NOXRED1

Summary

NOXRED1 (NADP dependent oxidoreductase domain containing 1, HGNC:20487) is a protein-coding gene on chromosome 14q24.3, encoding NADP-dependent oxidoreductase domain-containing protein 1 (Q6NXP6). Probable oxidoreductase.

Predicted to enable pyrroline-5-carboxylate reductase activity. Predicted to be involved in L-proline biosynthetic process.

Source: NCBI Gene 122945 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 67 total
• MANE Select transcript: NM_001113475

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20487
Approved symbol	NOXRED1
Name	NADP dependent oxidoreductase domain containing 1
Location	14q24.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ32809
Ensembl gene	ENSG00000165555
Ensembl biotype	protein_coding
Entrez	122945

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 retained_intron

ENST00000380835, ENST00000555603, ENST00000555901

RefSeq mRNA: 2 — MANE Select: NM_001113475 NM_001113475, NM_001394980

CCDS: CCDS45142

Canonical transcript exons

ENST00000380835 — 6 exons

Exon	Start	End
ENSE00001486463	77394021	77394805
ENSE00001486466	77405913	77406135
ENSE00001486470	77406724	77406875
ENSE00003555073	77422735	77423523
ENSE00003595519	77407465	77407645
ENSE00003669317	77413934	77414127

Expression profiles

Bgee: expression breadth ubiquitous, 156 present calls, max score 84.37.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0066 / max 4.9619, expressed in 3 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
144227	0.0066	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.37	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.65	gold quality
sperm	CL:0000019	79.95	silver quality
left testis	UBERON:0004533	76.78	gold quality
right testis	UBERON:0004534	75.03	gold quality
testis	UBERON:0000473	74.23	gold quality
pancreatic ductal cell	CL:0002079	70.54	silver quality
right uterine tube	UBERON:0001302	67.94	gold quality
tibialis anterior	UBERON:0001385	67.64	silver quality
ventricular zone	UBERON:0003053	63.38	gold quality
ileal mucosa	UBERON:0000331	63.07	silver quality
cortical plate	UBERON:0005343	62.38	gold quality
monocyte	CL:0000576	61.83	gold quality
right lobe of liver	UBERON:0001114	61.42	gold quality
leukocyte	CL:0000738	61.33	gold quality
skin of leg	UBERON:0001511	61.12	gold quality
right adrenal gland	UBERON:0001233	61.08	gold quality
body of pancreas	UBERON:0001150	61.06	gold quality
metanephros cortex	UBERON:0010533	61.06	gold quality
left lobe of thyroid gland	UBERON:0001120	61.01	gold quality
stromal cell of endometrium	CL:0002255	60.94	gold quality
skin of abdomen	UBERON:0001416	60.94	gold quality
right lobe of thyroid gland	UBERON:0001119	60.80	gold quality
right adrenal gland cortex	UBERON:0035827	60.66	gold quality
thyroid gland	UBERON:0002046	60.13	gold quality
granulocyte	CL:0000094	59.89	gold quality
adenohypophysis	UBERON:0002196	59.84	gold quality
smooth muscle tissue	UBERON:0001135	59.69	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	59.58	gold quality
pancreas	UBERON:0001264	59.36	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.89

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• In the analysis of the genotype tissue expression (GTEx) project datasets, HAL rs17676826 C and NOXRED1 rs8012548 G alleles were significantly associated with their mRNA expression levels in sun-exposed skin of the lower leg (P = 6.62 x 10(-6) and 1.37 x 10(-7) , respectively) and in sun-not-exposed suprapubic skin (P < .001 and 1.43 x 10(-8) , respectively). (PMID:31435991)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	noxred1	ENSDARG00000027538
mus_musculus	Noxred1	ENSMUSG00000072919
rattus_norvegicus	Noxred1	ENSRNOG00000047312
drosophila_melanogaster	P5cr	FBGN0015781
caenorhabditis_elegans		WBGENE00018904

Paralogs (3): PYCR3 (ENSG00000104524), PYCR2 (ENSG00000143811), PYCR1 (ENSG00000183010)

Protein

Protein identifiers

NADP-dependent oxidoreductase domain-containing protein 1 — Q6NXP6 (reviewed: Q6NXP6)

Alternative names: Pyrroline-5-carboxylate reductase-like protein C14orf148

All UniProt accessions (2): G3V2D4, Q6NXP6

UniProt curated annotations — full annotation on UniProt →

Function. Probable oxidoreductase.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the pyrroline-5-carboxylate reductase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6NXP6-1	1	yes
Q6NXP6-2	2

RefSeq proteins (2): NP_001106946, NP_001381909 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028939	P5C_Rdtase_cat_N	Domain
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily

Pfam: PF03807

UniProt features (4 total): sequence conflict 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6NXP6-F1	86.98	0.69

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 61 (showing top): GOBP_GLUTAMINE_FAMILY_AMINO_ACID_BIOSYNTHETIC_PROCESS, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, GOBP_AMINO_ACID_BIOSYNTHETIC_PROCESS, GOBP_GLUTAMINE_FAMILY_AMINO_ACID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, chr14q24, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_THE_CH_NH_GROUP_OF_DONORS, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_THE_CH_NH_GROUP_OF_DONORS_NAD_OR_NADP_AS_ACCEPTOR, GOBP_PROLINE_METABOLIC_PROCESS, MIR1468_3P, MIR548AW, MIR450B_5P, MIR5584_5P

GO Biological Process (2): L-proline biosynthetic process (GO:0055129), biological_process (GO:0008150)

GO Molecular Function (3): pyrroline-5-carboxylate reductase activity (GO:0004735), molecular_function (GO:0003674), oxidoreductase activity (GO:0016491)

GO Cellular Component (1): cellular_component (GO:0005575)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
L-proline metabolic process	1
glutamate family amino acid biosynthetic process	1
oxidoreductase activity, acting on the CH-NH group of donors, NAD or NADP as acceptor	1
catalytic activity	1

Protein interactions and networks

STRING

746 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NOXRED1	SLIRP-OT1	Q8N769	608
NOXRED1	TMEM253	P0C7T8	580
NOXRED1	TMED8	Q6PL24	575
NOXRED1	LGSN	Q5TDP6	529
NOXRED1	SAMD15	Q9P1V8	509
NOXRED1	PYCR3	Q53H96	450
NOXRED1	TMEM50A	O95807	447
NOXRED1	C6orf89	Q6UWU4	436
NOXRED1	ALDH18A1	P54886	425
NOXRED1	C1orf56	Q9BUN1	406
NOXRED1	AGMAT	Q9BSE5	402
NOXRED1	ADSL	P30566	401
NOXRED1	SLC6A16	Q9GZN6	394
NOXRED1	UROC1	Q96N76	392
NOXRED1	ISM2	Q6H9L7	391

IntAct

3 interactions, top by confidence:

A	B	Type	Score
NOXRED1	MPZL1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (3): MPZL1 (Affinity Capture-MS), MPZL1 (Affinity Capture-MS), MPZL1 (Affinity Capture-MS)

ESM2 similar proteins: A0JM24, A1A5R7, A2AKG8, A2CI34, D3YWQ0, F1MAB7, F6S215, O08653, O43149, O54705, O62699, P29477, P35608, P59438, P97499, Q06518, Q08DB2, Q20CR4, Q27995, Q28314, Q4R856, Q4TVR5, Q4VSN2, Q4VSN3, Q4VSN4, Q4VSN5, Q5BIW4, Q5EB20, Q5R6T6, Q5SSH7, Q5TEA3, Q5VW36, Q6NV72, Q6NXH8, Q6NXP6, Q6P996, Q6XUX0, Q6XUX1, Q6XUX2, Q6XUX3

Diamond homologs: A0JM24, Q6NXP6, Q9D3S5, A0A348AXY1, A1L2Q8, O04016, O66553, P0A9L8, P0A9L9, P0C1E4, P0C1E5, P17817, P22008, P27771, P32322, P43869, P46725, P52053, P54552, P54893, P54904, P74572, P9WHU6, P9WHU7, Q04708, Q12641, Q17QJ7, Q20848, Q4R531, Q4R6W7, Q53H96, Q58D08, Q58DT4, Q5PQJ6, Q5R9X6, Q5RAQ3, Q5SPD7, Q6AY23, Q922Q4, Q922W5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	52
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1111 predictions. Top by Δscore:

Variant	Effect	Δscore
14:77406747:G:C	donor_gain	1.0000
14:77406786:C:CA	donor_gain	1.0000
14:77406700:G:A	donor_gain	0.9900
14:77407645:CCTG:C	acceptor_loss	0.9800
14:77407646:CTGG:C	acceptor_loss	0.9800
14:77407647:T:C	acceptor_loss	0.9800
14:77406132:CCCC:C	acceptor_gain	0.9700
14:77406133:CCCC:C	acceptor_gain	0.9700
14:77406720:TG:T	donor_gain	0.9700
14:77406721:G:T	donor_gain	0.9700
14:77405916:T:A	donor_gain	0.9600
14:77406136:C:CG	acceptor_loss	0.9600
14:77406137:T:G	acceptor_loss	0.9600
14:77406138:A:C	acceptor_loss	0.9500
14:77406717:CCG:C	donor_gain	0.9400
14:77406725:A:T	donor_gain	0.9400
14:77406718:CG:C	donor_gain	0.9300
14:77406133:CCC:C	acceptor_gain	0.9200
14:77406134:CCC:C	acceptor_gain	0.9200
14:77406787:C:A	donor_gain	0.9200
14:77405907:CCTTA:C	donor_loss	0.9100
14:77405908:CTTA:C	donor_loss	0.9100
14:77405909:TTA:T	donor_loss	0.9100
14:77405910:TACCT:T	donor_loss	0.9100
14:77405911:A:C	donor_loss	0.9100
14:77405912:C:CT	donor_loss	0.9100
14:77394806:C:CC	acceptor_gain	0.9000
14:77411949:G:C	donor_gain	0.9000
14:77414126:CT:C	acceptor_gain	0.9000
14:77414128:C:CC	acceptor_gain	0.9000

AlphaMissense

2339 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:77407491:G:C	S168R	0.991
14:77407491:G:T	S168R	0.991
14:77407493:T:G	S168R	0.991
14:77407566:G:C	C143W	0.982
14:77406112:A:G	W236R	0.979
14:77406112:A:T	W236R	0.979
14:77407568:A:G	C143R	0.972
14:77407573:A:G	F141S	0.969
14:77406080:G:C	N246K	0.968
14:77406080:G:T	N246K	0.968
14:77407549:A:G	L149P	0.965
14:77414021:C:A	G88W	0.964
14:77422769:C:G	A41P	0.964
14:77407563:G:C	C144W	0.962
14:77394790:A:C	F307L	0.960
14:77394790:A:T	F307L	0.960
14:77394792:A:G	F307L	0.960
14:77407498:A:T	V166E	0.959
14:77407572:G:C	F141L	0.959
14:77407572:G:T	F141L	0.959
14:77407574:A:G	F141L	0.959
14:77407565:A:G	C144R	0.958
14:77414035:C:T	G83E	0.958
14:77407496:A:C	Y167D	0.955
14:77407567:C:T	C143Y	0.954
14:77414041:A:G	I81T	0.954
14:77414008:G:T	A92D	0.953
14:77407586:C:G	A137P	0.948
14:77407597:A:G	L133P	0.947
14:77414038:A:T	I82N	0.946

dbSNP variants (sampled 300 via entrez): RS1000003882 (14:77424840 G>C), RS1000067040 (14:77401625 G>A), RS1000086100 (14:77417214 C>A,T), RS1000333577 (14:77401273 G>C), RS1000493967 (14:77398636 T>C), RS1000511131 (14:77420596 T>A,C), RS1000562483 (14:77417449 G>A), RS1000648383 (14:77420939 G>A), RS1000675644 (14:77413428 A>G,T), RS1000730235 (14:77406493 G>C), RS1000731175 (14:77405804 T>C), RS1000782689 (14:77427138 C>A), RS1000783154 (14:77406838 G>A), RS1000942010 (14:77399654 T>C), RS1000954091 (14:77412671 C>T)

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

4 associations (top):

Study	Trait	p-value
GCST004610_139	White blood cell count	2.000000e-09
GCST004614_17	Granulocyte count	2.000000e-12
GCST004620_87	Sum basophil neutrophil counts	8.000000e-12
GCST004626_128	Myeloid white cell count	2.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007987	granulocyte count
EFO:0004833	neutrophil count
EFO:0005090	basophil count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	increases expression	1
ferrous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
Arbutin	decreases expression	1
Folic Acid	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1

Clinical trials (associated diseases)

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