NDFIP1

Summary

NDFIP1 (Nedd4 family interacting protein 1, HGNC:17592) is a protein-coding gene on chromosome 5q31.3, encoding NEDD4 family-interacting protein 1 (Q9BT67). Activates HECT domain-containing E3 ubiquitin-protein ligases, including NEDD4 and ITCH, and consequently modulates the stability of their targets.

The protein encoded by this gene belongs to a small group of evolutionarily conserved proteins with three transmembrane domains. It is a potential target for ubiquitination by the Nedd4 family of proteins. This protein is thought to be part of a family of integral Golgi membrane proteins.

Source: NCBI Gene 80762 — RefSeq curated summary.

At a glance

• GWAS associations: 47
• Clinical variants (ClinVar): 20 total
• MANE Select transcript: NM_030571

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17592
Approved symbol	NDFIP1
Name	Nedd4 family interacting protein 1
Location	5q31.3
Locus type	gene with protein product
Status	Approved
Aliases	N4WBP5, MGC10924
Ensembl gene	ENSG00000131507
Ensembl biotype	protein_coding
OMIM	612050
Entrez	80762

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 11 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000253814, ENST00000503388, ENST00000505614, ENST00000509436, ENST00000856977, ENST00000856978, ENST00000856979, ENST00000856980, ENST00000856981, ENST00000856982, ENST00000856983, ENST00000927761, ENST00000944182, ENST00000944183

RefSeq mRNA: 1 — MANE Select: NM_030571 NM_030571

CCDS: CCDS4273

Canonical transcript exons

ENST00000253814 — 8 exons

Exon	Start	End
ENSE00000898646	142131808	142131895
ENSE00000898647	142132212	142132342
ENSE00000898649	142137734	142137858
ENSE00000898650	142140563	142140629
ENSE00000898651	142144571	142144676
ENSE00001307497	142151731	142154440
ENSE00001308894	142108779	142109037
ENSE00003654910	142135730	142135817

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 98.0848 / max 1248.7644, expressed in 1825 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
59067	91.1464	1825
59071	3.6657	1424
59068	2.2472	1322
59069	0.4401	228
59070	0.3005	135
59066	0.2850	76

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 23	UBERON:0013554	99.72	gold quality
endothelial cell	CL:0000115	99.66	gold quality
pons	UBERON:0000988	99.35	gold quality
middle temporal gyrus	UBERON:0002771	99.30	gold quality
superior frontal gyrus	UBERON:0002661	99.25	gold quality
entorhinal cortex	UBERON:0002728	99.16	gold quality
postcentral gyrus	UBERON:0002581	99.13	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.13	gold quality
parietal lobe	UBERON:0001872	99.11	gold quality
cortical plate	UBERON:0005343	99.10	gold quality
dorsal root ganglion	UBERON:0000044	99.06	gold quality
primary visual cortex	UBERON:0002436	98.98	gold quality
occipital lobe	UBERON:0002021	98.96	gold quality
corpus epididymis	UBERON:0004359	98.92	gold quality
superior vestibular nucleus	UBERON:0007227	98.85	gold quality
trigeminal ganglion	UBERON:0001675	98.70	gold quality
orbitofrontal cortex	UBERON:0004167	98.64	gold quality
prefrontal cortex	UBERON:0000451	98.63	gold quality
lateral globus pallidus	UBERON:0002476	98.63	gold quality
substantia nigra pars compacta	UBERON:0001965	98.53	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	98.49	gold quality
frontal cortex	UBERON:0001870	98.45	gold quality
frontal lobe	UBERON:0016525	98.45	gold quality
dorsal plus ventral thalamus	UBERON:0001897	98.44	gold quality
cerebral cortex	UBERON:0000956	98.36	gold quality
neocortex	UBERON:0001950	98.36	gold quality
pigmented layer of retina	UBERON:0001782	98.33	gold quality
retina	UBERON:0000966	98.31	gold quality
Brodmann (1909) area 46	UBERON:0006483	98.28	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.27	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	113.97
E-HCAD-5	yes	44.83
E-CURD-112	yes	5.93
E-CURD-77	no	371.28
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

167 targeting NDFIP1, 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-6873-3P	100.00	71.42	2626
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-548P	99.98	72.25	3784
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-3910	99.95	71.13	2227

Literature-anchored findings (GeneRIF, showing 18)

• Ndfip1 is required for the exosomal secretion of Nedd4 family proteins (PMID:18819914)
• Data show that the small PY-containing membrane proteins, NDFIP1 and NDFIP2 (NEDD4 family-interacting proteins), activate the catalytic activity of ITCH and of several other HECT ligases by binding to them. (PMID:19343052)
• Ndfip1 plays a critical role in regulating metal transport in human neurons through its regulation of DMT1. (PMID:19706893)
• PTEN/Akt and MAP kinase signaling pathways are regulated by the ubiquitin ligase activators Ndfip1 and Ndfip2 (PMID:20534535)
• Cellular up-regulation of Nedd4 family interacting protein 1 (Ndfip1) using low levels of bioactive cobalt complexes. (PMID:21187286)
• Ndfip1 negatively regulates RIG-I-dependent immune signaling by enhancing E3 ligase Smurf1-mediated MAVS degradation. (PMID:23087404)
• In Parkinson’s disease, increased iron levels are associated with increased Ndfip1 expression for the regulation of DMT1, including abnormal Ndfip1 activation in non-neuronal cell types such as astrocytes. (PMID:24475238)
• Ndfip1 is required during stress for ubiquitinating and trafficking BRAT1 into the nucleus. (PMID:25631046)
• Silencing of Ndfip1 inhibited cytokine-induced apoptosis of pancreatic islets and promoted glucose-stimulated insulin secretion. These effects were associated with an increase in the cellular content of JunB, a potent inhibitor of ER stress and apoptosis. (PMID:26319551)
• Data show that membrane protein Ndfip1 recruits E3 ubiquitin (Ub) ligase Nedd4-2 to the Golgi to target ether-a-go-go-related gene (hERG) channel for degradation while membrane protein Ndfip2 also mediates Nedd4-2 interaction with hERG in the Golgi. (PMID:26363003)
• the expression of Ndfipl reduced expression of a-synuclein. In conclusion, Ndfipl plays a significant role in protecting SH-SY5Y cells in in vitro Parkinson’s disease models. (PMID:27173227)
• we identified Nedd4-family interacting protein 1 as a direct target of miR-155, and the expression of Nedd4-family interacting protein 1 was inhibited by miR-155. Furthermore, ectopic expression of Nedd4-family interacting protein 1 restored the effects of miR-155 on cell proliferation and invasion of uveal melanoma cells (PMID:29333944)
• We found that in addition to influencing catalytic activities, the WW domain linker regions in NEDD4-1 and WWP2 can impact product distribution, including the degree of polyubiquitination and Lys-48 versus Lys-63 linkages. We show that allosteric activation by NDFIP1 or engineered ubiquitin variants is largely mediated by relief of WW domain linker autoinhibition. (PMID:31578285)
• UBA6 and NDFIP1 regulate the degradation of ferroportin. (PMID:34320783)
• Genetic variation in NDFIP1 modifies the metabolic patterns in immune cells of multiple sclerosis patients. (PMID:34725369)
• Research progress on the role of Ndfip1 (Nedd4 family interacting protein 1) in immune cells. (PMID:36617825)
• NDFIP1 limits cellular TAZ accumulation via exosomal sorting to inhibit NSCLC proliferation. (PMID:36929005)
• Ndfip1 protected dopaminergic neurons via regulating mitochondrial function and ferroptosis in Parkinson’s disease. (PMID:38365133)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ndfip1	ENSDARG00000013979
danio_rerio	ndfip1l	ENSDARG00000102367
mus_musculus	Ndfip1	ENSMUSG00000024425
rattus_norvegicus	Ndfip1	ENSRNOG00000013562
drosophila_melanogaster	Ndfip	FBGN0052177

Paralogs (1): NDFIP2 (ENSG00000102471)

Protein

Protein identifiers

NEDD4 family-interacting protein 1 — Q9BT67 (reviewed: Q9BT67)

Alternative names: Breast cancer-associated protein SGA-1M, NEDD4 WW domain-binding protein 5, Putative MAPK-activating protein PM13, Putative NF-kappa-B-activating protein 164, Putative NFKB and MAPK-activating protein

All UniProt accessions (1): Q9BT67

UniProt curated annotations — full annotation on UniProt →

Function. Activates HECT domain-containing E3 ubiquitin-protein ligases, including NEDD4 and ITCH, and consequently modulates the stability of their targets. As a result, controls many cellular processes. Prevents chronic T-helper cell-mediated inflammation by activating ITCH and thus controlling JUNB degradation. Promotes pancreatic beta cell death through degradation of JUNB and inhibition of the unfolded protein response, leading to reduction of insulin secretion. Restricts the production of pro-inflammatory cytokines in effector Th17 T-cells by promoting ITCH-mediated ubiquitination and degradation of RORC. Together with NDFIP2, limits the cytokine signaling and expansion of effector Th2 T-cells by promoting degradation of JAK1, probably by ITCH- and NEDD4L-mediated ubiquitination. Regulates peripheral T-cell tolerance to self and foreign antigens, forcing the exit of naive CD4+ T-cells from the cell cycle before they become effector T-cells. Negatively regulates RLR-mediated antiviral response by promoting SMURF1-mediated ubiquitination and subsequent degradation of MAVS. Negatively regulates KCNH2 potassium channel activity by decreasing its cell-surface expression and interfering with channel maturation through recruitment of NEDD4L to the Golgi apparatus where it mediates KCNH2 degradation. In cortical neurons, mediates the ubiquitination of the divalent metal transporter SLC11A2/DMT1 by NEDD4L, leading to its down-regulation and protection of the cells from cobalt and iron toxicity. Important for normal development of dendrites and dendritic spines in cortex. Enhances the ubiquitination of BRAT1 mediated by: NEDD4, NEDD4L and ITCH and is required for the nuclear localization of ubiquitinated BRAT1. Enhances the ITCH-mediated ubiquitination of MAP3K7 by recruiting E2 ubiquitin-conjugating enzyme UBE2L3 to ITCH. Modulates EGFR signaling through multiple pathways. In particular, may regulate the ratio of AKT1-to-MAPK8 signaling in response to EGF, acting on AKT1 probably through PTEN destabilization and on MAPK8 through ITCH-dependent MAP2K4 inactivation. As a result, may control cell growth rate. Inhibits cell proliferation by promoting PTEN nuclear localization and changing its signaling specificity.

Subunit / interactions. Forms heterodimers with NDFIP2. Interacts with several E3 ubiquitin-protein ligases, including ITCH, NEDD4, NEDD4L and WWP2. The interaction with NEDD4, NEDD4L and ITCH leads to relocalization of these proteins to exosomes and eventually to exosomal secretion. Interacts with U2SURP. Interacts with SLC11A2/DMT1. Interacts with PTEN. May interact with phosphorylated EGFR. Interacts with BRAT1. Interacts with KCNH2. Interacts with MAVS. Part of a complex containing ITCH, NDFIP1 and MAP3K7. Interacts (via N-terminus) with UBE2L3; the interaction mediates recruitment of UBE2L3 to ITCH.

Subcellular location. Endosome membrane. Golgi apparatus membrane. Synapse. Synaptosome. Cell projection. Dendrite. Secreted.

Tissue specificity. Widely expressed. Higher levels are detected in cerebellum, pituitary, thalamus, kidney, liver, testis, salivary glands and placenta. Also expressed in fetal brain, kidney and lung.

Post-translational modifications. Ubiquitinated by NEDD4 and ITCH; mono-, di- and polyubiquitinated forms are detected. Ubiquitination regulates its degradation. Undergoes transient tyrosine phosphorylation following EGF stimulation, most probably by catalyzed by SRC. Phosphorylation SRC is enhanced in the presence of NDFIP2 which may act as a scaffold to recruit SRC to NDFIP1.

Domain organisation. The PPxY motifs are required for E3 ubiquitin-protein ligase binding and activation and for ubiquitination.

Induction. Increased protein expression in neuronal cells in response to Co(2+) or Fe(2+) ions.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BT67-1	1	yes
Q9BT67-2	2

RefSeq proteins (1): NP_085048* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019325	NEDD4/Bsd2	Family

Pfam: PF10176

UniProt features (23 total): topological domain 4, region of interest 3, short sequence motif 3, mutagenesis site 3, transmembrane region 3, splice variant 2, sequence conflict 2, initiator methionine 1, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BT67-F1	63.27	0.06

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): 2

Mutagenesis-validated functional residues (3):

Position	Phenotype
41–42	loss of phosphorylation; when associated with 66-s-y-67 and 75-s-y-76. greatly decreases nedd4-binding; when associated
66–67	loss of phosphorylation; when associated with 41-p-y-42 and 75-s-y-76. greatly decreases nedd4-binding; when associated
75–76	loss of phosphorylation; when associated with 41-p-y-42 and 66-s-y-67. greatly decreases nedd4-binding; when associated

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 358 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, TAATAAT_MIR126, GOBP_NEGATIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_INFLAMMATORY_RESPONSE, GOBP_B_CELL_ACTIVATION, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, TTTGTAG_MIR520D, GOBP_NEGATIVE_REGULATION_OF_PRODUCTION_OF_MOLECULAR_MEDIATOR_OF_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_MEDIATED_IMMUNITY, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_NEGATIVE_REGULATION_OF_DNA_RECOMBINATION

GO Biological Process (21): regulation of myeloid leukocyte differentiation (GO:0002761), negative regulation of type 2 immune response (GO:0002829), ubiquitin-dependent protein catabolic process (GO:0006511), intracellular iron ion homeostasis (GO:0006879), vacuolar transport (GO:0007034), metal ion transport (GO:0030001), positive regulation of protein ubiquitination (GO:0031398), negative regulation of interleukin-4 production (GO:0032713), CD4-positive, alpha-beta T cell proliferation (GO:0035739), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), regulation of lymphocyte differentiation (GO:0045619), positive regulation of protein catabolic process (GO:0045732), negative regulation of isotype switching to IgE isotypes (GO:0048294), regulation of isotype switching to IgG isotypes (GO:0048302), negative regulation of inflammatory response (GO:0050728), negative regulation of CD4-positive, alpha-beta T cell proliferation (GO:2000562), negative regulation of gene expression (GO:0010629), protein catabolic process (GO:0030163), negative regulation of transporter activity (GO:0032410), negative regulation of protein transport (GO:0051224)

GO Molecular Function (2): WW domain binding (GO:0050699), protein binding (GO:0005515)

GO Cellular Component (14): Golgi membrane (GO:0000139), extracellular region (GO:0005576), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), cell cortex (GO:0005938), endosome membrane (GO:0010008), dendrite (GO:0030425), synapse (GO:0045202), perinuclear region of cytoplasm (GO:0048471), cytoplasm (GO:0005737), endosome (GO:0005768), membrane (GO:0016020), cell projection (GO:0042995), neuron projection (GO:0043005)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cytoplasm	4
endomembrane system	3
regulation of leukocyte differentiation	2
protein ubiquitination	2
bounding membrane of organelle	2
intracellular membrane-bounded organelle	2
myeloid leukocyte differentiation	1
regulation of myeloid cell differentiation	1
regulation of type 2 immune response	1
type 2 immune response	1
negative regulation of immune response	1
modification-dependent protein catabolic process	1
intracellular monoatomic cation homeostasis	1
inorganic ion homeostasis	1
intracellular transport	1
monoatomic cation transport	1
regulation of protein ubiquitination	1
positive regulation of protein modification by small protein conjugation or removal	1
negative regulation of cytokine production	1
interleukin-4 production	1
regulation of interleukin-4 production	1
CD4-positive, alpha-beta T cell activation	1
alpha-beta T cell proliferation	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
lymphocyte differentiation	1
regulation of lymphocyte activation	1
positive regulation of catabolic process	1
protein catabolic process	1
regulation of protein catabolic process	1
positive regulation of protein metabolic process	1
negative regulation of isotype switching	1
isotype switching to IgE isotypes	1
regulation of isotype switching to IgE isotypes	1
regulation of isotype switching	1
isotype switching to IgG isotypes	1

Protein interactions and networks

STRING

931 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NDFIP1	NEDD4	P46934	999
NDFIP1	WWP2	O00308	933
NDFIP1	NEDD4L	Q96PU5	853
NDFIP1	HECW1	Q76N89	823
NDFIP1	SMURF2	Q9HAU4	673
NDFIP1	ITCH	Q96J02	669
NDFIP1	SLC11A2	P49281	649
NDFIP1	SMURF1	Q9HCE7	634
NDFIP1	WWP1	Q9H0M0	576
NDFIP1	PTEN	P60484	555
NDFIP1	SLC11A1	P49279	508
NDFIP1	CBL	P22681	483
NDFIP1	BCAP29	Q9UHQ4	483
NDFIP1	RNF14	Q9UBS8	444
NDFIP1	SLCO6A1	Q86UG4	440

IntAct

115 interactions, top by confidence:

A	B	Type	Score
SLC20A1	LIN7A	psi-mi:“MI:0914”(association)	0.640
SLC12A2	CLGN	psi-mi:“MI:0914”(association)	0.640
UQCRH	NDFIP1	psi-mi:“MI:0915”(physical association)	0.560
MANSC1	KLRG2	psi-mi:“MI:0914”(association)	0.530
TSPAN3	MAP1LC3B2	psi-mi:“MI:0914”(association)	0.530
TGFBR2	PIK3R2	psi-mi:“MI:0914”(association)	0.530
CD83	BTAF1	psi-mi:“MI:0914”(association)	0.530
ARRDC4	WWP2	psi-mi:“MI:0914”(association)	0.530
TPCN2	AP3B1	psi-mi:“MI:0914”(association)	0.530
MRAP2	GOLIM4	psi-mi:“MI:0914”(association)	0.530
STX11	EXOC5	psi-mi:“MI:0914”(association)	0.530
TCIRG1	AP3D1	psi-mi:“MI:0914”(association)	0.530
TEX29	TOR1A	psi-mi:“MI:0914”(association)	0.530
PTGIR	TMEM63A	psi-mi:“MI:0914”(association)	0.530
ENTPD7	PGK2	psi-mi:“MI:0914”(association)	0.530
ARMH4	ELAPOR2	psi-mi:“MI:0914”(association)	0.500
SLC11A2	NDFIP1	psi-mi:“MI:0915”(physical association)	0.400
NDFIP1	SLC11A2	psi-mi:“MI:0915”(physical association)	0.400
NDFIP1	BDKRB1	psi-mi:“MI:0915”(physical association)	0.370
NDFIP1	CCR2	psi-mi:“MI:0915”(physical association)	0.370
NDFIP1	SMO	psi-mi:“MI:0915”(physical association)	0.370
	SNAP23	psi-mi:“MI:0914”(association)	0.350
IZUMO1	CNOT1	psi-mi:“MI:0914”(association)	0.350
RUSF1	MAP1LC3B2	psi-mi:“MI:0914”(association)	0.350
TPCN2	DDX11L8	psi-mi:“MI:0914”(association)	0.350
SLC20A1	MPP2	psi-mi:“MI:0914”(association)	0.350
SLC1A1	TNFRSF10B	psi-mi:“MI:0914”(association)	0.350
MRAP2	GOSR1	psi-mi:“MI:0914”(association)	0.350

BioGRID (178): NDFIP1 (Affinity Capture-MS), NDFIP1 (Affinity Capture-MS), NDFIP1 (Affinity Capture-MS), NDFIP1 (Affinity Capture-MS), NDFIP1 (Affinity Capture-MS), NDFIP1 (Affinity Capture-MS), NDFIP1 (Affinity Capture-MS), NDFIP1 (Affinity Capture-MS), NDFIP1 (Affinity Capture-MS), NDFIP1 (Affinity Capture-MS), NDFIP1 (Affinity Capture-MS), NDFIP1 (Affinity Capture-MS), NDFIP1 (Affinity Capture-MS), NDFIP1 (Affinity Capture-MS), NDFIP1 (Affinity Capture-RNA)

ESM2 similar proteins: A0A1B0GQX3, A0A1B0GRQ0, A0A1B0GVT2, A0A590UK83, A4QNL6, A5D7B5, A6H770, B3DHH5, E1BAR0, O75324, P0DKX4, P35803, P56695, P58511, P61807, P61808, P84889, Q12016, Q15053, Q17Q87, Q28793, Q2TZ20, Q3MHM8, Q4V786, Q4V921, Q4VBG5, Q56JY4, Q5RBD8, Q5U2S1, Q68FV2, Q6DGP4, Q6GLN5, Q758B5, Q80Z96, Q80ZU4, Q876Z1, Q8BH07, Q8BT42, Q8GUM4, Q8R0W6

Diamond homologs: Q4V786, Q5U2S1, Q6DGP4, Q6GLN5, Q8R0W6, Q91ZP6, Q9BT67, Q9NV92

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
NDFIP1	“up-regulates activity”	NEDD4	relocalization
WWP1	“down-regulates quantity”	NDFIP1	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 147 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.

GO biological processes:

GO term	Partners	Fold	FDR
ERAD pathway	7	9.9×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	12
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2108 predictions. Top by Δscore:

Variant	Effect	Δscore
5:142131806:A:AG	acceptor_gain	1.0000
5:142131807:G:GC	acceptor_gain	1.0000
5:142131807:GTT:G	acceptor_gain	1.0000
5:142131892:GCAG:G	donor_gain	1.0000
5:142131896:G:GG	donor_gain	1.0000
5:142131896:G:T	donor_loss	1.0000
5:142131897:T:G	donor_loss	1.0000
5:142132343:G:GG	donor_gain	1.0000
5:142135726:TTAGG:T	acceptor_loss	1.0000
5:142135728:A:AG	acceptor_gain	1.0000
5:142135728:AG:A	acceptor_gain	1.0000
5:142135729:G:GG	acceptor_gain	1.0000
5:142135729:GG:G	acceptor_gain	1.0000
5:142135729:GGAT:G	acceptor_gain	1.0000
5:142135815:TCAG:T	donor_loss	1.0000
5:142135818:G:GG	donor_gain	1.0000
5:142135819:T:A	donor_loss	1.0000
5:142135822:G:GG	donor_gain	1.0000
5:142137732:A:AG	acceptor_gain	1.0000
5:142137732:AGT:A	acceptor_gain	1.0000
5:142137733:G:GG	acceptor_gain	1.0000
5:142137733:GT:G	acceptor_gain	1.0000
5:142137733:GTG:G	acceptor_gain	1.0000
5:142137733:GTGGC:G	acceptor_gain	1.0000
5:142138378:GAGAT:G	donor_gain	1.0000
5:142109034:GCAG:G	donor_gain	0.9900
5:142109035:CAGG:C	donor_loss	0.9900
5:142109036:AGGTA:A	donor_loss	0.9900
5:142109037:GGT:G	donor_loss	0.9900
5:142109039:T:A	donor_loss	0.9900

AlphaMissense

1444 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:142135785:G:A	G113E	1.000
5:142135799:T:C	F118L	1.000
5:142135800:T:C	F118S	1.000
5:142135801:C:A	F118L	1.000
5:142135801:C:G	F118L	1.000
5:142137745:T:A	F128I	1.000
5:142137750:C:A	N129K	1.000
5:142137750:C:G	N129K	1.000
5:142137751:T:A	W130R	1.000
5:142137751:T:C	W130R	1.000
5:142137757:G:A	G132R	1.000
5:142137757:G:C	G132R	1.000
5:142137757:G:T	G132W	1.000
5:142137758:G:A	G132E	1.000
5:142137758:G:T	G132V	1.000
5:142137761:T:C	F133S	1.000
5:142137775:T:C	C138R	1.000
5:142137796:G:A	G145R	1.000
5:142137796:G:C	G145R	1.000
5:142137797:G:A	G145E	1.000
5:142137805:G:A	G148R	1.000
5:142137805:G:C	G148R	1.000
5:142137805:G:T	G148W	1.000
5:142137806:G:A	G148E	1.000
5:142137806:G:T	G148V	1.000
5:142137809:C:A	A149D	1.000
5:142137817:G:A	G152R	1.000
5:142137817:G:C	G152R	1.000
5:142137818:G:A	G152E	1.000
5:142137818:G:T	G152V	1.000

dbSNP variants (sampled 300 via entrez): RS1000025342 (5:142130335 C>G,T), RS1000058864 (5:142123573 T>A), RS1000073140 (5:142139235 G>T), RS1000074737 (5:142130097 C>A,T), RS1000125758 (5:142125008 A>G), RS1000159677 (5:142149371 T>C), RS1000224454 (5:142106990 T>C), RS1000250188 (5:142136586 C>A), RS1000257125 (5:142106810 C>T), RS1000276532 (5:142114130 A>G,T), RS1000344489 (5:142120087 T>C), RS1000435145 (5:142142285 T>C), RS1000443552 (5:142126577 A>G), RS1000597750 (5:142154650 C>G,T), RS1000696617 (5:142113169 A>G)

Disease associations

OMIM: gene MIM:612050 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

47 associations (top):

Study	Trait	p-value
GCST000879_59	Crohn’s disease	2.000000e-09
GCST001198_65	Multiple sclerosis	2.000000e-06
GCST001508_2	Asthma	4.000000e-06
GCST001725_84	Inflammatory bowel disease	4.000000e-14
GCST003987_25	Asthma	3.000000e-08
GCST004131_100	Inflammatory bowel disease	5.000000e-10
GCST004132_114	Crohn’s disease	7.000000e-12
GCST004600_162	Eosinophil percentage of white cells	3.000000e-23
GCST004603_8	Platelet count	3.000000e-17
GCST004606_129	Eosinophil count	1.000000e-34
GCST004607_239	Plateletcrit	1.000000e-29
GCST004613_141	Sum neutrophil eosinophil counts	9.000000e-17
GCST004614_83	Granulocyte count	1.000000e-17
GCST004617_107	Eosinophil percentage of granulocytes	2.000000e-17
GCST004623_11	Neutrophil percentage of granulocytes	2.000000e-16
GCST004624_92	Sum eosinophil basophil counts	1.000000e-35
GCST004750_71	Squamous cell lung carcinoma	6.000000e-06
GCST005038_63	Allergic disease (asthma, hay fever or eczema)	5.000000e-15
GCST005212_36	Asthma	8.000000e-09
GCST005531_40	Multiple sclerosis	4.000000e-09
GCST005537_232	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	2.000000e-09
GCST005991_84	Platelet count	3.000000e-09
GCST006862_4	Asthma	9.000000e-10
GCST007798_29	Asthma	2.000000e-16
GCST007798_30	Asthma	1.000000e-16
GCST007799_19	Asthma (adult onset)	2.000000e-12
GCST007800_79	Asthma (childhood onset)	2.000000e-22
GCST007941_7	Medication use (adrenergics, inhalants)	4.000000e-12
GCST008502_5	Low susceptibility to hepatitis C infection	5.000000e-06
GCST008839_143	Height	2.000000e-07

EFO canonical traits (17, from GWAS)

EFO ID	Trait name
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004309	platelet count
EFO:0004842	eosinophil count
EFO:0007985	platelet crit
EFO:0004833	neutrophil count
EFO:0007987	granulocyte count
EFO:0007996	eosinophil percentage of granulocytes
EFO:0007994	neutrophil percentage of granulocytes
EFO:0005090	basophil count
EFO:1002011	adult onset asthma
EFO:0009941	Inhalant adrenergic use measurement
EFO:0010101	decreased susceptibility to hepatitis C infection
EFO:0005937	longitudinal BMI measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0004527	mean corpuscular hemoglobin
EFO:0007989	monocyte percentage of leukocytes

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
sodium arsenite	increases abundance, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
bisphenol F	affects cotreatment, affects expression	1
methylmercuric chloride	increases expression	1
uranyl acetate	affects expression	1
testosterone undecanoate	affects cotreatment, decreases expression	1
manganese chloride	increases abundance, increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	decreases expression, decreases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
dorsomorphin	increases expression, affects cotreatment	1
bisphenol S	affects cotreatment, increases expression	1
Fulvestrant	increases methylation	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Carbamazepine	affects expression	1
Coumestrol	affects cotreatment, decreases expression	1
Dexamethasone	affects cotreatment, affects expression, increases expression	1
Diethylstilbestrol	decreases expression	1
Indomethacin	affects cotreatment, affects expression, increases expression	1
Manganese	increases abundance, increases expression	1
Dronabinol	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
Uranium	affects expression	1
Urethane	increases expression	1
Valproic Acid	affects expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, affects expression, increases expression	1
1-Methyl-4-phenylpyridinium	affects localization, decreases reaction, decreases expression, increases activity, increases expression	1

Clinical trials (associated diseases)

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