NELFB

Summary

NELFB (negative elongation factor complex member B, HGNC:24324) is a protein-coding gene on chromosome 9q34.3, encoding Negative elongation factor B (Q8WX92). Essential component of the NELF complex, a complex that negatively regulates the elongation of transcription by RNA polymerase II. It is a common-essential gene (DepMap: required in 97.0% of cancer cell lines).

NELFB is a subunit of negative elongation factor (NELF), which also includes NELFA (WHSC2; MIM 606026), either NELFC or NELFD (TH1L; MIM 605297), and NELFE (RDBP; MIM 154040). NELF acts with DRB sensitivity-inducing factor (DSIF), a heterodimer of SPT4 (SUPT4H1; MIM 603555) and SPT5 (SUPT5H; MIM 602102), to cause transcriptional pausing of RNA polymerase II (see MIM 180660) (Narita et al., 2003 [PubMed 12612062]).

Source: NCBI Gene 25920 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 100 total
• Cancer dependency (DepMap): dependent in 97.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_015456

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24324
Approved symbol	NELFB
Name	negative elongation factor complex member B
Location	9q34.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1182, NELF-B
Ensembl gene	ENSG00000188986
Ensembl biotype	protein_coding
OMIM	611180
Entrez	25920

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000343053

RefSeq mRNA: 1 — MANE Select: NM_015456 NM_015456

CCDS: CCDS7040

Canonical transcript exons

ENST00000343053 — 13 exons

Exon	Start	End
ENSE00001367711	137256824	137257054
ENSE00001369681	137256329	137256428
ENSE00001370606	137266944	137267086
ENSE00001374840	137264245	137264357
ENSE00001375311	137272081	137272222
ENSE00001376133	137263037	137263222
ENSE00001379723	137255907	137256070
ENSE00001382884	137267240	137267346
ENSE00001385640	137272507	137272615
ENSE00001386498	137266331	137266426
ENSE00001386804	137255327	137255611
ENSE00001391595	137265877	137265979
ENSE00001412347	137272782	137273542

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 94.77.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.0900 / max 342.1206, expressed in 1806 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
99690	18.5190	1806
99689	0.5710	301

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	94.77	gold quality
ventricular zone	UBERON:0003053	94.40	gold quality
right frontal lobe	UBERON:0002810	93.75	gold quality
lower esophagus mucosa	UBERON:0035834	93.60	gold quality
mucosa of transverse colon	UBERON:0004991	93.12	gold quality
cingulate cortex	UBERON:0003027	93.04	gold quality
ganglionic eminence	UBERON:0004023	92.96	gold quality
anterior cingulate cortex	UBERON:0009835	92.96	gold quality
amygdala	UBERON:0001876	92.95	gold quality
endometrium epithelium	UBERON:0004811	92.88	gold quality
tendon of biceps brachii	UBERON:0008188	92.82	gold quality
stromal cell of endometrium	CL:0002255	92.75	gold quality
skin of leg	UBERON:0001511	92.65	gold quality
cortical plate	UBERON:0005343	92.51	gold quality
granulocyte	CL:0000094	92.26	gold quality
gastrocnemius	UBERON:0001388	92.09	gold quality
nucleus accumbens	UBERON:0001882	92.09	gold quality
skin of abdomen	UBERON:0001416	91.83	gold quality
right coronary artery	UBERON:0001625	91.65	gold quality
prefrontal cortex	UBERON:0000451	91.62	gold quality
body of stomach	UBERON:0001161	91.52	gold quality
transverse colon	UBERON:0001157	91.51	gold quality
muscle of leg	UBERON:0001383	91.42	gold quality
ascending aorta	UBERON:0001496	91.37	gold quality
thoracic aorta	UBERON:0001515	91.36	gold quality
lower esophagus	UBERON:0013473	91.30	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.29	gold quality
aorta	UBERON:0000947	91.28	gold quality
putamen	UBERON:0001874	91.28	gold quality
popliteal artery	UBERON:0002250	91.27	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.92

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
LEF1	Activation
TFF1	Repression

Upstream regulators (CollecTRI, top): ESR1

miRNA regulators (miRDB)

18 targeting NELFB, 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-1193	100.00	65.93	529
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-324-3P	99.26	66.31	1034
HSA-MIR-6829-5P	98.86	65.12	1480
HSA-MIR-6827-5P	98.46	64.88	1256
HSA-MIR-3173-5P	97.35	65.82	1282
HSA-MIR-6799-3P	97.35	65.60	1302
HSA-MIR-874-5P	96.93	63.92	1014
HSA-MIR-6762-5P	96.55	64.62	972
HSA-MIR-6845-5P	96.55	64.65	969
HSA-MIR-541-3P	96.07	66.11	1271
HSA-MIR-654-5P	96.07	66.18	1280
HSA-MIR-7976	95.75	65.67	1186
HSA-MIR-874-3P	95.02	65.66	806
HSA-MIR-10396A-3P	93.99	62.06	94
HSA-MIR-10396B-3P	93.99	62.06	94

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 97.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 17)

• 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)
• differentially expressed in breast cancer cell lines, antibody to it may be a useful tool to investigate its functions (PMID:15185750)
• COBRA1 may directly modulate AP-1 pathway and, therefore, may play important roles in cell proliferation, differentiation, apoptosis, and oncogenesis. (PMID:15530430)
• COBRA1 can negatively regulate the activator protein-1 (AP-1) complex at the TFF1 promoter and thus down-regulate TFF1 expression in gastric cancer cell lines. (PMID:16452188)
• Decreasing NELF also correlated with displacement of a positioned nucleosome and increased acetylation of histone H4, suggesting coupling of transcription elongation and chromatin remodeling (PMID:17442680)
• 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)
• COBRA1 may coordinate multiple steps in ligand-dependent gene expression, which in turn ensures both the quantity and quality of hormone-stimulated gene products (PMID:17659869)
• a lack of COBRA1 expression in breast carcinoma may serve as a useful indicator for poor prognosis. (PMID:17910036)
• COBRA1 and BRCA1 may engage in common gene regulatory pathways to suppress breast cancer progression. (PMID:18071589)
• 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)
• These studies allow us to position the actions of two new modulators of GR-regulated transactivation, NELF-A and NELF-B, relative to other factors in the overall gene induction sequence. (PMID:24097989)
• both human and mouse NELF-B proteins are translated from a non-AUG codon upstream of the annotated AUG. (PMID:26010750)
• 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)
• High COBRA1 expression is associated with hepatocellular carcinoma. (PMID:28112367)
• BRCA1 Interacting Protein COBRA1 Facilitates Adaptation to Castrate-Resistant Growth Conditions. (PMID:30036938)
• NSUN6, an RNA methyltransferase of 5-mC controls glioblastoma response to temozolomide (TMZ) via NELFB and RPS6KB2 interaction. (PMID:34705606)
• Structural basis of the human negative elongation factor NELF-B/C/E ternary complex. (PMID:37591184)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nelfb	ENSDARG00000035505
mus_musculus	Nelfb	ENSMUSG00000013465
rattus_norvegicus	Nelfb	ENSRNOG00000009377
drosophila_melanogaster	NELF-B	FBGN0027553

Protein

Protein identifiers

Negative elongation factor B — Q8WX92 (reviewed: Q8WX92)

Alternative names: Cofactor of BRCA1

All UniProt accessions (2): A0A5H1ZRP4, Q8WX92

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. May be able to induce chromatin unfolding. Essential for early embryogenesis; plays an important role in maintaining the undifferentiated state of embryonic stem cells (ESCs) by preventing unscheduled expression of developmental genes. Plays a key role in establishing the responsiveness of stem cells to developmental cues; facilitates plasticity and cell fate commitment in ESCs by establishing the appropriate expression level of signaling molecules. Supports the transcription of genes involved in energy metabolism in cardiomyocytes; facilitates the association of transcription initiation factors with the promoters of the metabolism-related genes. (Microbial infection) The NELF complex is involved in HIV-1 latency possibly involving recruitment of PCF11 to paused RNA polymerase II. In vitro, binds weakly to the HIV-1 TAR RNA which is located in the long terminal repeat (LTR) of HIV-1.

Subunit / interactions. The NELF complex is composed of NELFA, NELFB, NELFCD (isoform NELF-C or isoform NELF-D) and NELFE; the N-terminus of NELFB binds to the NELFA:NELFCD subcomplex. Binds RNA which may help to stabilize the NELF complex on nucleic acid. Interacts with the first BRCT repeat of BRCA1. Interacts with KIAA1191. Interacts with NELFE.

Subcellular location. Nucleus.

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

Miscellaneous. Produced by alternative initiation at a CTG start codon.

Similarity. Belongs to the NELF-B family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8WX92-1	1	yes
Q8WX92-2	2

RefSeq proteins (1): NP_056271* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010405	COBRA1	Family

Pfam: PF06209

UniProt features (54 total): helix 38, turn 6, strand 3, modified residue 2, sequence conflict 2, chain 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
8UHG	ELECTRON MICROSCOPY	2.7
8UI0	ELECTRON MICROSCOPY	2.7
8JJ6	X-RAY DIFFRACTION	2.72
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
7PKS	ELECTRON MICROSCOPY	3.6
8W8E	ELECTRON MICROSCOPY	3.9
8RBX	ELECTRON MICROSCOPY	4.1
7YCX	ELECTRON MICROSCOPY	4.18
9VD9	ELECTRON MICROSCOPY	4.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WX92-F1	89.66	0.73

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 (2): 519, 557

Function

Pathways and Gene Ontology

Reactome pathways

31 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-9603505	NTRK3 as a dependence receptor
R-HSA-162582	Signal Transduction
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-166520	Signaling by NTRKs
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-9006934	Signaling by Receptor Tyrosine Kinases
R-HSA-9034015	Signaling by NTRK3 (TRKC)

MSigDB gene sets: 154 (showing top): MODULE_255, GOBP_NEGATIVE_REGULATION_OF_STEM_CELL_DIFFERENTIATION, MODULE_317, MORF_RAF1, REACTOME_HIV_INFECTION, MORF_FANCG, GATA1_01, AIYAR_COBRA1_TARGETS_DN, GATA2_01, GOBP_NEGATIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS, MORF_IKBKG, MORF_AATF, GOBP_STEM_CELL_DIFFERENTIATION, PUJANA_BREAST_CANCER_LIT_INT_NETWORK, YAMAZAKI_TCEB3_TARGETS_DN

GO Biological Process (5): cell population proliferation (GO:0008283), negative regulation of transcription elongation by RNA polymerase II (GO:0034244), stem cell differentiation (GO:0048863), negative regulation of stem cell differentiation (GO:2000737), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (2): RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), NELF complex (GO:0032021)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
Transcription of the HIV genome	5
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
Signaling by NTRK3 (TRKC)	1
HIV Infection	1
HIV Life Cycle	1
Viral Infection Pathways	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cellular process	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
cell differentiation	1
negative regulation of cell differentiation	1
stem cell differentiation	1
regulation of stem cell differentiation	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
nucleic acid binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
transcription elongation factor complex	1

Protein interactions and networks

STRING

1366 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NELFB	NELFE	P18615	999
NELFB	NELFCD	Q8IXH7	999
NELFB	NELFA	Q9H3P2	956
NELFB	SUPT5H	O00267	950
NELFB	SUPT4H1	P63272	926
NELFB	NCBP1	Q09161	772
NELFB	BRCA1	P38398	745
NELFB	ACAT1	P24752	725
NELFB	ESR1	P03372	719
NELFB	INTS11	Q5TA45	666
NELFB	INTS6	Q9UL03	550
NELFB	CDK9	P50750	507
NELFB	ZNF350	Q9GZX5	499
NELFB	AR	P10275	498
NELFB	RSPRY1	Q96DX4	492

IntAct

129 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
NELFA	NELFCD	psi-mi:“MI:0914”(association)	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
YWHAB	BLTP3B	psi-mi:“MI:0914”(association)	0.610
BRCA1	NELFB	psi-mi:“MI:0915”(physical association)	0.600
NELFB	BRCA1	psi-mi:“MI:0403”(colocalization)	0.600
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
YWHAG	SHTN1	psi-mi:“MI:0914”(association)	0.560
NELFE	IGHMBP2	psi-mi:“MI:0914”(association)	0.530
NELFA	IGHMBP2	psi-mi:“MI:0914”(association)	0.530
POLR2I	SUPT5H	psi-mi:“MI:0914”(association)	0.530
POLR2J	SUPT5H	psi-mi:“MI:0914”(association)	0.530

BioGRID (166): NELFB (Affinity Capture-MS), NELFB (Two-hybrid), NELFB (Co-fractionation), NELFB (Affinity Capture-MS), NELFB (Two-hybrid), NELFB (Affinity Capture-MS), NELFB (Affinity Capture-MS), NELFB (Affinity Capture-MS), NELFB (Affinity Capture-MS), NELFB (Affinity Capture-MS), NELFB (Affinity Capture-MS), NELFB (Affinity Capture-MS), NELFB (Affinity Capture-MS), NELFB (Affinity Capture-MS), JUN (Affinity Capture-Western)

ESM2 similar proteins: A0JP85, A1A5H6, A5GFY4, A5YKK6, B0I564, B1AY13, E9Q8I9, O75448, O88480, P21359, P86409, P97526, Q04690, Q0KK59, Q16X15, Q24134, Q29S00, Q2PW47, Q3UHQ6, Q4QQS3, Q4V8B3, Q5F3M0, Q5FWU8, Q5RFA0, Q5TBA9, Q5U249, Q642P2, Q6AXZ5, Q6P4S8, Q6PI53, Q6ZQ08, Q80X82, Q80YV3, Q8BHW2, Q8BL99, Q8C4Y3, Q8IXH7, Q8K368, Q8N201, Q8WX92

Diamond homologs: Q8C4Y3, Q8WX92, Q9Y113

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NELFB	“form complex”	NELF	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 108 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	11	102.1×	9e-20
Abortive elongation of HIV-1 transcript in the absence of Tat	15	90.8×	6e-25
Signaling by FGFR2 IIIa TM	11	80.6×	3e-18
HIV Transcription Elongation	16	65.5×	8e-24
Pausing and recovery of Tat-mediated HIV elongation	14	62.9×	6e-21
Tat-mediated HIV elongation arrest and recovery	14	62.9×	6e-21
Formation of the Early Elongation Complex	15	61.4×	5e-22
Formation of the HIV-1 Early Elongation Complex	15	61.4×	5e-22

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	19.1×	3e-03
epidermal growth factor receptor signaling pathway	5	12.9×	8e-03
intracellular protein localization	7	7.6×	8e-03
transcription by RNA polymerase II	10	7.3×	9e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	79
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2055 predictions. Top by Δscore:

Variant	Effect	Δscore
9:137255906:GACA:G	acceptor_gain	1.0000
9:137256051:G:GT	donor_gain	1.0000
9:137256056:G:GT	donor_gain	1.0000
9:137256056:G:T	donor_gain	1.0000
9:137256060:GC:G	donor_gain	1.0000
9:137256067:A:T	donor_gain	1.0000
9:137256070:GGTG:G	donor_loss	1.0000
9:137256071:G:T	donor_loss	1.0000
9:137256072:T:A	donor_loss	1.0000
9:137256426:AAGGT:A	donor_loss	1.0000
9:137256428:GGTA:G	donor_loss	1.0000
9:137256429:GTAG:G	donor_loss	1.0000
9:137256430:T:A	donor_loss	1.0000
9:137256821:TAG:T	acceptor_loss	1.0000
9:137256822:A:AG	acceptor_gain	1.0000
9:137256822:AGG:A	acceptor_loss	1.0000
9:137256823:G:GG	acceptor_gain	1.0000
9:137256975:A:T	donor_gain	1.0000
9:137256990:G:GG	donor_gain	1.0000
9:137257051:CGAG:C	donor_loss	1.0000
9:137257052:GAGGT:G	donor_loss	1.0000
9:137257053:AG:A	donor_loss	1.0000
9:137257054:GG:G	donor_loss	1.0000
9:137257055:G:GA	donor_loss	1.0000
9:137257056:T:A	donor_loss	1.0000
9:137263032:TGCA:T	acceptor_loss	1.0000
9:137263033:GCAG:G	acceptor_loss	1.0000
9:137263035:A:AG	acceptor_gain	1.0000
9:137263035:AG:A	acceptor_gain	1.0000
9:137263035:AGGT:A	acceptor_gain	1.0000

AlphaMissense

4068 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000113326 (9:137268223 T>C), RS1000226346 (9:137263908 C>T), RS1000287829 (9:137262902 G>A), RS1000305288 (9:137266890 T>A,G), RS1000378331 (9:137273157 C>T), RS1000500844 (9:137258277 C>T), RS1000577371 (9:137269042 C>T), RS1000942528 (9:137253731 C>G), RS1000952112 (9:137253537 G>A,C,T), RS1000965596 (9:137265204 A>G), RS1000975614 (9:137258433 AT>A,ATT), RS1000996973 (9:137264840 G>A), RS1001032894 (9:137258634 T>C), RS1001123383 (9:137259338 C>G,T), RS1001318073 (9:137262406 A>G)

Disease associations

OMIM: gene MIM:611180 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	increases reaction, affects binding, affects reaction	3
sodium arsenite	increases expression	2
bisphenol AF	affects binding, affects folding, increases reaction, decreases reaction	2
Arsenic	affects methylation, decreases methylation	2
FR900359	increases phosphorylation	1
2,4,6-tribromophenol	increases expression	1
bisphenol A	increases reaction, affects binding, affects folding	1
sodium arsenate	decreases expression	1
decabromobiphenyl ether	increases expression	1
tetrabromobisphenol A	increases expression	1
coumarin	increases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
pentabrominated diphenyl ether 100	increases expression	1
bisphenol S	affects binding, decreases reaction	1
LDN 193189	affects cotreatment, increases expression	1
MT19c compound	decreases expression	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Rotenone	decreases expression	1
Smoke	decreases expression	1
Tamoxifen	affects binding, decreases reaction	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases methylation	1
Metribolone	affects binding, affects folding, decreases reaction	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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