NENF

Summary

NENF (neudesin neurotrophic factor, HGNC:30384) is a protein-coding gene on chromosome 1q32.3, encoding Neudesin (Q9UMX5). Acts as a neurotrophic factor in postnatal mature neurons enhancing neuronal survival.

This gene encodes a neurotrophic factor that may play a role in neuron differentiation and development. A pseudogene of this gene is found on chromosome 12. Alternate splicing of this gene results in multiple transcript variants.

Source: NCBI Gene 29937 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 24 total
• MANE Select transcript: NM_013349

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30384
Approved symbol	NENF
Name	neudesin neurotrophic factor
Location	1q32.3
Locus type	gene with protein product
Status	Approved
Aliases	CIR2, SCIRP10, SPUF
Ensembl gene	ENSG00000117691
Ensembl biotype	protein_coding
OMIM	611874
Entrez	29937

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000366988, ENST00000472389, ENST00000473900, ENST00000479589, ENST00000896950, ENST00000949004, ENST00000949005

RefSeq mRNA: 1 — MANE Select: NM_013349 NM_013349

CCDS: CCDS1505

Canonical transcript exons

ENST00000366988 — 4 exons

Exon	Start	End
ENSE00000841424	212442565	212442625
ENSE00001816583	212432920	212433120
ENSE00003557378	212444339	212444442
ENSE00003654692	212445830	212446379

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 98.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 77.5446 / max 510.2672, expressed in 1827 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
8456	70.9399	1827
8455	3.5241	1583
8454	3.0807	1548

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	98.86	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.70	gold quality
adenohypophysis	UBERON:0002196	98.53	gold quality
pituitary gland	UBERON:0000007	98.38	gold quality
spinal cord	UBERON:0002240	98.16	gold quality
putamen	UBERON:0001874	98.09	gold quality
caudate nucleus	UBERON:0001873	98.02	gold quality
nucleus accumbens	UBERON:0001882	98.02	gold quality
medial globus pallidus	UBERON:0002477	98.01	gold quality
apex of heart	UBERON:0002098	97.81	gold quality
right coronary artery	UBERON:0001625	97.59	gold quality
type B pancreatic cell	CL:0000169	97.40	gold quality
descending thoracic aorta	UBERON:0002345	97.37	gold quality
globus pallidus	UBERON:0001875	97.36	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.35	gold quality
ascending aorta	UBERON:0001496	97.33	gold quality
thoracic aorta	UBERON:0001515	97.33	gold quality
amygdala	UBERON:0001876	97.31	gold quality
right atrium auricular region	UBERON:0006631	97.26	gold quality
left ovary	UBERON:0002119	97.13	gold quality
endocervix	UBERON:0000458	97.12	gold quality
left coronary artery	UBERON:0001626	97.11	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.11	gold quality
right ovary	UBERON:0002118	97.04	gold quality
coronary artery	UBERON:0001621	97.03	gold quality
aorta	UBERON:0000947	96.98	gold quality
hypothalamus	UBERON:0001898	96.83	gold quality
mucosa of stomach	UBERON:0001199	96.81	gold quality
cardiac atrium	UBERON:0002081	96.81	gold quality
popliteal artery	UBERON:0002250	96.79	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-9154	yes	1677.93
E-GEOD-81547	yes	590.75
E-ANND-3	yes	19.43
E-HCAD-1	yes	7.98
E-MTAB-5061	no	574.03
E-GEOD-81608	no	122.89
E-CURD-114	no	20.46

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

44 targeting NENF, 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-340-5P	100.00	72.50	4437
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-888-3P	99.53	69.77	1057
HSA-MIR-3609	99.52	69.89	2587

Literature-anchored findings (GeneRIF, showing 6)

• Human neudesin of 172 amino acids with high similarity ( approximately 91% identity) to mouse neudesin was identified; the human neudesin gene was mapped to chromosome 1p33. (PMID:15605373)
• Describes the predicted heme-binding domains in the human neudesin protein sequence. (PMID:18056703)
• High NENF expression is associated with liver cancer. (PMID:24763612)
• In astrocytic brain tumor patients neudesin concentrations within the cerebrospinal fluid are higher compared with non-tumoral individuals. Serum neudesin concentration strongly correlates with its CSF level. In primary brain tumor patients serum neudesin concentration is clearly gender-dependent. (PMID:30953468)
• Neudesin: a neuropeptide hormone decreased in subjects with polycystic ovary syndrome. (PMID:32314607)
• The level of the neudesin in type-2 diabetic patients and the relationship between the metabolic parameters and carotid intima-media thickness. (PMID:33435641)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
danio_rerio	nenf	ENSDARG00000040192
mus_musculus	Nenf	ENSMUSG00000037499

Protein

Protein identifiers

Neudesin — Q9UMX5 (reviewed: Q9UMX5)

Alternative names: Cell immortalization-related protein 2, Neuron-derived neurotrophic factor, Protein GIG47, Secreted protein of unknown function

All UniProt accessions (1): Q9UMX5

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a neurotrophic factor in postnatal mature neurons enhancing neuronal survival. Promotes cell proliferation and neurogenesis in undifferentiated neural progenitor cells at the embryonic stage and inhibits differentiation of astrocytes. Its neurotrophic activity is exerted via MAPK1/ERK2, MAPK3/ERK1 and AKT1/AKT pathways. Neurotrophic activity is enhanced by binding to heme. Also acts as an anorexigenic neurotrophic factor that contributes to energy balance.

Subunit / interactions. Interacts with PINK1 and PARK7.

Subcellular location. Secreted. Extracellular space. Mitochondrion. Endoplasmic reticulum.

Tissue specificity. Ubiquitously expressed with high expression in heart. Over-expressed in various tumors including carcinomas of the uterine cervix, lymphoma, colon, lung, skin and leukemia, as well as carcinoma of the breast.

Domain organisation. The cytochrome b5 heme-binding domain was proven to bind heme, although it lacks the conserved iron-binding His residue at position 82.

Induction. Up-regulated in immortal cells. Induced in estrogen receptor positive breast cancer expressing progesterone receptor.

Miscellaneous. Non-classical progesterone receptors involved in extranuclear signaling are classified in 2 groups: the class II progestin and adipoQ receptor (PAQR) family (also called mPRs) (PAQR5, PAQR6, PAQR7, PAQR8 and PAQR9) and the b5-like heme/steroid-binding protein family (also called MAPRs) (PGRMC1, PGRMC2, NENF and CYB5D2).

Similarity. Belongs to the cytochrome b5 family. MAPR subfamily.

RefSeq proteins (1): NP_037481* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001199	Cyt_B5-like_heme/steroid-bd	Domain
IPR036400	Cyt_B5-like_heme/steroid_sf	Homologous_superfamily
IPR050577	MAPR/NEUFC/NENF-like	Family

Pfam: PF00173

UniProt features (7 total): signal peptide 1, chain 1, domain 1, region of interest 1, compositionally biased region 1, modified residue 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UMX5-F1	73.85	0.42

Functional residue map

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

Post-translational modifications (1): 136

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 136 (showing top): SHEPARD_BMYB_MORPHOLINO_UP, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_RESPONSE_TO_FOOD, GOMF_GROWTH_FACTOR_ACTIVITY, FERREIRA_EWINGS_SARCOMA_UNSTABLE_VS_STABLE_DN, ONKEN_UVEAL_MELANOMA_UP, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM2, GOBP_REGULATION_OF_RESPONSE_TO_FOOD, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_APPETITE, SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_UP, KIM_GASTRIC_CANCER_CHEMOSENSITIVITY, GOMF_SIGNALING_RECEPTOR_BINDING, AIYAR_COBRA1_TARGETS_UP

GO Biological Process (3): MAPK cascade (GO:0000165), negative regulation of appetite (GO:0032099), positive regulation of MAPK cascade (GO:0043410)

GO Molecular Function (3): growth factor activity (GO:0008083), metal ion binding (GO:0046872), protein binding (GO:0005515)

GO Cellular Component (6): obsolete extracellular space (GO:0005615), mitochondrion (GO:0005739), endoplasmic reticulum (GO:0005783), endomembrane system (GO:0012505), membrane (GO:0016020), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoplasm	2
intracellular membrane-bounded organelle	2
intracellular signaling cassette	1
negative regulation of response to food	1
regulation of appetite	1
MAPK cascade	1
regulation of MAPK cascade	1
positive regulation of intracellular signal transduction	1
receptor ligand activity	1
cation binding	1
binding	1
endomembrane system	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

692 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NENF	CYB5B	O43169	962
NENF	CYB5A	P00167	938
NENF	CIRSR	Q86X95	780
NENF	PAQR5	Q9NXK6	532
NENF	PAQR6	Q6TCH4	531
NENF	NUCB2	P80303	521
NENF	PAQR9	Q6ZVX9	502
NENF	KIAA1210	Q9ULL0	477
NENF	PAQR8	Q8TEZ7	475
NENF	CYP4A11	Q02928	459
NENF	PARK7	Q99497	456
NENF	FOXRED2	Q8IWF2	447
NENF	COX6A2	Q02221	446
NENF	PINK1	Q9BXM7	446
NENF	ZNHIT2	Q9UHR6	441

IntAct

12 interactions, top by confidence:

A	B	Type	Score
NENF	BLVRB	psi-mi:“MI:0914”(association)	0.530
PRNP	CARNS1	psi-mi:“MI:0914”(association)	0.350
PRNP	WDR91	psi-mi:“MI:0914”(association)	0.350
	PLOD3	psi-mi:“MI:0914”(association)	0.350
	XRCC6	psi-mi:“MI:0914”(association)	0.350
TCTN1	TOR1A	psi-mi:“MI:2364”(proximity)	0.270
TCTN1	PLOD2	psi-mi:“MI:2364”(proximity)	0.270
EPHA10	PLOD2	psi-mi:“MI:2364”(proximity)	0.270
CFTR	UBA6	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (102): PDIA5 (Affinity Capture-MS), SELM (Affinity Capture-MS), BLVRB (Affinity Capture-MS), NAPRT (Co-fractionation), NENF (Proximity Label-MS), SELM (Affinity Capture-MS), BLVRB (Affinity Capture-MS), PDIA5 (Affinity Capture-MS), NENF (Co-fractionation), NENF (Co-fractionation), NENF (Co-fractionation), NENF (Co-fractionation), POLDIP2 (Co-fractionation), NENF (Co-fractionation), NENF (Co-fractionation)

ESM2 similar proteins: A1ZAX1, A2CES0, A6IPG1, B0W0S3, B3MIF1, B3NML0, B4GIB1, B4HMY3, B4J789, B4KN00, B4LNA1, B4P562, B5ME19, O00264, O13995, O15173, O55022, O70251, O96005, P11035, P16081, P24534, P27967, P27969, P29412, P34826, P70580, Q0ZB76, Q17Q06, Q17QC0, Q1JQA5, Q28Z41, Q2NL17, Q3SYW6, Q5E983, Q5RAT8, Q5RED0, Q5XIU9, Q5ZKN2, Q6DET9

Diamond homologs: A2CES0, O00264, O13995, O15173, O55022, P70580, Q12091, Q17QC0, Q1JQA5, Q28FI8, Q29HF1, Q2HIW2, Q5RED0, Q5SSH8, Q5XIU9, Q5ZKN2, Q60YT6, Q6AY62, Q6IUR5, Q80UU9, Q8WUJ1, Q95250, Q9CQ45, Q9FVZ7, Q9FVZ9, Q9M2Z4, Q9SK39, Q9UMX5, Q9W376, Q9XFM6, Q9XXA7, Q7YZW5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	17
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

505 predictions. Top by Δscore:

Variant	Effect	Δscore
1:212433091:G:GT	donor_gain	1.0000
1:212433118:G:GT	donor_gain	1.0000
1:212442624:GG:G	donor_gain	1.0000
1:212442625:GG:G	donor_gain	1.0000
1:212444332:A:AG	acceptor_gain	1.0000
1:212444333:C:G	acceptor_gain	1.0000
1:212444334:TACAG:T	acceptor_gain	1.0000
1:212444335:ACAGA:A	acceptor_gain	1.0000
1:212444336:C:G	acceptor_gain	1.0000
1:212444336:CAG:C	acceptor_gain	1.0000
1:212444337:A:AC	acceptor_loss	1.0000
1:212444337:A:AG	acceptor_gain	1.0000
1:212444337:AGA:A	acceptor_gain	1.0000
1:212444338:G:GT	acceptor_gain	1.0000
1:212444338:GA:G	acceptor_gain	1.0000
1:212444338:GAG:G	acceptor_gain	1.0000
1:212444338:GAGT:G	acceptor_gain	1.0000
1:212444338:GAGTT:G	acceptor_gain	1.0000
1:212444441:CT:C	donor_gain	1.0000
1:212444442:TG:T	donor_loss	1.0000
1:212444443:G:GC	donor_loss	1.0000
1:212444443:G:GG	donor_gain	1.0000
1:212445812:T:TA	acceptor_gain	1.0000
1:212445813:G:A	acceptor_gain	1.0000
1:212445827:A:AG	acceptor_gain	1.0000
1:212445827:AAGAC:A	acceptor_gain	1.0000
1:212445828:A:G	acceptor_gain	1.0000
1:212445828:AGAC:A	acceptor_gain	1.0000
1:212445828:AGACG:A	acceptor_gain	1.0000
1:212445829:GACG:G	acceptor_gain	1.0000

AlphaMissense

1085 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:212442605:T:C	F73S	0.997
1:212444383:G:C	D95H	0.997
1:212442604:T:C	F73L	0.996
1:212442606:T:A	F73L	0.996
1:212442606:T:G	F73L	0.996
1:212444341:T:C	F81L	0.996
1:212444343:T:A	F81L	0.996
1:212444343:T:G	F81L	0.996
1:212444402:C:A	A101D	0.996
1:212445909:G:T	G141V	0.996
1:212445909:G:A	G141D	0.995
1:212442602:T:A	V72E	0.994
1:212442611:T:A	V75D	0.994
1:212433083:T:C	F47S	0.993
1:212445872:T:C	F129L	0.993
1:212445874:C:A	F129L	0.993
1:212445874:C:G	F129L	0.993
1:212445897:A:G	Y137C	0.993
1:212445908:G:C	G141R	0.993
1:212442605:T:G	F73C	0.991
1:212444390:C:T	T97I	0.991
1:212444395:G:T	G99W	0.991
1:212444384:A:G	D95G	0.990
1:212444410:T:C	S104P	0.990
1:212442586:G:C	A67P	0.989
1:212442587:C:A	A67E	0.989
1:212444396:G:A	G99E	0.989
1:212444401:G:C	A101P	0.989
1:212445908:G:T	G141C	0.989
1:212444372:T:C	L91S	0.988

dbSNP variants (sampled 300 via entrez): RS1000042699 (1:212444625 A>G,T), RS1000093816 (1:212438751 G>T), RS1000889854 (1:212440702 A>T), RS1001004958 (1:212446865 C>T), RS1001036329 (1:212446602 G>C,T), RS1001619268 (1:212442034 C>T), RS1002050401 (1:212441716 G>A), RS1002067098 (1:212437813 T>G), RS1002456686 (1:212437139 A>G), RS1002466395 (1:212436684 T>C), RS1002529609 (1:212437524 T>C), RS1002624442 (1:212433403 T>C), RS1003184210 (1:212440070 G>T), RS1003468398 (1:212434832 G>A), RS1003577112 (1:212432653 G>T)

Disease associations

OMIM: gene MIM:611874 | 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
GCST003772_3	Loneliness (linear analysis)	1.000000e-07
GCST90002393_177	Monocyte count	1.000000e-23

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007865	loneliness measurement
EFO:0005091	monocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	6
bisphenol S	affects expression, increases expression	2
Estradiol	decreases expression, increases expression	2
Cadmium Chloride	increases expression, increases abundance	2
bisphenol A	decreases expression	1
arsenite	increases reaction, affects binding	1
cobaltous chloride	increases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
azoxystrobin	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
picoxystrobin	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Sunitinib	decreases expression	1
Vorinostat	increases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases abundance, increases expression	1
Cisplatin	increases expression	1
Diethylstilbestrol	decreases expression	1
Ivermectin	decreases expression	1
Lead	affects splicing	1
Methapyrilene	decreases methylation	1
Rotenone	increases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Vitamin E	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1

Clinical trials (associated diseases)

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