NELFA

Summary

NELFA (negative elongation factor complex member A, HGNC:12768) is a protein-coding gene on chromosome 4p16.3, encoding Negative elongation factor A (Q9H3P2). 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 93.4% of cancer cell lines).

This gene is expressed ubiquitously with higher levels in fetal than in adult tissues. It encodes a protein sharing 93% sequence identity with the mouse protein. Wolf-Hirschhorn syndrome (WHS) is a malformation syndrome associated with a hemizygous deletion of the distal short arm of chromosome 4. This gene is mapped to the 165 kb WHS critical region, and may play a role in the phenotype of the WHS or Pitt-Rogers-Danks syndrome. The encoded protein is found to be capable of reacting with HLA-A2-restricted and tumor-specific cytotoxic T lymphocytes, suggesting a target for use in specific immunotherapy for a large number of cancer patients. This protein has also been shown to be a member of the NELF (negative elongation factor) protein complex that participates in the regulation of RNA polymerase II transcription elongation.

Source: NCBI Gene 7469 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 128 total
• Phenotypes (HPO): 95
• Cancer dependency (DepMap): dependent in 93.4% of screened cell lines (common-essential)
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_005663

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12768
Approved symbol	NELFA
Name	negative elongation factor complex member A
Location	4p16.3
Locus type	gene with protein product
Status	Approved
Aliases	NELF-A
Ensembl gene	ENSG00000185049
Ensembl biotype	protein_coding
OMIM	606026
Entrez	7469

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 14 protein_coding, 4 nonsense_mediated_decay, 4 retained_intron

ENST00000333877, ENST00000382882, ENST00000411649, ENST00000416258, ENST00000421397, ENST00000431323, ENST00000443203, ENST00000453740, ENST00000455762, ENST00000458616, ENST00000463820, ENST00000467661, ENST00000484545, ENST00000488452, ENST00000542778, ENST00000898320, ENST00000898321, ENST00000898322, ENST00000911416, ENST00000967101, ENST00000967102, ENST00000967103

RefSeq mRNA: 1 — MANE Select: NM_005663 NM_005663

CCDS: CCDS3358

Canonical transcript exons

ENST00000382882 — 11 exons

Exon	Start	End
ENSE00001298196	2008750	2008974
ENSE00001898534	1982723	1983503
ENSE00003478080	1985776	1985864
ENSE00003502103	1986272	1986402
ENSE00003515122	1987918	1988007
ENSE00003581129	1983848	1984113
ENSE00003619648	1983596	1983695
ENSE00003730719	1989708	1989869
ENSE00003757928	1991544	1991715
ENSE00003785976	1986114	1986183
ENSE00003788935	1984808	1984919

Expression profiles

Bgee: expression breadth ubiquitous, 276 present calls, max score 94.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.2932 / max 142.7503, expressed in 1800 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
51098	23.5221	1798
51099	0.4107	205
51100	0.3605	156

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	94.74	gold quality
secondary oocyte	CL:0000655	94.50	gold quality
lower esophagus mucosa	UBERON:0035834	93.80	gold quality
right uterine tube	UBERON:0001302	93.02	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.43	gold quality
mucosa of transverse colon	UBERON:0004991	92.14	gold quality
right testis	UBERON:0004534	91.86	gold quality
left testis	UBERON:0004533	91.85	gold quality
left ovary	UBERON:0002119	91.82	gold quality
cerebellar hemisphere	UBERON:0002245	91.77	gold quality
cerebellar cortex	UBERON:0002129	91.62	gold quality
esophagus mucosa	UBERON:0002469	91.62	gold quality
skin of leg	UBERON:0001511	91.35	gold quality
right ovary	UBERON:0002118	91.25	gold quality
ventricular zone	UBERON:0003053	91.18	gold quality
skin of abdomen	UBERON:0001416	91.06	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.90	gold quality
vagina	UBERON:0000996	90.79	gold quality
adenohypophysis	UBERON:0002196	90.72	gold quality
testis	UBERON:0000473	90.70	gold quality
metanephros cortex	UBERON:0010533	90.43	gold quality
minor salivary gland	UBERON:0001830	90.31	gold quality
ectocervix	UBERON:0012249	90.27	gold quality
right lobe of thyroid gland	UBERON:0001119	90.26	gold quality
endocervix	UBERON:0000458	90.24	gold quality
transverse colon	UBERON:0001157	90.23	gold quality
cerebellum	UBERON:0002037	90.13	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.03	gold quality
right frontal lobe	UBERON:0002810	89.90	gold quality
sural nerve	UBERON:0015488	89.90	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-124858	no	17.22
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

35 targeting NELFA, 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-4262	100.00	73.26	3931
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-4692	100.00	67.32	2066
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-1284	99.67	73.56	1353
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-377-3P	99.37	70.18	1905
HSA-MIR-133A-3P	99.27	71.53	1270
HSA-MIR-133B	99.27	71.53	1270

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 93.4% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 10)

• 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)
• connection between the syndrome phenotype and cytogenetic abnormalities, through gradual shortening of the length of the critical region WHSCR (finally up to 165 kb), and sequencing it, at least 2 genes (WHSC1 and WHSC2) were identified. (PMID:12715353)
• 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)
• 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)
• haploinsufficiency of SLBP and/or WHSC2 (NELF-A) contributes to several novel cellular phenotypes of WHS. (PMID:22328085)
• 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)
• 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)
• The noncoding function of NELFA mRNA promotes the development of oesophageal squamous cell carcinoma by regulating the Rad17-RFC2-5 complex. (PMID:31845510)
• Stress-induced nuclear condensation of NELF drives transcriptional downregulation. (PMID:33548202)
• ERK-mediated NELF-A phosphorylation promotes transcription elongation of immediate-early genes by releasing promoter-proximal pausing of RNA polymerase II. (PMID:36463234)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nelfa	ENSDARG00000061411
mus_musculus	Nelfa	ENSMUSG00000029111
rattus_norvegicus	Nelfa	ENSRNOG00000015474
drosophila_melanogaster	Nelf-A	FBGN0038872

Protein

Protein identifiers

Negative elongation factor A — Q9H3P2 (reviewed: Q9H3P2)

Alternative names: Wolf-Hirschhorn syndrome candidate 2 protein

All UniProt accessions (11): Q9H3P2, A0A0C4DFX9, C9JEM7, C9JHL4, F8W954, F8WF98, H0Y3X6, H7C0W2, H7C2C7, H7C2M8, H7C3C2

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. (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; NELFA and NELFCD form a stable subcomplex that binds to the N-terminus of NELFB. In vitro, the NELFA:NELFCD subcomplex binds to ssDNA and ssRNA in a sequence- and structure-dependent manner. Interacts with the RNA polymerase II complex when it is not phosphorylated by P-TEFb.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitous. Expressed in heart, brain, placenta, liver, skeletal muscle, kidney and pancreas. Expressed at lower level in adult lung. Expressed in fetal brain, lung, liver and kidney.

Domain organisation. The HDAg-like domain is essential for transcriptional repression, and mediates the interaction with the RNA polymerase II complex.

Similarity. Belongs to the NELF-A family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H3P2-1	1	yes
Q9H3P2-7	2

RefSeq proteins (1): NP_005654* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR037517	HDAG_dom	Domain
IPR052828	NELF-A_domain	Family
IPR056557	NELF-A_N	Domain

Pfam: PF23553

UniProt features (35 total): helix 12, modified residue 5, turn 4, region of interest 4, sequence conflict 2, strand 2, compositionally biased region 2, chain 1, domain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
8UHG	ELECTRON MICROSCOPY	2.7
8UI0	ELECTRON MICROSCOPY	2.7
5L3X	X-RAY DIFFRACTION	2.75
8UHD	ELECTRON MICROSCOPY	2.8
6GML	ELECTRON MICROSCOPY	3.2
8UIS	ELECTRON MICROSCOPY	3.23
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-Q9H3P2-F1	69.23	0.43

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 (5): 233, 277, 363, 157, 225

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: 401 (showing top): GGGACCA_MIR133A_MIR133B, SHEPARD_BMYB_MORPHOLINO_UP, GGGNRMNNYCAT_UNKNOWN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, MORF_HDAC2, BROWNE_HCMV_INFECTION_24HR_UP, FONTAINE_PAPILLARY_THYROID_CARCINOMA_UP, REACTOME_HIV_INFECTION, WATANABE_RECTAL_CANCER_RADIOTHERAPY_RESPONSIVE_UP, MODULE_379, BLALOCK_ALZHEIMERS_DISEASE_UP, TGTGTGA_MIR377, chr4p16, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN

GO Biological Process (2): negative regulation of transcription elongation by RNA polymerase II (GO:0034244), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (3): chromatin binding (GO:0003682), molecular adaptor activity (GO:0060090), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), nuclear body (GO:0016604), NELF complex (GO:0032021)

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
binding	3
cellular anatomical structure	2
transcription elongation by RNA polymerase II	1
negative regulation of DNA-templated transcription, elongation	1
regulation of transcription elongation by RNA polymerase II	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
molecular_function	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
nucleoplasm	1
intracellular membraneless organelle	1
transcription elongation factor complex	1

Protein interactions and networks

STRING

1438 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NELFA	NELFB	Q8WX92	956
NELFA	NELFCD	Q8IXH7	953
NELFA	NELFE	P18615	949
NELFA	SUPT5H	O00267	878
NELFA	SUPT4H1	P63272	866
NELFA	ACAT1	P24752	704
NELFA	LETM1	O95202	671
NELFA	NSD2	O96028	640
NELFA	CDC42	P21181	616
NELFA	RHOA	P06749	591
NELFA	SRF	P11831	583
NELFA	DSE	Q9UL01	542
NELFA	PIGG	Q5H8A4	524
NELFA	HDAC4	P56524	506
NELFA	TOP2A	P11388	497

IntAct

127 interactions, top by confidence:

A	B	Type	Score
NELFCD	NELFA	psi-mi:“MI:0915”(physical association)	0.900
NELFA	NELFE	psi-mi:“MI:0915”(physical association)	0.900
NELFA	NELFCD	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
NELFA	NELFCD	psi-mi:“MI:0915”(physical association)	0.740
POLR2D	POLR2K	psi-mi:“MI:0915”(physical association)	0.730
POLR2C	SUPT5H	psi-mi:“MI:0914”(association)	0.640
NELFE	NELFCD	psi-mi:“MI:0914”(association)	0.640
NELFA	SUPT5H	psi-mi:“MI:0914”(association)	0.640
YWHAB	BLTP3B	psi-mi:“MI:0914”(association)	0.610
NELFA	SIAH1	psi-mi:“MI:0915”(physical association)	0.560
NELFA		psi-mi:“MI:0915”(physical association)	0.560
	NELFA	psi-mi:“MI:0915”(physical association)	0.560
PIN1	NELFA	psi-mi:“MI:0915”(physical association)	0.560
CDK3	NELFA	psi-mi:“MI:0915”(physical association)	0.560
MLH1	NELFA	psi-mi:“MI:0915”(physical association)	0.560
SMARCD1	NELFA	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (144): NELFA (Two-hybrid), NELFCD (Two-hybrid), PRR22 (Two-hybrid), NELFA (Affinity Capture-RNA), NELFA (Affinity Capture-MS), NELFA (Affinity Capture-MS), POLR2A (Affinity Capture-MS), POLR2B (Affinity Capture-MS), POLR2C (Affinity Capture-MS), SUPT5H (Affinity Capture-MS), NELFA (Affinity Capture-MS), NELFA (Affinity Capture-MS), NELFA (Affinity Capture-MS), NELFE (Affinity Capture-MS), NELFB (Affinity Capture-MS)

ESM2 similar proteins: A0A7P0TBJ1, A0A804C8T0, A2BE76, A2RRV3, A4IG66, A4IIE8, D4A4K3, O75182, P57095, P97578, Q02225, Q08AY9, Q09YG9, Q09YK4, Q1JPG0, Q28C41, Q2IBF8, Q2QL82, Q2QLF8, Q2QLG9, Q4QQM5, Q503U3, Q5BLE2, Q5M836, Q5XJS0, Q62141, Q62671, Q68EF0, Q6DFB7, Q6GR21, Q6NRB7, Q6P7D5, Q6PCG6, Q7L4E1, Q86YS3, Q8BG30, Q8BHS8, Q8BK03, Q8BQP8, Q8NAN2

Diamond homologs: Q86NP2, Q8BG30, Q9H3P2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NELFA	“form complex”	NELF	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 113 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	110.2×	5e-20
Abortive elongation of HIV-1 transcript in the absence of Tat	14	91.5×	5e-23
Signaling by FGFR2 IIIa TM	11	87.0×	1e-18
FGFR2 alternative splicing	12	66.8×	2e-18
HIV Transcription Elongation	15	66.3×	3e-22
MicroRNA (miRNA) biogenesis	11	66.1×	5e-17
Signaling by FGFR2	12	64.4×	3e-18
Pausing and recovery of Tat-mediated HIV elongation	13	63.0×	2e-19

GO biological processes:

GO term	Partners	Fold	FDR
alternative mRNA splicing, via spliceosome	5	34.8×	1e-04
mRNA transport	5	13.6×	7e-03
mRNA splicing, via spliceosome	9	8.5×	3e-04
transcription by RNA polymerase II	11	8.0×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	73
Likely benign	36
Benign	8

Top pathogenic / likely-pathogenic (0)

SpliceAI

2475 predictions. Top by Δscore:

Variant	Effect	Δscore
4:1983500:TTCT:T	acceptor_gain	1.0000
4:1983502:CT:C	acceptor_gain	1.0000
4:1983504:C:CC	acceptor_gain	1.0000
4:1983591:CATA:C	donor_loss	1.0000
4:1983592:ATAC:A	donor_loss	1.0000
4:1983593:TACCT:T	donor_loss	1.0000
4:1983594:A:AC	donor_gain	1.0000
4:1983594:AC:A	donor_gain	1.0000
4:1983594:ACCTC:A	donor_loss	1.0000
4:1983595:C:CA	donor_gain	1.0000
4:1983595:CC:C	donor_gain	1.0000
4:1983595:CCT:C	donor_gain	1.0000
4:1983692:CTCT:C	acceptor_gain	1.0000
4:1983694:CT:C	acceptor_gain	1.0000
4:1983696:C:CC	acceptor_gain	1.0000
4:1983697:T:C	acceptor_loss	1.0000
4:1983700:A:T	acceptor_gain	1.0000
4:1983702:C:CT	acceptor_gain	1.0000
4:1983843:CCTA:C	donor_loss	1.0000
4:1983844:CTAC:C	donor_loss	1.0000
4:1983846:ACCGT:A	donor_loss	1.0000
4:1983847:C:A	donor_loss	1.0000
4:1984109:TGGGG:T	acceptor_gain	1.0000
4:1984110:GGGG:G	acceptor_gain	1.0000
4:1984113:GCTGC:G	acceptor_loss	1.0000
4:1984114:C:CC	acceptor_gain	1.0000
4:1984114:CTGC:C	acceptor_loss	1.0000
4:1984302:AGG:A	donor_gain	1.0000
4:1984917:TTTCT:T	acceptor_loss	1.0000
4:1984919:TC:T	acceptor_loss	1.0000

AlphaMissense

3409 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:1983383:A:C	M508R	1.000
4:1983383:A:G	M508T	1.000
4:1983383:A:T	M508K	1.000
4:1983388:A:C	F506L	1.000
4:1983388:A:T	F506L	1.000
4:1983389:A:G	F506S	1.000
4:1983390:A:G	F506L	1.000
4:1983461:A:G	L482P	1.000
4:1983461:A:T	L482Q	1.000
4:1983607:G:T	A464D	1.000
4:1983608:C:G	A464P	1.000
4:1983610:A:G	M463T	1.000
4:1983612:G:C	F462L	1.000
4:1983612:G:T	F462L	1.000
4:1983613:A:C	F462C	1.000
4:1983613:A:G	F462S	1.000
4:1983614:A:C	F462V	1.000
4:1983614:A:G	F462L	1.000
4:1983614:A:T	F462I	1.000
4:1983619:A:G	L460P	1.000
4:1983619:A:T	L460Q	1.000
4:1983622:A:C	I459S	1.000
4:1983622:A:G	I459T	1.000
4:1983622:A:T	I459N	1.000
4:1983625:A:G	L458P	1.000
4:1983630:C:A	K456N	1.000
4:1983630:C:G	K456N	1.000
4:1983632:T:C	K456E	1.000
4:1983646:A:T	V451D	1.000
4:1983655:G:T	A448D	1.000

dbSNP variants (sampled 300 via entrez): RS1000028762 (4:2000581 C>T), RS1000061386 (4:2000983 T>C,G), RS1000092412 (4:1993852 G>A,C), RS1000094265 (4:2006329 T>G), RS1000161060 (4:2009586 G>A), RS1000167731 (4:1994664 G>C,T), RS1000238964 (4:2009432 C>T), RS1000256445 (4:2006063 G>A), RS1000287725 (4:1984428 G>A), RS1000374646 (4:1989429 G>A), RS1000483565 (4:1984653 A>C), RS1000526659 (4:1993519 C>T), RS1000571713 (4:2010551 C>G), RS1000762087 (4:1990618 G>A,C), RS1000848247 (4:1999728 C>T)

Disease associations

OMIM: gene MIM:606026 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

95 total (30 of 95 shown, HPO-id order):

HPO	Term
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000077	Abnormality of the kidney
HP:0000078	Abnormality of the genital system
HP:0000079	Abnormality of the urinary system
HP:0000151	Aplasia of the uterus
HP:0000153	Abnormality of the mouth
HP:0000159	Abnormal lip morphology
HP:0000175	Cleft palate
HP:0000204	Cleft upper lip
HP:0000252	Microcephaly
HP:0000268	Dolichocephaly
HP:0000286	Epicanthus
HP:0000288	Abnormality of the philtrum
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000389	Chronic otitis media
HP:0000431	Wide nasal bridge
HP:0000485	Megalocornea
HP:0000486	Strabismus
HP:0000488	Retinopathy
HP:0000494	Downslanted palpebral fissures
HP:0000501	Glaucoma
HP:0000508	Ptosis
HP:0000520	Proptosis
HP:0000612	Iris coloboma

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

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases reaction, increases abundance, increases expression, affects cotreatment, decreases methylation (+1 more)	3
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	2
Acrolein	affects cotreatment, increases oxidation, increases abundance	2
Benzo(a)pyrene	affects methylation, decreases methylation	2
Dexamethasone	increases expression, affects cotreatment	2
Ozone	affects cotreatment, increases oxidation, increases abundance	2
Valproic Acid	affects expression, increases methylation	2
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
ginger extract	decreases expression, decreases reaction, increases abundance	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
beta-lapachone	decreases expression, increases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
coumarin	increases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	decreases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Sunitinib	increases expression	1
Fulvestrant	decreases methylation, affects cotreatment	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Arsenic	affects methylation	1
Cadmium	increases expression	1
Caffeine	decreases phosphorylation	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Indomethacin	increases expression, affects cotreatment	1
Ivermectin	decreases expression	1
Methapyrilene	decreases methylation	1
Oils, Volatile	decreases expression, decreases reaction, increases abundance	1

Cellosaurus cell lines

4 cell lines: 3 embryonic stem cell, 1 telomerase immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A7V1	SEES3-1V human WHSC2, clone1	Embryonic stem cell	Male
CVCL_A7V2	SEES3-1V human WHSC2, clone2	Embryonic stem cell	Male
CVCL_A7V3	SEES3-1V human WHSC2, clone3	Embryonic stem cell	Male
CVCL_C3L0	N/Tert-1 WHSC2	Telomerase immortalized cell line	Male

Clinical trials (associated diseases)

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