NHLRC4

Summary

NHLRC4 (NHL repeat containing 4, HGNC:26700) is a protein-coding gene on chromosome 16p13.3, encoding NHL-repeat-containing protein 4 (P0CG21).

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 14 total
• MANE Select transcript: NM_001301159

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26700
Approved symbol	NHLRC4
Name	NHL repeat containing 4
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000257108
Ensembl biotype	protein_coding
Entrez	283948

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000424439, ENST00000540585

RefSeq mRNA: 2 — MANE Select: NM_001301159 NM_001301159, NM_176677

CCDS: CCDS45366

Canonical transcript exons

ENST00000424439 — 2 exons

Exon	Start	End
ENSE00001786059	567471	569495
ENSE00002268467	567005	567075

Expression profiles

Bgee: expression breadth ubiquitous, 146 present calls, max score 92.50.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0475 / max 15.0808, expressed in 11 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
151944	0.9811	437
151945	0.0475	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	92.50	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	80.11	gold quality
right adrenal gland cortex	UBERON:0035827	74.41	gold quality
right adrenal gland	UBERON:0001233	73.98	gold quality
left adrenal gland	UBERON:0001234	73.34	gold quality
mucosa of paranasal sinus	UBERON:0005030	73.29	gold quality
nasal cavity epithelium	UBERON:0005384	73.22	gold quality
left adrenal gland cortex	UBERON:0035825	73.22	gold quality
trabecular bone tissue	UBERON:0002483	72.85	gold quality
adrenal cortex	UBERON:0001235	72.45	gold quality
adult mammalian kidney	UBERON:0000082	72.36	gold quality
bronchial epithelial cell	CL:0002328	71.65	gold quality
bronchus	UBERON:0002185	71.11	gold quality
adrenal gland	UBERON:0002369	70.41	gold quality
oocyte	CL:0000023	70.30	gold quality
nasal cavity mucosa	UBERON:0001826	69.44	gold quality
esophagus squamous epithelium	UBERON:0006920	69.33	gold quality
biceps brachii	UBERON:0001507	68.63	gold quality
bone marrow	UBERON:0002371	68.63	gold quality
mammary duct	UBERON:0001765	68.17	gold quality
stromal cell of endometrium	CL:0002255	67.86	gold quality
spleen	UBERON:0002106	67.70	gold quality
apex of heart	UBERON:0002098	67.59	gold quality
fallopian tube	UBERON:0003889	67.57	gold quality
metanephros	UBERON:0000081	67.26	gold quality
kidney	UBERON:0002113	67.16	gold quality
metanephros cortex	UBERON:0010533	66.40	gold quality
secondary oocyte	CL:0000655	66.35	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	66.22	gold quality
right ovary	UBERON:0002118	65.62	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.54

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

32 targeting NHLRC4, 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-6845-3P	99.94	66.88	1439
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-3191-3P	99.45	63.94	356
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-6885-5P	98.71	64.33	902
HSA-MIR-6810-5P	98.29	66.21	975
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-3144-5P	97.64	65.45	646
HSA-MIR-1226-3P	97.51	66.32	1063
HSA-MIR-4286	97.20	64.37	1587
HSA-MIR-4288	97.11	67.23	1636

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Nhlrc4	ENSMUSG00000090113
rattus_norvegicus		ENSRNOG00000067173

Paralogs (2): ZNF750 (ENSG00000141579), PRR35 (ENSG00000161992)

Protein

Protein identifiers

NHL-repeat-containing protein 4 — P0CG21 (reviewed: P0CG21)

All UniProt accessions (1): P0CG21

RefSeq proteins (2): NP_001288088, NP_788850 (=MANE)

Domains & families (InterPro)

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

Pfam: PF01436

UniProt features (3 total): repeat 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0CG21-F1	94.00	0.82

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 20 (showing top): NIKOLSKY_BREAST_CANCER_16P13_AMPLICON, ZNF577_TARGET_GENES, ZNF768_TARGET_GENES, MIR6810_5P, GAO_ESOPHAGUS_25W_C1_CILIATED_EPITHELIAL_CELLS, DESCARTES_MAIN_FETAL_CILIATED_EPITHELIAL_CELLS, DESCARTES_FETAL_INTESTINE_ERYTHROBLASTS, DESCARTES_FETAL_LUNG_CILIATED_EPITHELIAL_CELLS, NFXL1_TARGET_GENES, HARALAMBIEVA_PBMC_FLUARIX_AGE_50_74YO_CORR_WITH_28D_MEM_B_CELL_RESPONSE_AT_3DY_NEGATIVE, TRAVAGLINI_LUNG_CILIATED_CELL, TRAVAGLINI_LUNG_PROXIMAL_CILIATED_CELL, GSE17974_IL4_AND_ANTI_IL12_VS_UNTREATED_1H_ACT_CD4_TCELL_DN, GSE14413_UNSTIM_VS_IFNB_STIM_RAW264_CELLS_DN, GSE13887_ACT_CD4_VS_NO_TREATED_CD4_TCELL_DN

GO Biological Process (0):

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

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1

Protein interactions and networks

STRING

114 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NHLRC4	KCNJ5-AS1	Q8TAV5	542
NHLRC4	CIMAP1D	Q3SX64	507
NHLRC4	ZKSCAN2	Q63HK3	399
NHLRC4	KIF9	Q9HAQ2	394
NHLRC4	OR2B11	Q5JQS5	299
NHLRC4	ACOT7	O00154	287
NHLRC4	WDR25	Q64LD2	269
NHLRC4	KLC3	Q6P597	259
NHLRC4	PPP1R13L	Q8WUF5	248
NHLRC4	KIF7	Q2M1P5	248
NHLRC4	PRRC1	Q96M27	246
NHLRC4	KLHL8	Q9P2G9	245
NHLRC4	ZNF862	O60290	244
NHLRC4	LCN6	P62502	224
NHLRC4	PCSK6	P29122	222

IntAct

63 interactions, top by confidence:

A	B	Type	Score
TLX3	NHLRC4	psi-mi:“MI:0915”(physical association)	0.560
IGFN1	NHLRC4	psi-mi:“MI:0915”(physical association)	0.560
DTX2	NHLRC4	psi-mi:“MI:0915”(physical association)	0.560
PRKAB2	NHLRC4	psi-mi:“MI:0915”(physical association)	0.560
NHLRC4	PITX1	psi-mi:“MI:0915”(physical association)	0.560
NHLRC4	CERK	psi-mi:“MI:0915”(physical association)	0.560
NHLRC4	DMRT3	psi-mi:“MI:0915”(physical association)	0.560
NHLRC4	KRTAP13-2	psi-mi:“MI:0915”(physical association)	0.560
NHLRC4	HSF4	psi-mi:“MI:0915”(physical association)	0.560
	NHLRC4	psi-mi:“MI:0915”(physical association)	0.560
NHLRC4	POU4F3	psi-mi:“MI:0915”(physical association)	0.560
NHLRC4	SPAG8	psi-mi:“MI:0915”(physical association)	0.560
NHLRC4	OTX1	psi-mi:“MI:0915”(physical association)	0.560
POGZ	NHLRC4	psi-mi:“MI:0915”(physical association)	0.560
NHLRC4	KRTAP15-1	psi-mi:“MI:0915”(physical association)	0.560
NHLRC4	PATZ1	psi-mi:“MI:0915”(physical association)	0.560
NHLRC4	IGFN1	psi-mi:“MI:0915”(physical association)	0.560
NHLRC4	DTX2	psi-mi:“MI:0915”(physical association)	0.560
NHLRC4	MYLIP	psi-mi:“MI:0915”(physical association)	0.560
NHLRC4	KRTAP26-1	psi-mi:“MI:0915”(physical association)	0.560
NHLRC4	ENKD1	psi-mi:“MI:0915”(physical association)	0.560
NHLRC4	DDIT4L	psi-mi:“MI:0915”(physical association)	0.560
SPAG8	NHLRC4	psi-mi:“MI:0915”(physical association)	0.000
OTX1	NHLRC4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (20): NHLRC4 (Two-hybrid), NHLRC4 (Two-hybrid), NHLRC4 (Two-hybrid), NHLRC4 (Two-hybrid), NHLRC4 (Two-hybrid), NHLRC4 (Two-hybrid), NHLRC4 (Two-hybrid), NHLRC4 (Two-hybrid), NHLRC4 (Two-hybrid), NHLRC4 (Two-hybrid), NHLRC4 (Two-hybrid), NHLRC4 (Two-hybrid), NHLRC4 (Two-hybrid), NHLRC4 (Two-hybrid), NHLRC4 (Two-hybrid)

ESM2 similar proteins: A6QP75, D3YWP0, O95294, P0CG21, P57737, P57775, Q0D2K2, Q0V8F1, Q2TBI8, Q3SZD4, Q3T0A0, Q3UP44, Q4FZD7, Q58D06, Q5E9V4, Q5H879, Q5RBW3, Q60I27, Q63148, Q6AYG0, Q6IMG5, Q6Q7D1, Q6RFH5, Q6VVB1, Q86UR1, Q86VU5, Q8BIG7, Q8BR37, Q8C3F7, Q8K1S1, Q8N135, Q8N9H8, Q8NEP7, Q8TCX5, Q8VCG3, Q8VHS5, Q8WWP7, Q8WXI3, Q91ZT7, Q969S8

Diamond homologs: P0CG21, Q13049, Q3UP44, Q8CH72, A5D8S5, D2H6Z0, D2H788, D3ZBM4, D4A723, E1C2W7, M0QZC1, O60858, Q11072, Q32L60, Q4VGL6, Q58EC8, Q5M7V1, Q5TC82, Q68EV7, Q6GND7, Q6IMG5, Q6INB3, Q6NUC6, Q6VVB1, Q810I1, Q810I2, Q865W2, Q86UV6, Q86UV7, Q86XT4, Q8BG47, Q8C432, Q8N6D2, Q8N8N0, Q9CYB0, O54952

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	9
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

173 predictions. Top by Δscore:

Variant	Effect	Δscore
16:567076:G:C	donor_loss	1.0000
16:567076:GTAA:G	donor_loss	1.0000
16:567077:T:G	donor_loss	1.0000
16:567076:G:GG	donor_gain	0.9900
16:567494:A:AG	acceptor_gain	0.9900
16:567495:G:GG	acceptor_gain	0.9900
16:567495:GCCC:G	acceptor_gain	0.9800
16:567495:GC:G	acceptor_gain	0.9700
16:567495:GCCCC:G	acceptor_gain	0.9700
16:567491:T:A	acceptor_gain	0.9600
16:567492:GCAGC:G	acceptor_loss	0.9600
16:567493:CA:C	acceptor_loss	0.9600
16:567495:G:GC	acceptor_loss	0.9600
16:567495:GCC:G	acceptor_gain	0.9400
16:567071:CCCAG:C	donor_gain	0.9200
16:567074:AG:A	donor_gain	0.9200
16:567075:GG:G	donor_gain	0.9200
16:567491:TGCAG:T	acceptor_gain	0.9200
16:567495:G:T	acceptor_gain	0.9000
16:567073:CAG:C	donor_gain	0.8900
16:567493:CAG:C	acceptor_gain	0.8900
16:567492:GCAG:G	acceptor_gain	0.8800
16:567494:A:T	acceptor_gain	0.8800
16:567840:G:GA	donor_gain	0.8800
16:567490:TTGCA:T	acceptor_gain	0.8700
16:567072:CCAG:C	donor_gain	0.8600
16:567494:A:AT	acceptor_loss	0.8600
16:567495:G:GA	acceptor_loss	0.8600
16:567843:C:A	donor_gain	0.8400
16:567632:G:GA	donor_gain	0.8300

AlphaMissense

777 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:568270:T:C	F75L	0.955
16:568272:T:A	F75L	0.955
16:568272:T:G	F75L	0.955
16:568271:T:C	F75S	0.950
16:568385:T:A	I113N	0.950
16:568235:T:A	I63N	0.947
16:568108:A:C	S21R	0.946
16:568110:T:A	S21R	0.946
16:568110:T:G	S21R	0.946
16:568238:T:A	V64E	0.941
16:568135:T:C	F30L	0.931
16:568137:T:A	F30L	0.931
16:568137:T:G	F30L	0.931
16:568322:C:A	P92H	0.931
16:568333:G:C	A96P	0.930
16:568189:T:C	F48L	0.927
16:568191:C:A	F48L	0.927
16:568191:C:G	F48L	0.927
16:568262:T:A	V72E	0.925
16:568389:G:C	K114N	0.925
16:568389:G:T	K114N	0.925
16:568385:T:G	I113S	0.923
16:568381:T:C	S112P	0.918
16:568243:G:C	D66H	0.913
16:568385:T:C	I113T	0.912
16:568366:G:C	D107H	0.909
16:568393:T:G	Y116D	0.908
16:568243:G:T	D66Y	0.905
16:568271:T:G	F75C	0.904
16:568361:T:A	V105E	0.903

dbSNP variants (sampled 300 via entrez): RS1000990691 (16:566300 G>T), RS1001419601 (16:566922 C>T), RS1001772200 (16:566748 G>A), RS1002368237 (16:565852 C>T), RS1002422093 (16:566060 G>A,C), RS1002819826 (16:569848 G>T), RS1003071533 (16:569406 C>T), RS1003533637 (16:568943 G>C), RS1004121274 (16:567964 C>T), RS1004352454 (16:568343 C>A), RS1005039109 (16:568616 C>A), RS1005635783 (16:567668 G>A), RS1006334295 (16:566547 T>C), RS1006841966 (16:567375 C>A), RS1006855414 (16:566628 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

1 associations (top):

Study	Trait	p-value
GCST004605_15	Mean corpuscular hemoglobin concentration	2.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004528	mean corpuscular hemoglobin concentration

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
dicrotophos	decreases expression	1
ferrous chloride	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
enniatins	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression, affects cotreatment	1
Smoke	increases expression, increases abundance	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
Cyclosporine	decreases methylation	1

Clinical trials (associated diseases)

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