89.37	gold quality
smooth muscle tissue	UBERON:0001135	89.22	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.49

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

136 targeting NHLRC3, 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-3163	100.00	77.23	8605
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4500	99.99	72.72	2367
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	NHLRC3	ENSDARG00000102127
mus_musculus	Nhlrc3	ENSMUSG00000042997
rattus_norvegicus	Nhlrc3	ENSRNOG00000010843

Protein

Protein identifiers

NHL repeat-containing protein 3 — Q5JS37 (reviewed: Q5JS37)

All UniProt accessions (2): C9J973, Q5JS37

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5JS37-1	1	yes
Q5JS37-2	2

RefSeq proteins (2): NP_001012772, NP_001017370 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001258	NHL_repeat	Repeat
IPR011042	6-blade_b-propeller_TolB-like	Homologous_superfamily

Pfam: PF01436

UniProt features (12 total): repeat 4, glycosylation site 4, signal peptide 1, chain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5JS37-F1	89.31	0.83

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (4): 32, 101, 206, 278

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 150 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, chr13q13, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_PROTEIN_POLYUBIQUITINATION, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, MILI_PSEUDOPODIA_CHEMOTAXIS_DN, GOBP_PROTEIN_CATABOLIC_PROCESS, GOCC_SECRETORY_VESICLE, GOCC_VESICLE_LUMEN, GOCC_VACUOLAR_LUMEN, GOBP_PROTEOLYSIS, KRIGE_RESPONSE_TO_TOSEDOSTAT_24HR_UP

GO Biological Process (2): protein polyubiquitination (GO:0000209), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161)

GO Molecular Function (2): ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515)

GO Cellular Component (2): extracellular region (GO:0005576), azurophil granule lumen (GO:0035578)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein ubiquitination	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
cellular anatomical structure	1
vacuolar lumen	1
secretory granule lumen	1
azurophil granule	1

Protein interactions and networks

STRING

364 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NHLRC3	PROSER1	Q86XN7	664
NHLRC3	PRR14L	Q5THK1	662
NHLRC3	PPIP5K2	O43314	573
NHLRC3	ZDHHC21	Q8IVQ6	570
NHLRC3	KYAT1	Q16773	507
NHLRC3	PNPO	Q9NVS9	507
NHLRC3	STOML3	Q8TAV4	403
NHLRC3	YIPF3	Q9GZM5	400
NHLRC3	CCDC169	A6NNP5	400
NHLRC3	VASN	Q6EMK4	392
NHLRC3	PTPRB	P23467	376
NHLRC3	WFDC3	Q8IUB2	367
NHLRC3	CD300LG	Q6UXG3	365
NHLRC3	FREM2	Q5SZK8	364
NHLRC3	C1orf198	Q9H425	357

IntAct

13 interactions, top by confidence:

A	B	Type	Score
AGRP	TK1	psi-mi:“MI:0914”(association)	0.640
SCGB1D1	FAM234B	psi-mi:“MI:0914”(association)	0.530
DEFB121	COL6A2	psi-mi:“MI:0914”(association)	0.530
GALNS	CLGN	psi-mi:“MI:0914”(association)	0.530
CANX	HLA-A	psi-mi:“MI:0914”(association)	0.350
DDOST	ATL3	psi-mi:“MI:0914”(association)	0.350
NHLRC3	OGG1	psi-mi:“MI:0914”(association)	0.350
NHLRC3	CLGN	psi-mi:“MI:0914”(association)	0.350
MAGT1	PES1	psi-mi:“MI:0914”(association)	0.350
SLC44A1	UPK3BL1	psi-mi:“MI:0914”(association)	0.350

BioGRID (45): NHLRC3 (Affinity Capture-MS), NHLRC3 (Affinity Capture-MS), NHLRC3 (Affinity Capture-MS), NHLRC3 (Affinity Capture-MS), NHLRC3 (Affinity Capture-MS), NHLRC3 (Affinity Capture-MS), NHLRC3 (Affinity Capture-MS), NHLRC3 (Affinity Capture-MS), NHLRC3 (Affinity Capture-MS), NHLRC3 (Affinity Capture-MS), NHLRC3 (Affinity Capture-MS), NHLRC3 (Proximity Label-MS), NHLRC3 (Proximity Label-MS), SLC19A1 (Affinity Capture-MS), NHLRC3 (Affinity Capture-MS)

ESM2 similar proteins: A0A084B9Z4, A0A0A2JQ23, A0A0A7LRQ7, A0A142I728, A0A2U8U2M1, A0A345BJP5, A0A3G1DJI3, A0A4P8GEA3, A0A8J9S8U9, A0A8R9YVA6, A1DD80, A2R3X3, A5ABH0, B8NGU1, C5PIJ9, C7YS44, D4AJ87, D4AR77, D4AV38, D4AZY1, D4D7X4, E1ACQ5, G0KYA7, L7WU85, O01811, O42814, P35903, P46057, P84193, Q01940, Q0CVX4, Q0D1P8, Q0UI13, Q17043, Q2TXF4, Q2TXF9, Q2UDJ8, Q5B5P1, Q5BA89, Q5JS37

Diamond homologs: O01404, P08478, P10731, P12890, P14925, P19021, P83388, P91268, P97467, Q5JS37, Q5R9V0, Q95XM2, Q9V5E1, Q13049, Q8CCH2, Q8CH72, Q9U489

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	45
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1247 predictions. Top by Δscore:

Variant	Effect	Δscore
13:39038426:G:GT	donor_gain	1.0000
13:39039284:GTCAA:G	donor_gain	1.0000
13:39039285:TCAAG:T	donor_loss	1.0000
13:39039286:CAAGT:C	donor_loss	1.0000
13:39039287:AAGT:A	donor_loss	1.0000
13:39039288:AGT:A	donor_loss	1.0000
13:39039289:G:GG	donor_gain	1.0000
13:39039289:GTAA:G	donor_loss	1.0000
13:39039290:T:G	donor_loss	1.0000
13:39039561:CAGAG:C	acceptor_gain	1.0000
13:39039562:AGAGA:A	acceptor_gain	1.0000
13:39039563:GA:G	acceptor_gain	1.0000
13:39039563:GAGAG:G	acceptor_gain	1.0000
13:39039706:G:GT	donor_gain	1.0000
13:39039709:GTG:G	donor_gain	1.0000
13:39039709:GTGGT:G	donor_loss	1.0000
13:39039711:GGTA:G	donor_loss	1.0000
13:39039712:G:GG	donor_gain	1.0000
13:39039713:TATG:T	donor_loss	1.0000
13:39047028:T:TA	acceptor_gain	1.0000
13:39047030:T:TA	acceptor_gain	1.0000
13:39047036:TCA:T	acceptor_loss	1.0000
13:39047037:CA:C	acceptor_loss	1.0000
13:39047038:A:AC	acceptor_loss	1.0000
13:39047038:A:AG	acceptor_gain	1.0000
13:39047038:AGGT:A	acceptor_gain	1.0000
13:39047039:G:C	acceptor_loss	1.0000
13:39047039:G:GA	acceptor_gain	1.0000
13:39047039:GGT:G	acceptor_gain	1.0000
13:39047039:GGTG:G	acceptor_gain	1.0000

AlphaMissense

2254 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:39039205:T:A	W52R	0.996
13:39039205:T:C	W52R	0.996
13:39047043:T:A	W228R	0.992
13:39047043:T:C	W228R	0.992
13:39039207:G:C	W52C	0.991
13:39039207:G:T	W52C	0.991
13:39042123:T:A	V135D	0.990
13:39042260:G:C	D181H	0.990
13:39044155:A:C	S218R	0.990
13:39044157:T:A	S218R	0.990
13:39044157:T:G	S218R	0.990
13:39047047:T:A	V229D	0.990
13:39042131:T:G	Y138D	0.989
13:39044159:T:A	V219D	0.989
13:39039690:T:A	W122R	0.988
13:39039690:T:C	W122R	0.988
13:39039699:G:C	D125H	0.988
13:39042127:A:C	K136N	0.986
13:39042127:A:T	K136N	0.986
13:39044141:T:C	F213S	0.986
13:39044150:C:A	P216H	0.986
13:39047052:G:C	D231H	0.986
13:39042297:T:C	L193P	0.985
13:39039699:G:T	D125Y	0.984
13:39042260:G:T	D181Y	0.982
13:39047056:G:C	R232P	0.982
13:39042264:G:A	G182E	0.981
13:39039250:G:C	A67P	0.980
13:39039648:C:G	H108D	0.980
13:39042207:T:C	F163S	0.980

dbSNP variants (sampled 300 via entrez): RS1000004272 (13:39045101 G>C), RS1000124985 (13:39042549 A>G), RS1000248347 (13:39048630 C>T), RS1001655427 (13:39040398 A>G), RS1001681059 (13:39046396 T>A), RS1001712335 (13:39046728 C>A,T), RS1001881201 (13:39042162 T>G), RS1002177360 (13:39041647 T>C), RS1002250185 (13:39041866 G>A), RS1002364254 (13:39036450 C>G), RS1002766657 (13:39037676 G>A), RS1002858203 (13:39040053 T>G), RS1002917936 (13:39040200 AAAAAG>A), RS1002952768 (13:39046326 A>T), RS1003286650 (13:39044962 A>G)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003518_90	Daytime sleep phenotypes	5.000000e-06
GCST007511_14	Alzheimer’s disease (late onset)	4.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007828	daytime rest measurement
EFO:1001870	late-onset Alzheimers disease

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

41 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression	2
Cisplatin	affects expression, affects cotreatment, increases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	decreases expression	2
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression, affects cotreatment	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
N-acetyl-4-benzoquinoneimine	affects response to substance	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
monomethylarsonous acid	decreases expression	1
abrine	decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases expression, increases response to substance	1
bisphenol S	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Decitabine	affects expression	1
Fulvestrant	increases methylation	1
Leflunomide	decreases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Indomethacin	increases expression, affects cotreatment	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression	1

Clinical trials (associated diseases)

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