NEFM

Summary

NEFM (neurofilament medium chain, HGNC:7734) is a protein-coding gene on chromosome 8p21.2, encoding Neurofilament medium polypeptide (P07197). Neurofilaments usually contain three intermediate filament proteins: NEFL, NEFM, and NEFH which are involved in the maintenance of neuronal caliber.

Neurofilaments are type IV intermediate filament heteropolymers composed of light, medium, and heavy chains. Neurofilaments comprise the axoskeleton and functionally maintain neuronal caliber. They may also play a role in intracellular transport to axons and dendrites. This gene encodes the medium neurofilament protein. This protein is commonly used as a biomarker of neuronal damage. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

Source: NCBI Gene 4741 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 136 total
• Druggable target: yes
• MANE Select transcript: NM_005382

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7734
Approved symbol	NEFM
Name	neurofilament medium chain
Location	8p21.2
Locus type	gene with protein product
Status	Approved
Aliases	NFM, NF-M
Ensembl gene	ENSG00000104722
Ensembl biotype	protein_coding
OMIM	162250
Entrez	4741

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000221166, ENST00000433454, ENST00000437366, ENST00000518131, ENST00000521540, ENST00000523467

RefSeq mRNA: 2 — MANE Select: NM_005382 NM_001105541, NM_005382

CCDS: CCDS47831, CCDS6046

Canonical transcript exons

ENST00000221166 — 3 exons

Exon	Start	End
ENSE00000684992	24917061	24919093
ENSE00001215498	24913761	24914873
ENSE00003643795	24915605	24915729

Expression profiles

Bgee: expression breadth ubiquitous, 212 present calls, max score 99.93.

FANTOM5 (CAGE): breadth broad, TPM avg 52.5790 / max 14708.2955, expressed in 670 samples.

FANTOM5 promoters (16 alternative TSS)

Promoter ID	TPM avg	Samples expressed
87972	34.6493	650
87982	4.8045	225
87986	2.4707	203
87989	2.4178	207
87985	1.5900	130
87984	1.4641	145
87980	1.2795	141
87983	0.9771	79
87981	0.8046	92
87992	0.6582	101

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
dorsal root ganglion	UBERON:0000044	99.93	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.92	gold quality
pons	UBERON:0000988	99.89	gold quality
middle temporal gyrus	UBERON:0002771	99.80	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.78	gold quality
endothelial cell	CL:0000115	99.56	gold quality
superior vestibular nucleus	UBERON:0007227	99.52	gold quality
substantia nigra pars compacta	UBERON:0001965	99.43	gold quality
primary visual cortex	UBERON:0002436	99.37	gold quality
frontal pole	UBERON:0002795	99.16	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.12	gold quality
lateral globus pallidus	UBERON:0002476	99.00	gold quality
medulla oblongata	UBERON:0001896	98.94	gold quality
parietal lobe	UBERON:0001872	98.92	gold quality
Brodmann (1909) area 10	UBERON:0013541	98.89	gold quality
occipital lobe	UBERON:0002021	98.87	gold quality
postcentral gyrus	UBERON:0002581	98.87	gold quality
superior frontal gyrus	UBERON:0002661	98.78	gold quality
Brodmann (1909) area 46	UBERON:0006483	98.70	gold quality
orbitofrontal cortex	UBERON:0004167	98.57	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	98.50	gold quality
trigeminal ganglion	UBERON:0001675	98.48	gold quality
right frontal lobe	UBERON:0002810	98.27	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.27	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	98.18	gold quality
frontal cortex	UBERON:0001870	98.01	gold quality
frontal lobe	UBERON:0016525	98.01	gold quality
ventral tegmental area	UBERON:0002691	97.78	gold quality
cerebral cortex	UBERON:0000956	97.49	gold quality
neocortex	UBERON:0001950	97.46	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-HCAD-56	yes	7144.07
E-MTAB-7316	yes	2003.93
E-HCAD-25	yes	1493.41
E-MTAB-11121	yes	1434.74
E-MTAB-9154	yes	1051.16
E-GEOD-75140	yes	912.68
E-MTAB-6524	yes	426.79
E-HCAD-5	yes	10.20
E-GEOD-93593	yes	8.07
E-ANND-3	yes	3.10

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CHD8, MYC

miRNA regulators (miRDB)

25 targeting NEFM, 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-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-135A-5P	99.36	71.85	1601
HSA-MIR-135B-5P	99.36	71.63	1613
HSA-MIR-6507-3P	99.35	67.32	1059
HSA-MIR-501-3P	99.33	66.12	651
HSA-MIR-502-3P	99.33	66.12	651
HSA-MIR-3160-5P	99.28	69.07	1938
HSA-MIR-3973	99.20	69.19	1990
HSA-MIR-1294	98.91	69.26	1030
HSA-MIR-9986	98.91	69.28	1024
HSA-MIR-4726-3P	98.49	63.89	1385
HSA-MIR-6826-3P	98.19	66.32	1153
HSA-MIR-1279	97.83	67.50	1898
HSA-MIR-6859-3P	97.26	64.69	428
HSA-MIR-6759-3P	96.94	68.31	823
HSA-MIR-3943	95.87	64.57	523

Literature-anchored findings (GeneRIF, showing 18)

• To study if the increase of levels of neurofilament (NF)-M and NF-L in brain of Alzheimer’s diseases (AD) is caused by increase of NF-M and NF-L. (PMID:12133495)
• Two polymorphisms of neurofilament M(Ala475Thr and Gly697Arg) occurred at similar frequencies in PD patients and controls. A Pro725Gln substitution and a deletion of valine in position 829 were identified in two PD patients. (PMID:14583397)
• The G336S variant of hNF-M does not affect the formation of IF networks nor the distribution of the variant hNFM protein. If the G336S variant is involved in the development of PD, it isn’t due to defects in the assembly and distribution of NFs. (PMID:15290901)
• O-glycosylation of NF-M is highly dynamic and closely interwoven with phosphorylation cascades and may have a pathophysiological role. (PMID:16006557)
• mutations in neurofilaments are possible risk factors that may contribute to pathogenesis in amytrophic lateral sclerosis in conjunction with one or more additional genetic or environmental factors, but are not significant primary causes (PMID:16084104)
• variation in NEF3 influence rate of response to typical antipsychotic medication (PMID:16734940)
• This protein has been found differentially expressed in the temporal lobe from patients with schizophrenia. (PMID:19034380)
• the importance of alpha-internexin and NF-L in regulating the conformations of NF-M and NF-H (PMID:20213320)
• This protein has been found differentially expressed in the anterior cingulate cortex from patients with schizophrenia (PMID:20381070)
• This protein has been found differentially expressed in thalami from patients with schizophrenia. (PMID:20471030)
• direct evidence that NF-M/H are hyperphosphorylated in Alzheimer disease (PMID:20624930)
• There was a strongly elevated reactivity against neurofilament medium in a subset of schizophrenia patients compared to controls. (PMID:24636402)
• NEFM is a negative regulator of aldosterone production and cell proliferation, in part by facilitating D1R internalization from the plasma membrane in Adosterone-producing Adenomas. (PMID:28584012)
• Study determined that spinophilin binding to neurofilament medium required overexpression of the catalytic subunit of protein kinase A and was decreased by cyclin-dependent protein kinase 5. (PMID:28634551)
• the regulation of NEFM and NEFH mRNA levels by miRNAs, was investigated. (PMID:30029677)
• LINC00294 negatively modulates cell proliferation in glioma through a neurofilament medium-mediated pathway via interacting with miR-1278. (PMID:32450002)
• NEFM DNA methylation correlates with immune infiltration and survival in breast cancer. (PMID:34001208)
• Neurodegeneration Markers in the Cerebrospinal Fluid of 100 Patients with Schizophrenia Spectrum Disorder. (PMID:36200879)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
rattus_norvegicus	Nefm	ENSRNOG00000013916

Paralogs (68): KRT33A (ENSG00000006059), VIM (ENSG00000026025), KRT31 (ENSG00000094796), KRT23 (ENSG00000108244), KRT37 (ENSG00000108417), KRT32 (ENSG00000108759), KRT18 (ENSG00000111057), LMNB1 (ENSG00000113368), KRT36 (ENSG00000126337), KRT17 (ENSG00000128422), GFAP (ENSG00000131095), KRT34 (ENSG00000131737), KRT33B (ENSG00000131738), NES (ENSG00000132688), PRPH (ENSG00000135406), KRT85 (ENSG00000135443), KRT7 (ENSG00000135480), KRT71 (ENSG00000139648), INA (ENSG00000148798), LMNTD1 (ENSG00000152936), LMNA (ENSG00000160789), KRT84 (ENSG00000161849), KRT82 (ENSG00000161850), KRT80 (ENSG00000167767), KRT1 (ENSG00000167768), KRT24 (ENSG00000167916), KRT8 (ENSG00000170421), KRT78 (ENSG00000170423), KRT86 (ENSG00000170442), KRT75 (ENSG00000170454), KRT6C (ENSG00000170465), KRT4 (ENSG00000170477), KRT74 (ENSG00000170484), KRT72 (ENSG00000170486), KRT83 (ENSG00000170523), BFSP2 (ENSG00000170819), KRT19 (ENSG00000171345), KRT15 (ENSG00000171346), KRT38 (ENSG00000171360), KRT13 (ENSG00000171401)

Protein

Protein identifiers

Neurofilament medium polypeptide — P07197 (reviewed: P07197)

Alternative names: 160 kDa neurofilament protein, Neurofilament 3, Neurofilament triplet M protein

All UniProt accessions (3): E7EMV2, E7ESP9, P07197

UniProt curated annotations — full annotation on UniProt →

Function. Neurofilaments usually contain three intermediate filament proteins: NEFL, NEFM, and NEFH which are involved in the maintenance of neuronal caliber. May additionally cooperate with the neuronal intermediate filament proteins PRPH and INA to form neuronal filamentous networks.

Subunit / interactions. Forms heterodimers with NEFL; which can further hetero-oligomerize (in vitro). Forms heterodimers with INA (in vitro).

Subcellular location. Cytoplasm. Cytoskeleton. Cell projection. Axon. Perikaryon.

Post-translational modifications. There are a number of repeats of the tripeptide K-S-P, NFM is phosphorylated on a number of the serines in this motif. It is thought that phosphorylation of NFM results in the formation of interfilament cross bridges that are important in the maintenance of axonal caliber. Phosphorylation seems to play a major role in the functioning of the larger neurofilament polypeptides (NF-M and NF-H), the levels of phosphorylation being altered developmentally and coincidentally with a change in the neurofilament function. Phosphorylated in the head and rod regions by the PKC kinase PKN1, leading to the inhibition of polymerization.

Similarity. Belongs to the intermediate filament family.

Isoforms (2)

UniProt ID	Names	Canonical?
P07197-1	1	yes
P07197-2	2

RefSeq proteins (2): NP_001099011, NP_005373* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002957	Keratin_I	Family
IPR006821	Intermed_filament_DNA-bd	Domain
IPR018039	IF_conserved	Conserved_site
IPR039008	IF_rod_dom	Domain
IPR050405	Intermediate_filament	Family

Pfam: PF00038, PF04732

UniProt features (63 total): modified residue 24, region of interest 12, compositionally biased region 12, repeat 6, glycosylation site 2, sequence variant 2, initiator methionine 1, chain 1, domain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P07197-F1	58.26	0.27

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 (24): 2, 30, 42, 99, 226, 320, 346, 418, 467, 483, 511, 545, 553, 558, 559, 571, 641, 646, 680, 685 …

Glycosylation sites (2): 47, 431

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 170 (showing top): BENPORATH_ES_WITH_H3K27ME3, GOBP_INTERMEDIATE_FILAMENT_BASED_PROCESS, GOBP_INTERMEDIATE_FILAMENT_ORGANIZATION, RORA1_01, ENK_UV_RESPONSE_KERATINOCYTE_UP, AAGCCAT_MIR135A_MIR135B, BROWNE_HCMV_INFECTION_16HR_UP, TGACCTY_ERR1_Q2, BROWNE_HCMV_INFECTION_12HR_UP, MODULE_66, SMITH_TERT_TARGETS_DN, chr8p21, KIM_RESPONSE_TO_TSA_AND_DECITABINE_UP, TGANTCA_AP1_C, AACTTT_UNKNOWN

GO Biological Process (1): neurofilament bundle assembly (GO:0033693)

GO Molecular Function (4): structural constituent of cytoskeleton (GO:0005200), microtubule binding (GO:0008017), structural molecule activity (GO:0005198), protein binding (GO:0005515)

GO Cellular Component (9): intermediate filament (GO:0005882), neurofilament (GO:0005883), axon (GO:0030424), intermediate filament cytoskeleton (GO:0045111), neurofibrillary tangle (GO:0097418), postsynaptic intermediate filament cytoskeleton (GO:0099160), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoskeleton	2
intermediate filament cytoskeleton	2
cellular anatomical structure	2
intermediate filament bundle assembly	1
structural molecule activity	1
cytoskeleton organization	1
tubulin binding	1
molecular_function	1
binding	1
polymeric cytoskeletal fiber	1
cytoplasm	1
intermediate filament	1
neuron projection	1
inclusion body	1
postsynapse	1
postsynaptic cytoskeleton	1
intracellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

3164 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NEFM	NEFL	P07196	988
NEFM	NEFH	P12036	985
NEFM	INA	Q16352	982
NEFM	ARHGEF28	Q8N1W1	774
NEFM	MAPT	P10636	683
NEFM	SOD1	P00441	676
NEFM	CRYAB	P02511	582
NEFM	CDK5	Q00535	552
NEFM	FUS	P35637	544
NEFM	CHAT	P28329	524
NEFM	SNCA	P37840	519
NEFM	SLC1A2	P43004	514
NEFM	KIF1A	Q12756	514
NEFM	MAP2	P11137	506
NEFM	HNRNPK	P61978	487

IntAct

117 interactions, top by confidence:

A	B	Type	Score
NEFM	VIM	psi-mi:“MI:0915”(physical association)	0.910
GFAP	NEFL	psi-mi:“MI:0914”(association)	0.850
VIM	NEFL	psi-mi:“MI:0914”(association)	0.840
CAPN1	CAPNS1	psi-mi:“MI:0914”(association)	0.840
NEFM	NEFL	psi-mi:“MI:0914”(association)	0.800
NEFL	NEFM	psi-mi:“MI:0915”(physical association)	0.800
KRT31	HGS	psi-mi:“MI:0914”(association)	0.780
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CCDC120	AIP	psi-mi:“MI:0914”(association)	0.640
KSR2	POLR3A	psi-mi:“MI:0914”(association)	0.530
MLLT6	RGPD8	psi-mi:“MI:0914”(association)	0.530
RSPRY1	NEFL	psi-mi:“MI:0914”(association)	0.530
CCDC106	NEFM	psi-mi:“MI:0914”(association)	0.530
NUP62	RGPD8	psi-mi:“MI:0914”(association)	0.530
NEFM	EVI5	psi-mi:“MI:0914”(association)	0.530
NEFM	VWA8	psi-mi:“MI:0914”(association)	0.530
NEFM	RB1	psi-mi:“MI:0915”(physical association)	0.520
NEFM	HSPD1	psi-mi:“MI:0915”(physical association)	0.400
NEFM	FHAD1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (266): NEFM (Affinity Capture-MS), NEFM (Affinity Capture-MS), NEFM (Affinity Capture-MS), NEFM (Affinity Capture-MS), CALD1 (Affinity Capture-MS), SS18 (Affinity Capture-MS), DNAJA2 (Affinity Capture-MS), STOML2 (Affinity Capture-MS), RPRD1B (Affinity Capture-MS), DNTTIP1 (Affinity Capture-MS), NEFM (Affinity Capture-MS), NEFM (Affinity Capture-MS), DES (Affinity Capture-MS), INA (Affinity Capture-MS), NEFM (Affinity Capture-MS)

ESM2 similar proteins: A2ASS6, A8DYP0, E9QMW4, G4SLH0, J7M799, M9MRD1, O15061, O43491, O55103, O70318, O75952, O77788, P07197, P08553, P08855, P11799, P12839, P16053, P27321, P51125, P54938, P57786, P82179, P83741, Q06637, Q13061, Q23551, Q28820, Q4R3X7, Q63425, Q66H38, Q696W0, Q6TS35, Q70IV5, Q7Z589, Q7ZUV7, Q86TC9, Q8BMB0, Q8TC56, Q8WZ42

Diamond homologs: A0A8C0N8E3, A5A6M8, A5A6N0, A6QQJ3, B4F721, O62654, O77788, O93532, O95678, P02538, P02540, P02541, P02542, P02543, P02544, P02547, P02548, P03995, P04259, P05786, P05787, P07196, P07197, P08551, P08552, P08553, P08670, P08729, P08776, P09654, P11679, P12035, P12036, P12839, P13647, P14136, P15331, P16053, P16878, P16884

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
NEFM	up-regulates	“Neurofilament bundle assembly”
NEFM	“form complex”	“Neurofilament L/M”	binding
CDK5	“down-regulates quantity”	NEFM	phosphorylation
CHD8	“down-regulates quantity”	NEFM	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 118 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Formation of the cornified envelope	13	14.3×	3e-09
Keratinization	12	8.4×	5e-06

GO biological processes:

GO term	Partners	Fold	FDR
intermediate filament organization	14	32.1×	8e-15
morphogenesis of an epithelium	8	26.2×	3e-07
epithelial cell differentiation	6	10.0×	1e-02

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	114
Likely benign	2
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

270 predictions. Top by Δscore:

Variant	Effect	Δscore
8:24914873:GGTAG:G	donor_loss	1.0000
8:24914874:GTAGG:G	donor_loss	1.0000
8:24914875:T:A	donor_loss	1.0000
8:24915597:T:TA	acceptor_gain	1.0000
8:24915603:A:AG	acceptor_gain	1.0000
8:24915603:AG:A	acceptor_gain	1.0000
8:24915603:AGGAC:A	acceptor_loss	1.0000
8:24915604:G:GG	acceptor_gain	1.0000
8:24915604:G:GT	acceptor_loss	1.0000
8:24915604:GG:G	acceptor_gain	1.0000
8:24915604:GGA:G	acceptor_gain	1.0000
8:24915604:GGAC:G	acceptor_gain	1.0000
8:24915604:GGACA:G	acceptor_gain	1.0000
8:24915726:ACAG:A	donor_loss	1.0000
8:24915728:AG:A	donor_loss	1.0000
8:24915729:GGT:G	donor_loss	1.0000
8:24915730:GT:G	donor_loss	1.0000
8:24914874:G:GG	donor_gain	0.9900
8:24915602:CAGGA:C	acceptor_gain	0.9900
8:24915730:G:GG	donor_gain	0.9900
8:24917059:A:AG	acceptor_gain	0.9900
8:24917060:G:GG	acceptor_gain	0.9900
8:24915598:GTTTC:G	acceptor_loss	0.9800
8:24915603:AGGA:A	acceptor_gain	0.9800
8:24915809:T:G	donor_gain	0.9800
8:24917045:T:A	acceptor_gain	0.9800
8:24917060:GA:G	acceptor_gain	0.9800
8:24917060:GAA:G	acceptor_gain	0.9800
8:24917060:GAAA:G	acceptor_gain	0.9800
8:24915601:TCAGG:T	acceptor_gain	0.9700

AlphaMissense

6006 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:24914107:T:C	L105P	1.000
8:24914116:T:A	L108Q	1.000
8:24914116:T:C	L108P	1.000
8:24914120:C:A	N109K	1.000
8:24914120:C:G	N109K	1.000
8:24914125:G:C	R111P	1.000
8:24914128:T:C	F112S	1.000
8:24914128:T:G	F112C	1.000
8:24914158:T:C	L122P	1.000
8:24914473:T:C	L227P	1.000
8:24914490:T:C	F233L	1.000
8:24914492:C:A	F233L	1.000
8:24914492:C:G	F233L	1.000
8:24914494:T:C	L234P	1.000
8:24914527:T:C	L245P	1.000
8:24914602:T:A	L270Q	1.000
8:24914602:T:C	L270P	1.000
8:24914611:T:C	I273T	1.000
8:24914611:T:G	I273S	1.000
8:24914613:C:A	R274S	1.000
8:24914614:G:C	R274P	1.000
8:24914623:T:C	L277P	1.000
8:24914667:T:C	F292L	1.000
8:24914668:T:C	F292S	1.000
8:24914669:C:A	F292L	1.000
8:24914669:C:G	F292L	1.000
8:24914677:G:C	R295P	1.000
8:24914689:T:A	L299H	1.000
8:24914689:T:C	L299P	1.000
8:24914697:G:C	A302P	1.000

dbSNP variants (sampled 300 via entrez): RS1000384489 (8:24914797 G>A), RS1000436906 (8:24915072 C>T), RS1000936027 (8:24914984 G>A,C), RS1001320006 (8:24915453 G>A,T), RS1003403855 (8:24916600 C>T), RS1003863985 (8:24916903 A>C,G), RS1004329551 (8:24914613 C>A,T), RS1005412293 (8:24913747 G>A), RS1006413309 (8:24916008 T>C), RS1007295432 (8:24912749 C>T), RS1007379158 (8:24913946 C>G,T), RS1007412893 (8:24916178 T>A), RS1007465129 (8:24916537 C>G), RS1007758556 (8:24912975 C>G), RS1008083657 (8:24919081 T>C)

Disease associations

OMIM: gene MIM:162250 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST004708_10	Fear of minor pain	1.000000e-08
GCST005588_38	Idiopathic dilated cardiomyopathy	5.000000e-06
GCST006103_3	Interleukin-6 levels	2.000000e-07
GCST009391_977	Metabolite levels	2.000000e-06
GCST010703_64	Brain morphology (MOSTest)	2.000000e-08

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0008340	fear of minor pain measurement
EFO:0009094	idiopathic dilated cardiomyopathy
EFO:0004810	interleukin-6 measurement
EFO:0010538	taurocholate measurement
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066976 (SINGLE PROTEIN)

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1379357	NEFM		0.00	0
rs1457266	NEFM		0.00	0

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.34	Kd	452.6	nM	CHEMBL5653589
6.08	ED50	841.7	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148859: Binding affinity to human NEFM incubated for 45 mins by Kinobead based pull down assay	kd	0.4526	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	9
Tretinoin	affects cotreatment, increases expression, increases phosphorylation	4
trichostatin A	increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
entinostat	decreases expression, increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Arsenic	affects expression, decreases expression, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
FR900359	increases phosphorylation	1
methylmercuric chloride	increases expression	1
propionaldehyde	increases expression	1
bisphenol A	decreases expression	1
sodium arsenate	decreases expression, increases abundance	1
N(4)-hydroxycytidine	increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
terbufos	increases methylation	1
arsenite	increases methylation	1
afimoxifene	decreases reaction, decreases expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
ferrous chloride	increases expression	1
5-iodotubercidin	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
gallium arsenide	increases expression	1
pentanal	increases expression	1
nutlin 3	increases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651901	Binding	Binding affinity to human NEFM incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3C8	Abcam HEK293T NEFM KO	Transformed cell line	Female

Clinical trials (associated diseases)

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