NELFE

Summary

NELFE (negative elongation factor complex member E, HGNC:13974) is a protein-coding gene on chromosome 6p21.33, encoding Negative elongation factor E (P18615). Essential component of the NELF complex, a complex that negatively regulates the elongation of transcription by RNA polymerase II. It is a selective cancer dependency (DepMap: 37.6% of cell lines).

The protein encoded by this gene is part of a complex termed negative elongation factor (NELF) which represses RNA polymerase II transcript elongation. This protein bears similarity to nuclear RNA-binding proteins; however, it has not been demonstrated that this protein binds RNA. The protein contains a tract of alternating basic and acidic residues, largely arginine (R) and aspartic acid (D). The gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6.

Source: NCBI Gene 7936 — RefSeq curated summary.

At a glance

• GWAS associations: 29
• Clinical variants (ClinVar): 70 total
• Cancer dependency (DepMap): dependent in 37.6% of screened cell lines
• MANE Select transcript: NM_002904

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13974
Approved symbol	NELFE
Name	negative elongation factor complex member E
Location	6p21.33
Locus type	gene with protein product
Status	Approved
Aliases	RD, D6S45, NELF-E, RDP
Ensembl gene	ENSG00000204356
Ensembl biotype	protein_coding
OMIM	154040
Entrez	7936

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 18 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay

ENST00000375425, ENST00000375429, ENST00000426722, ENST00000436289, ENST00000441998, ENST00000444811, ENST00000454913, ENST00000481121, ENST00000488426, ENST00000491139, ENST00000492185, ENST00000492539, ENST00000494956, ENST00000625905, ENST00000882598, ENST00000882599, ENST00000882600, ENST00000882601, ENST00000882602, ENST00000882603, ENST00000937367, ENST00000937368, ENST00000948308, ENST00000948309

RefSeq mRNA: 1 — MANE Select: NM_002904 NM_002904

CCDS: CCDS4730

Canonical transcript exons

ENST00000375429 — 11 exons

Exon	Start	End
ENSE00001866940	31952087	31952398
ENSE00001878868	31958892	31958971
ENSE00003490001	31958372	31958454
ENSE00003559714	31955219	31955293
ENSE00003563635	31956693	31956838
ENSE00003609712	31954080	31954134
ENSE00003610398	31956941	31957010
ENSE00003632968	31955059	31955096
ENSE00003638391	31954555	31954892
ENSE00003674045	31953729	31953831
ENSE00003684630	31954298	31954442

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 61.0337 / max 261.5518, expressed in 1827 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
72866	58.9917	1827
72865	1.8937	1278
72864	0.1483	42

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	98.70	gold quality
right testis	UBERON:0004534	98.65	gold quality
testis	UBERON:0000473	97.69	gold quality
right uterine tube	UBERON:0001302	96.78	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.36	gold quality
pituitary gland	UBERON:0000007	96.17	gold quality
adenohypophysis	UBERON:0002196	96.15	gold quality
fallopian tube	UBERON:0003889	96.04	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.02	gold quality
left adrenal gland cortex	UBERON:0035825	95.80	gold quality
left adrenal gland	UBERON:0001234	95.73	gold quality
ventricular zone	UBERON:0003053	95.73	gold quality
right adrenal gland	UBERON:0001233	95.71	gold quality
left coronary artery	UBERON:0001626	95.58	gold quality
substantia nigra	UBERON:0002038	95.57	gold quality
popliteal artery	UBERON:0002250	95.57	gold quality
tibial artery	UBERON:0007610	95.57	gold quality
right adrenal gland cortex	UBERON:0035827	95.55	gold quality
body of pancreas	UBERON:0001150	95.54	gold quality
body of uterus	UBERON:0009853	95.54	gold quality
thoracic aorta	UBERON:0001515	95.53	gold quality
ascending aorta	UBERON:0001496	95.52	gold quality
apex of heart	UBERON:0002098	95.46	gold quality
body of stomach	UBERON:0001161	95.36	gold quality
descending thoracic aorta	UBERON:0002345	95.33	gold quality
metanephros cortex	UBERON:0010533	95.32	gold quality
left ovary	UBERON:0002119	95.30	gold quality
ectocervix	UBERON:0012249	95.27	gold quality
placenta	UBERON:0001987	95.24	gold quality
subcutaneous adipose tissue	UBERON:0002190	95.24	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ENAD-17	no	275.96
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, CAMTA1, FOS, FOXN1, GATA5, JUN, NR1H4, PARP1, ZFPM1

miRNA regulators (miRDB)

23 targeting NELFE, 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-6129	100.00	66.46	2080
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-12135	98.99	70.26	1814
HSA-MIR-6760-5P	98.87	66.73	1515
HSA-MIR-4260	98.78	65.37	848
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-5572	98.55	65.84	970
HSA-MIR-450A-2-3P	97.91	67.56	1459
HSA-MIR-634	97.74	67.11	818
HSA-MIR-4329	97.68	66.26	1003
HSA-MIR-4786-5P	97.45	67.89	924
HSA-MIR-3126-5P	96.87	65.83	912
HSA-MIR-6875-5P	96.87	65.49	958

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 37.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 22)

• Evidence that negative elongation factor represses transcription elongation through binding to a DRB sensitivity-inducing factor/RNA polymerase II complex and RNA (PMID:11940650)
• NELF-C and NELF-D are highly related or identical to the protein called TH1, of unknown function. NELF-B and NELF-C or NELF-D are integral subunits that bring NELF-A and NELF-E together. [NELF-B] [NELF-C] (PMID:12612062)
• 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole sensitivity-inducing factor (DSIF)- and NELF-mediated transcriptional pausing has a dual function in regulating immediate-early expression of the human junB gene. (PMID:16880520)
• NELF E RRM binds to the single-stranded TAR RNAs with K(d) values in the low-micromolar range. (PMID:16898873)
• Negative elongation factor (NELF) is a four subunit transcription factor. Our results point to a surprising role of NELF in the 3’ end processing of histone mRNAs and suggest that NELF is a new factor that coordinates mRNA processing in transcription. (PMID:17499042)
• RNA binding to NELF-E RRM induces formation of a helix in the C-terminus. RNA-bound form of NELF-E RRM is very similar to RNA-bound form of U1A RRM, although C-terminus of NELF-E RRM is unstructured in free protein, whereas it is helical in U1A protein. (PMID:18303858)
• data show that NELF subunits exhibit highly specific subcellular localizations, such as in NELF bodies or in midbodies, and some shuttle actively between the nucleus and cytoplasm; loss of NELF from cells can lead to enlarged and/or multiple nuclei (PMID:19245807)
• Our results do not support any major role of the 4 AMD-associated variants in the risk of developing PCV, but favor a predominant association with the RDBP-SKIV2L variants (PMID:19556007)
• Transient NELF-E knock-down in pituitary increased coincidentally prolactin expression and enhanced transcription of a prolactin-promoter reporter gene. (PMID:20097260)
• Multivariate analysis revealed that RDBP protein levels were an independent risk factor for early intrahepatic recurrence of HCC within 2 years of surgery. (PMID:22614758)
• the transcription elongation of KSHV OriLytL-K7 lytic genes is inhibited by NELF during latency, but can also be promptly reactivated in an RTA-independent manner upon external stimuli (PMID:22740393)
• these results describe the RNA binding behavior of NELF-E and supports a biological role for NELF-E in promoter-proximal pausing of both HIV-1 and cellular genes. (PMID:24453987)
• Following NELF-E knockdown or tumor necrosis factor alpha stimulation, promoter-proximal RNAP II levels increase up to 3-fold, and there is a dramatic increase in RNAP II levels within the HIV genome. (PMID:24636995)
• novel actions of BRD4 and of NELF-E in GR-controlled gene induction have been uncovered. (PMID:26504077)
• A positively charged face of NELF-AC is involved in RNA binding, whereas the opposite face of the NELF-AC subcomplex binds NELF-B. NELF-B is predicted to form a HEAT repeat fold, also binds RNA in vivo, and anchors the subunit NELF-E, which is confirmed to bind RNA in vivo. (PMID:27282391)
• define two mutually exclusive complexes CBC-NELF-E and CBC-ARS2-PHAX, which likely act in respectively earlier and later phases of transcription (PMID:29101316)
• NELFE-Dependent MYC Signature Identifies a Unique Cancer Subtype in Hepatocellular Carcinoma. (PMID:30833661)
• NELFE expression was increased in pancreatic cancer (PC) tissues compared with the paired normal tissues. NELFE expression was upregulated in PC cells when compared with normal pancreatic cells. Knockdown of NELFE inhibited the proliferation, invasion and migration of PC cells. NELFE activates the Wnt/betacatenin signaling pathway and epithelialtomesenchymal transition by decreasing the stabilization of NDRG2 mRNA in PC. (PMID:31638184)
• NELF complex fosters BRCA1 and RAD51 recruitment to DNA damage sites and modulates sensitivity to PARP inhibition. (PMID:33248388)
• Overexpression of NELFE contributes to gastric cancer progression via Wnt/beta-catenin signaling-mediated activation of CSNK2B expression. (PMID:33526068)
• Genome-wide chromatin contacts of super-enhancer-associated lncRNA identify LINC01013 as a regulator of fibrosis in the aortic valve. (PMID:35041643)
• Dependency of NELF-E-SLUG-KAT2B epigenetic axis in breast cancer carcinogenesis. (PMID:37117180)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	nelfe	ENSDARG00000004343
mus_musculus	Nelfe	ENSMUSG00000024369
rattus_norvegicus	Nelfe	ENSRNOG00000000420

Protein

Protein identifiers

Negative elongation factor E — P18615 (reviewed: P18615)

Alternative names: RNA-binding protein RD

All UniProt accessions (8): P18615, A0A0A0MSN9, A0A0A0MT02, A0A1U9X830, A2ABK4, E7ENC7, E7EWR7, E9PD43

UniProt curated annotations — full annotation on UniProt →

Function. Essential component of the NELF complex, a complex that negatively regulates the elongation of transcription by RNA polymerase II. The NELF complex, which acts via an association with the DSIF complex and causes transcriptional pausing, is counteracted by the P-TEFb kinase complex. Provides the strongest RNA binding activity of the NELF complex and may initially recruit the NELF complex to RNA. (Microbial infection) The NELF complex is involved in HIV-1 latency possibly involving recruitment of PCF11 to paused RNA polymerase II.

Subunit / interactions. The NELF complex is composed of NELFA, NELFB, NELFCD (isoform NELF-C or isoform NELF-D) and NELFE. Interacts with NELFB. (Microbial infection) Binds to the HIV-1 TAR RNA which is located in the long terminal repeat (LTR) of HIV-1.

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Widely expressed. Expressed in heart, brain, lung, placenta, liver, skeletal muscle, kidney and pancreas.

Post-translational modifications. Phosphorylated by the P-TEFb complex at sites next to its RNA recognition motif, promoting its release from chromatin. Sumoylated. Poly-ADP-ribosylated by PARP1, thereby preventing RNA-binding and relieving transcription pausing.

Domain organisation. The RRM domain interacts with RNA, and is essential for NELF complex function. It is however not required for the NELF complex formation.

Similarity. Belongs to the RRM NELF-E family.

Isoforms (3)

UniProt ID	Names	Canonical?
P18615-1	1	yes
P18615-3	2
P18615-4	3

RefSeq proteins (1): NP_002895* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR033102	NELFE	Family
IPR034637	NELFE_RRM	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily

Pfam: PF00076

UniProt features (91 total): repeat 30, modified residue 21, mutagenesis site 7, sequence conflict 6, strand 6, turn 4, region of interest 3, compositionally biased region 3, cross-link 3, helix 3, splice variant 2, chain 1, domain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
8UHG	ELECTRON MICROSCOPY	2.7
8UI0	ELECTRON MICROSCOPY	2.7
8JJ6	X-RAY DIFFRACTION	2.72
5OOB	X-RAY DIFFRACTION	2.79
8UHD	ELECTRON MICROSCOPY	2.8
6GML	ELECTRON MICROSCOPY	3.2
9J0O	ELECTRON MICROSCOPY	3.3
9J0P	ELECTRON MICROSCOPY	3.3
9J0N	ELECTRON MICROSCOPY	3.4
8UHA	ELECTRON MICROSCOPY	3.5
8W8E	ELECTRON MICROSCOPY	3.9
7YCX	ELECTRON MICROSCOPY	4.18
1X5P	SOLUTION NMR
2BZ2	SOLUTION NMR
2JX2	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P18615-F1	63.90	0.11

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): 51, 113, 115, 122, 131, 139, 151, 165, 172, 179, 181, 185, 187, 191, 249, 251, 272, 274, 281, 353 …

Mutagenesis-validated functional residues (7):

Position	Phenotype
122	abolished poly-adp-ribosylation by parp1; when associated with q-151; q-172 and q-374.
151	abolished poly-adp-ribosylation by parp1; when associated with q-122; q-172 and q-374.
171	abolished poly-adp-ribosylation by parp1; when associated with q-122; q-151 and q-374.
181–191	decreased phosphorylation.
181–191	mimics phosphorylation, promoting its release from chromatin.
295–299	abolishes interaction with rna but not the interaction with other proteins of the nelf complex.
374	abolished poly-adp-ribosylation by parp1; when associated with q-122; q-151 and q-172.

Function

Pathways and Gene Ontology

Reactome pathways

26 pathways

ID	Pathway
R-HSA-112382	Formation of RNA Pol II elongation complex
R-HSA-113418	Formation of the Early Elongation Complex
R-HSA-167152	Formation of HIV elongation complex in the absence of HIV Tat
R-HSA-167158	Formation of the HIV-1 Early Elongation Complex
R-HSA-167200	Formation of HIV-1 elongation complex containing HIV-1 Tat
R-HSA-167238	Pausing and recovery of Tat-mediated HIV elongation
R-HSA-167242	Abortive elongation of HIV-1 transcript in the absence of Tat
R-HSA-167243	Tat-mediated HIV elongation arrest and recovery
R-HSA-167246	Tat-mediated elongation of the HIV-1 transcript
R-HSA-167287	HIV elongation arrest and recovery
R-HSA-167290	Pausing and recovery of HIV elongation
R-HSA-674695	RNA Polymerase II Pre-transcription Events
R-HSA-6796648	TP53 Regulates Transcription of DNA Repair Genes
R-HSA-75955	RNA Polymerase II Transcription Elongation
R-HSA-162587	HIV Life Cycle
R-HSA-162599	Late Phase of HIV Life Cycle
R-HSA-162906	HIV Infection
R-HSA-1643685	Disease
R-HSA-167169	HIV Transcription Elongation
R-HSA-167172	Transcription of the HIV genome
R-HSA-212436	Generic Transcription Pathway
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-5663205	Infectious disease
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 189 (showing top): GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, PATIL_LIVER_CANCER, REACTOME_HIV_INFECTION, ABE_VEGFA_TARGETS_2HR, BYSTROEM_CORRELATED_WITH_IL5_UP, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, MODULE_98, NOUZOVA_TRETINOIN_AND_H4_ACETYLATION, ZAMORA_NOS2_TARGETS_UP, GOBP_POSITIVE_REGULATION_OF_ERK1_AND_ERK2_CASCADE, HU_GENOTOXIN_ACTION_DIRECT_VS_INDIRECT_24HR, GOBP_NEGATIVE_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_ELONGATION, CAGCCTC_MIR4855P, GOBP_ERK1_AND_ERK2_CASCADE, GOBP_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_ELONGATION

GO Biological Process (7): negative regulation of transcription by RNA polymerase II (GO:0000122), negative regulation of transcription elongation by RNA polymerase II (GO:0034244), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of ERK1 and ERK2 cascade (GO:0070374), transcription pausing by RNA polymerase II (GO:0160239), regulation of DNA-templated transcription (GO:0006355), transcription by RNA polymerase II (GO:0006366)

GO Molecular Function (5): chromatin binding (GO:0003682), RNA binding (GO:0003723), mRNA binding (GO:0003729), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (7): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), plasma membrane (GO:0005886), nuclear body (GO:0016604), NELF complex (GO:0032021), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
Transcription of the HIV genome	6
HIV Transcription Elongation	3
RNA Polymerase II Transcription Elongation	2
RNA Polymerase II Transcription	2
Tat-mediated elongation of the HIV-1 transcript	1
Transcriptional Regulation by TP53	1
HIV Infection	1
HIV Life Cycle	1
Viral Infection Pathways	1
Late Phase of HIV Life Cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	3
binding	3
regulation of transcription by RNA polymerase II	2
DNA-templated transcription	2
cellular anatomical structure	2
intracellular membraneless organelle	2
negative regulation of DNA-templated transcription	1
transcription elongation by RNA polymerase II	1
negative regulation of DNA-templated transcription, elongation	1
regulation of transcription elongation by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
positive regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
RNA biosynthetic process	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
nucleic acid binding	1
RNA binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
membrane	1
cell periphery	1
nucleoplasm	1
transcription elongation factor complex	1

Protein interactions and networks

STRING

2638 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NELFE	NELFB	Q8WX92	999
NELFE	NELFCD	Q8IXH7	999
NELFE	SUPT5H	O00267	960
NELFE	SUPT4H1	P63272	957
NELFE	NELFA	Q9H3P2	949
NELFE	NCBP1	Q09161	857
NELFE	CDK9	P50750	721
NELFE	SKIC2	Q15477	690
NELFE	CBX3	Q13185	675
NELFE	CCNT1	O60563	635
NELFE	MEPCE	Q7L2J0	586
NELFE	LARP7	Q4G0J3	584
NELFE	XRN2	Q9H0D6	582
NELFE	CCNT2	O60583	558
NELFE	LSM2	Q9Y333	537

IntAct

102 interactions, top by confidence:

A	B	Type	Score
NELFE	NELFB	psi-mi:“MI:0915”(physical association)	0.920
NELFA	NELFE	psi-mi:“MI:0915”(physical association)	0.900
NELFA	NELFE	psi-mi:“MI:0914”(association)	0.900
NELFA	NELFE	psi-mi:“MI:0403”(colocalization)	0.900
YWHAB	PIK3C2A	psi-mi:“MI:0914”(association)	0.800
POLR2D	POLR2K	psi-mi:“MI:0915”(physical association)	0.730
FECH	PGRMC1	psi-mi:“MI:0914”(association)	0.700
POLR2C	SUPT5H	psi-mi:“MI:0914”(association)	0.640
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
NELFE	NELFCD	psi-mi:“MI:0914”(association)	0.640
YWHAE	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAZ	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
TRIM27	NELFE	psi-mi:“MI:0915”(physical association)	0.560
NELFE	CCDC57	psi-mi:“MI:0915”(physical association)	0.560
NELFE	MTUS2	psi-mi:“MI:0915”(physical association)	0.560
CCDC57	NELFE	psi-mi:“MI:0915”(physical association)	0.560
NELFE	KANK2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (278): NELFE (Two-hybrid), MTUS2 (Two-hybrid), CCDC57 (Two-hybrid), NELFE (Affinity Capture-MS), NELFA (Affinity Capture-MS), NELFCD (Affinity Capture-MS), NELFB (Affinity Capture-MS), IGHMBP2 (Affinity Capture-MS), DIS3 (Affinity Capture-MS), NELFB (Two-hybrid), NCOR1 (Two-hybrid), CACTIN (Two-hybrid), NELFE (Co-fractionation), NELFE (Co-fractionation), NELFE (Co-fractionation)

ESM2 similar proteins: A1L2F3, A2AG50, A2AUY4, B9DFV2, D3YXK2, D4A666, E1B7L7, E1BUG7, F4IS91, G3CHK5, G3X9Z4, O35691, O60293, O94913, P18615, P61129, Q03173, Q0V9A3, Q14151, Q14241, Q15424, Q4G0F8, Q5F489, Q5HZG4, Q5R452, Q5R5X0, Q5TYQ8, Q5VUA4, Q63187, Q68D10, Q68FG3, Q6DGN6, Q6NU13, Q6P0D5, Q6ZQ03, Q6ZU65, Q80WC1, Q8CB77, Q8IMP6, Q8N3X1

Diamond homologs: P18615, P19426, P31483, P52912, P70318, P92204, Q01085, Q0J9Y2, Q0V898, Q95ZE9, Q9FPJ8, Q9LEB4, Q9V3G3, A2A5N3, A5DM21, A5DW14, F1QB54, F4I3B3, P11940, P20965, P29341, P61286, Q00539, Q0WW84, Q13310, Q28IQ9, Q4VXU2, Q5AI15, Q5R8F7, Q6DEY7, Q6GR16, Q6IP09, Q8BHN5, Q8CFD1, Q8IUH3, Q8R3C6, Q98SP8, Q9EPH8, Q9FXA2, Q9H361

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NELFE	“form complex”	NELF	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 87 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
FGFR2 mutant receptor activation	8	93.7×	1e-13
Abortive elongation of HIV-1 transcript in the absence of Tat	12	91.7×	3e-19
Signaling by FGFR2 IIIa TM	8	74.0×	9e-13
Activation of BAD and translocation to mitochondria	6	70.3×	1e-09
Formation of the Early Elongation Complex	12	62.0×	2e-17
Formation of the HIV-1 Early Elongation Complex	12	62.0×	2e-17
HIV Transcription Elongation	12	62.0×	2e-17
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	6	62.0×	3e-09

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	23.8×	4e-04
positive regulation of transcription elongation by RNA polymerase II	5	19.5×	8e-04
RNA splicing	9	10.3×	1e-04
mRNA splicing, via spliceosome	8	9.5×	4e-04
intracellular protein localization	7	9.5×	1e-03
transcription by RNA polymerase II	7	6.4×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	50
Likely benign	6
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1169 predictions. Top by Δscore:

Variant	Effect	Δscore
6:31952395:ACAG:A	acceptor_gain	1.0000
6:31952396:CAG:C	acceptor_gain	1.0000
6:31952396:CAGC:C	acceptor_gain	1.0000
6:31952397:AG:A	acceptor_gain	1.0000
6:31952398:GC:G	acceptor_loss	1.0000
6:31952399:C:CC	acceptor_gain	1.0000
6:31953724:CTTAC:C	donor_loss	1.0000
6:31953725:TTACC:T	donor_loss	1.0000
6:31953726:TACCG:T	donor_loss	1.0000
6:31953727:A:AC	donor_gain	1.0000
6:31953727:A:T	donor_loss	1.0000
6:31953728:C:CC	donor_gain	1.0000
6:31953751:G:A	donor_gain	1.0000
6:31953829:GAG:G	acceptor_gain	1.0000
6:31953832:C:CC	acceptor_gain	1.0000
6:31953839:A:T	acceptor_gain	1.0000
6:31954002:T:TA	donor_gain	1.0000
6:31954132:CAG:C	acceptor_gain	1.0000
6:31954291:T:TA	donor_gain	1.0000
6:31954296:A:AC	donor_gain	1.0000
6:31954297:C:CC	donor_gain	1.0000
6:31954297:CTTT:C	donor_gain	1.0000
6:31954553:A:AC	donor_gain	1.0000
6:31954554:C:CC	donor_gain	1.0000
6:31955213:CTTTA:C	donor_loss	1.0000
6:31955214:TTTAC:T	donor_loss	1.0000
6:31955215:TTACC:T	donor_loss	1.0000
6:31955216:TAC:T	donor_loss	1.0000
6:31955217:AC:A	donor_loss	1.0000
6:31955218:C:A	donor_loss	1.0000

AlphaMissense

2466 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:31953785:G:T	A330D	1.000
6:31953794:A:T	V327D	1.000
6:31954091:C:G	A311P	1.000
6:31954123:A:T	V300D	1.000
6:31954125:G:C	F299L	1.000
6:31954125:G:T	F299L	1.000
6:31954126:A:C	F299C	1.000
6:31954126:A:G	F299S	1.000
6:31954127:A:G	F299L	1.000
6:31954129:G:T	A298D	1.000
6:31954334:C:A	G284V	1.000
6:31954334:C:T	G284E	1.000
6:31953739:C:A	W345C	0.999
6:31953739:C:G	W345C	0.999
6:31953741:A:G	W345R	0.999
6:31953741:A:T	W345R	0.999
6:31953830:A:G	L315P	0.999
6:31954090:G:T	A311D	0.999
6:31954099:G:T	A308E	0.999
6:31954118:A:C	Y302D	0.999
6:31954127:A:T	F299I	0.999
6:31954130:C:G	A298P	0.999
6:31954319:A:G	L289P	0.999
6:31954335:C:G	G284R	0.999
6:31954335:C:T	G284R	0.999
6:31954345:G:C	F280L	0.999
6:31954345:G:T	F280L	0.999
6:31954346:A:G	F280S	0.999
6:31954347:A:G	F280L	0.999
6:31954358:A:G	L276P	0.999

dbSNP variants (sampled 300 via entrez): RS1000946917 (6:31952413 G>A,C,T), RS1001073605 (6:31959803 C>A,T), RS1002735312 (6:31953285 G>T), RS1003248402 (6:31957432 C>G), RS1004032075 (6:31956075 C>A,T), RS1004941054 (6:31956401 T>G), RS1004974933 (6:31955004 G>A,C), RS1005695627 (6:31954344 A>C), RS1005845088 (6:31951659 A>C,G), RS1005862514 (6:31959640 T>C), RS1006144217 (6:31960156 G>C), RS1007321043 (6:31959054 C>G), RS1007818272 (6:31953029 C>A,T), RS1008234137 (6:31955777 G>T), RS1008386719 (6:31956076 G>A)

Disease associations

OMIM: gene MIM:154040 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

29 associations (top):

Study	Trait	p-value
GCST001942_21	Prostate cancer	5.000000e-09
GCST001986_2	Age-related macular degeneration	2.000000e-10
GCST001987_3	Age-related macular degeneration (extreme sampling)	3.000000e-07
GCST004131_25	Inflammatory bowel disease	2.000000e-31
GCST004133_79	Ulcerative colitis	5.000000e-65
GCST004521_114	Autism spectrum disorder or schizophrenia	3.000000e-17
GCST004521_117	Autism spectrum disorder or schizophrenia	3.000000e-15
GCST004521_118	Autism spectrum disorder or schizophrenia	3.000000e-15
GCST004521_126	Autism spectrum disorder or schizophrenia	2.000000e-10
GCST004521_154	Autism spectrum disorder or schizophrenia	3.000000e-08
GCST004521_162	Autism spectrum disorder or schizophrenia	3.000000e-08
GCST004521_17	Autism spectrum disorder or schizophrenia	2.000000e-12
GCST004521_173	Autism spectrum disorder or schizophrenia	4.000000e-14
GCST004521_209	Autism spectrum disorder or schizophrenia	5.000000e-16
GCST004521_211	Autism spectrum disorder or schizophrenia	5.000000e-15
GCST004521_213	Autism spectrum disorder or schizophrenia	5.000000e-13
GCST004521_224	Autism spectrum disorder or schizophrenia	5.000000e-10
GCST004521_227	Autism spectrum disorder or schizophrenia	4.000000e-12
GCST004521_296	Autism spectrum disorder or schizophrenia	6.000000e-18
GCST004521_45	Autism spectrum disorder or schizophrenia	2.000000e-16
GCST004521_81	Autism spectrum disorder or schizophrenia	1.000000e-14
GCST005196_95	Coronary artery disease	6.000000e-13
GCST005359_2	Disease progression in age-related macular degeneration	8.000000e-10
GCST007446_6	vWF levels	3.000000e-08
GCST008916_30	Asthma	1.000000e-09
GCST012227_771	Hip circumference adjusted for BMI	2.000000e-23
GCST90020024_1062	A body shape index	5.000000e-17
GCST90020025_521	Waist-to-hip ratio adjusted for BMI	1.000000e-14
GCST90020027_768	Waist-hip index	2.000000e-13

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0008336	disease progression measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
cobaltous chloride	decreases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, increases oxidation	1
bisphenol A	decreases expression	1
tetrahydropalmatine	decreases expression	1
tetrabromobisphenol A	decreases expression	1
coumarin	increases phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	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
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Acetaminophen	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Arsenic	affects methylation	1
Benzo(a)pyrene	decreases methylation	1
Caffeine	decreases phosphorylation	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Ivermectin	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A5U4	SEES3-1V human RDBP, clone1	Embryonic stem cell	Male
CVCL_A5U5	SEES3-1V human RDBP, clone2	Embryonic stem cell	Male
CVCL_A5U6	SEES3-1V human RDBP, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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