NELFCD

Summary

NELFCD (negative elongation factor complex member C/D, HGNC:15934) is a protein-coding gene on chromosome 20q13.32, encoding Negative elongation factor C/D (Q8IXH7). 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: 68.0% of cell lines).

The NELF complex of proteins interacts with the DSIF protein complex to repress transcriptional elongation by RNA polymerase II. The protein encoded by this gene is an essential part of the NELF complex. Alternative translation initiation site usage results in the formation of two isoforms with different N-termini.

Source: NCBI Gene 51497 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 73 total
• Cancer dependency (DepMap): dependent in 68.0% of screened cell lines
• MANE Select transcript: NM_198976

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15934
Approved symbol	NELFCD
Name	negative elongation factor complex member C/D
Location	20q13.32
Locus type	gene with protein product
Status	Approved
Aliases	HSPC130, TH1, NELF-C, NELF-D
Ensembl gene	ENSG00000101158
Ensembl biotype	protein_coding
OMIM	605297
Entrez	51497

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 16 protein_coding, 9 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000460601, ENST00000464363, ENST00000471621, ENST00000474543, ENST00000477741, ENST00000478389, ENST00000479207, ENST00000482747, ENST00000486263, ENST00000490205, ENST00000492016, ENST00000497935, ENST00000602795, ENST00000652272, ENST00000905230, ENST00000905231, ENST00000905232, ENST00000905233, ENST00000905234, ENST00000905235, ENST00000905236, ENST00000905237, ENST00000905238, ENST00000905239, ENST00000915030, ENST00000915031, ENST00000958299, ENST00000958300

RefSeq mRNA: 1 — MANE Select: NM_198976 NM_198976

CCDS: CCDS13473

Canonical transcript exons

ENST00000652272 — 15 exons

Exon	Start	End
ENSE00003471435	58991881	58992020
ENSE00003492669	58986754	58986863
ENSE00003500569	58988914	58989021
ENSE00003517211	58989488	58989640
ENSE00003578931	58987708	58987817
ENSE00003610145	58992998	58993112
ENSE00003612218	58986093	58986208
ENSE00003628522	58994642	58995113
ENSE00003630395	58990910	58991075
ENSE00003663789	58989858	58989988
ENSE00003671950	58991312	58991446
ENSE00003674803	58993449	58993544
ENSE00003692550	58994110	58994239
ENSE00003731241	58993624	58993764
ENSE00003846642	58981256	58981369

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 97.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.9174 / max 187.0301, expressed in 1813 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
185589	32.8925	1813
185590	0.0249	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adenohypophysis	UBERON:0002196	97.43	gold quality
pituitary gland	UBERON:0000007	97.41	gold quality
ventricular zone	UBERON:0003053	97.28	gold quality
ganglionic eminence	UBERON:0004023	96.86	gold quality
right lobe of thyroid gland	UBERON:0001119	96.76	gold quality
left lobe of thyroid gland	UBERON:0001120	96.70	gold quality
embryo	UBERON:0000922	96.64	gold quality
left ovary	UBERON:0002119	96.52	gold quality
thyroid gland	UBERON:0002046	96.21	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.20	gold quality
right ovary	UBERON:0002118	96.19	gold quality
cerebellar hemisphere	UBERON:0002245	96.15	gold quality
islet of Langerhans	UBERON:0000006	96.11	gold quality
cerebellar cortex	UBERON:0002129	96.07	gold quality
right uterine tube	UBERON:0001302	95.99	gold quality
body of uterus	UBERON:0009853	95.74	gold quality
granulocyte	CL:0000094	95.71	gold quality
endocervix	UBERON:0000458	95.61	gold quality
cerebellum	UBERON:0002037	95.50	gold quality
metanephros cortex	UBERON:0010533	95.49	gold quality
right adrenal gland cortex	UBERON:0035827	95.29	gold quality
right adrenal gland	UBERON:0001233	95.28	gold quality
ectocervix	UBERON:0012249	95.21	gold quality
cortical plate	UBERON:0005343	95.19	gold quality
left adrenal gland	UBERON:0001234	95.14	gold quality
skin of abdomen	UBERON:0001416	95.10	gold quality
left uterine tube	UBERON:0001303	95.07	gold quality
esophagus mucosa	UBERON:0002469	95.03	gold quality
left adrenal gland cortex	UBERON:0035825	95.01	gold quality
minor salivary gland	UBERON:0001830	95.00	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7606	no	1475.25
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
CCND1	Repression
CDKN1A	Activation
CTNNB1	Repression

Upstream regulators (CollecTRI, top): AR, TBX21

miRNA regulators (miRDB)

17 targeting NELFCD, 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-3692-3P	99.98	70.27	2139
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-3199	99.17	65.19	696
HSA-MIR-8052	99.17	65.01	719
HSA-MIR-922	99.02	67.23	1838
HSA-MIR-887-5P	98.82	65.90	1347
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-1304-3P	98.29	66.44	1207
HSA-MIR-5681A	97.99	67.17	1658
HSA-MIR-4275	97.96	68.42	1549
HSA-MIR-6781-3P	97.44	66.85	970
HSA-MIR-3121-5P	97.30	66.62	1146
HSA-MIR-2682-3P	97.10	66.16	840
HSA-MIR-6834-5P	96.25	64.88	823

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 68.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 16)

• In a two-hybrid screen of human fetal liver cDNA library, TH1 was detected as a new interaction partner of A-Raf; this specific interaction may have played a critical role in the activation of A-Raf. (PMID:11952167)
• 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)
• Trihydrophobin 1 negatively regulates A-Raf kinase (PMID:14684750)
• A study was done of ubiquitin-dependent proeolysis of TH1L protein by E6-AP. (PMID:17131388)
• 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)
• Maternal serum Th1 cytokines concentrations increase in preterm and term delivery. (PMID:17621989)
• TH1 interacts with PAK1 and specifically restricts the activation of MAPK modules through the upstream region of the MAPK pathway, thereby influencing cell migration. (PMID:19136554)
• 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)
• diverse transcriptional consequence of NELF-mediated RNAPII pausing in the human genome (PMID:20028984)
• These results indicate that TH1 is a novel regulator to control the duration and magnitude of androgen signal transduction and might be directly involved in androgen-related developmental, physiological, and pathological processes. (PMID:20069563)
• TH1 might play an important role in regulation of proliferation and invasion in human breast cancer. (PMID:20735431)
• Trihydrophobin 1 phosphorylation by c-Src regulates MAPK/ERK signaling and cell migration. (PMID:22238675)
• 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)
• NELFCD polymorphisms are associated with jaundice-stage progression in primary biliary cholangitis. (PMID:29795304)
• Structural basis of the human negative elongation factor NELF-B/C/E ternary complex. (PMID:37591184)
• TH1L involvement in colorectal cancer pathogenesis by regulation of CCL20 through the NF-kappaB signalling pathway. (PMID:38809918)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nelfcd	ENSDARG00000021097
mus_musculus	Nelfcd	ENSMUSG00000016253
rattus_norvegicus	Nelfcd	ENSRNOG00000047874
drosophila_melanogaster	TH1	FBGN0010416

Protein

Protein identifiers

Negative elongation factor C/D — Q8IXH7 (reviewed: Q8IXH7)

Alternative names: TH1-like protein

All UniProt accessions (3): Q8IXH7, H0UI80, X6RLT1

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 primarily through NELFCD to the N-terminus of NELFB. Binds RNA which may help to stabilize the NELF complex on nucleic acid. In vitro, the NELFA:NELFCD subcomplex binds to ssDNA and ssRNA in a sequence- and structure-dependent manner. Interacts with ARAF. Interacts with PCF11. Interacts with KAT8.

Subcellular location. Nucleus.

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

Miscellaneous. Produced by alternative initiation at Met-10 of isoform NELF-C.

Similarity. Belongs to the NELF-D family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8IXH7-1	NELF-C	yes
Q8IXH7-3	3
Q8IXH7-4	NELF-D

RefSeq proteins (1): NP_945327* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006942	TH1	Family

Pfam: PF04858

UniProt features (72 total): helix 36, strand 14, mutagenesis site 9, sequence conflict 5, splice variant 3, turn 2, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

16 structures.

PDB	Method	Resolution (Å)
8UHG	ELECTRON MICROSCOPY	2.7
8UI0	ELECTRON MICROSCOPY	2.7
8JJ6	X-RAY DIFFRACTION	2.72
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-Q8IXH7-F1	86.74	0.60

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (9):

Position	Phenotype
374	reduces rna binding; when associated with q-291, m-315, m-371, m-372, m-384, m-388, q-419 and q-506.
384	reduces rna binding; when associated with q-291, m-315, m-371, m-372, m-374, m-388, q-419 and q-506.
388	reduces rna binding; when associated with q-291, m-315, m-371, m-372, m-374, m-384, q-419 and q-506.
419	reduces rna binding; when associated with q-291, m-315, m-371, m-372, m-374, m-384, m-388 and q-506.
506	reduces rna binding; when associated with q-291, m-315, m-371, m-372, m-374, m-384, m-388 and q-419.
291	reduces rna binding; when associated with m-315, m-371, m-372, m-374, m-384, m-388, q-419 and q-506.
315	reduces rna binding; when associated with q-291, m-371, m-372, m-374, m-384, m-388, q-419 and q-506.
371	reduces rna binding; when associated with q-291, m-315, m-372, m-374, m-384, m-388, q-419 and q-506.
372	reduces rna binding; when associated with q-291, m-315, m-371, m-374, m-384, m-388, q-419 and q-506.

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: 138 (showing top): MODULE_255, MODULE_317, REACTOME_HIV_INFECTION, GOBP_NEGATIVE_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_ELONGATION, GOBP_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_ELONGATION, GOCC_NUCLEAR_BODY, GOCC_TRANSCRIPTION_ELONGATION_FACTOR_COMPLEX, GOMF_ENZYME_INHIBITOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, VECCHI_GASTRIC_CANCER_EARLY_UP, NIKOLSKY_BREAST_CANCER_20Q12_Q13_AMPLICON, GOBP_DNA_TEMPLATED_TRANSCRIPTION_ELONGATION, KRIGE_RESPONSE_TO_TOSEDOSTAT_6HR_DN, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, WAKABAYASHI_ADIPOGENESIS_PPARG_BOUND_8D

GO Biological Process (2): negative regulation of transcription elongation by RNA polymerase II (GO:0034244), 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), membrane (GO:0016020), 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
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
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
transcription elongation factor complex	1

Protein interactions and networks

STRING

2339 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NELFCD	NELFB	Q8WX92	999
NELFCD	NELFE	P18615	999
NELFCD	NELFA	Q9H3P2	953
NELFCD	SUPT4H1	P63272	926
NELFCD	SUPT5H	O00267	881
NELFCD	NCBP1	Q09161	799
NELFCD	IFNG	P01579	721
NELFCD	CD4	P01730	693
NELFCD	IL4	P05112	666
NELFCD	IL10	P22301	661
NELFCD	IL2	P01585	658
NELFCD	CD8A	P01732	620
NELFCD	TNF	P01375	620
NELFCD	IL17A	Q16552	590
NELFCD	IL6	P05231	584

IntAct

87 interactions, top by confidence:

A	B	Type	Score
NELFCD	NELFA	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	NELFCD	psi-mi:“MI:0914”(association)	0.900
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
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
NELFCD		psi-mi:“MI:0915”(physical association)	0.560
NELFCD	NELFB	psi-mi:“MI:0915”(physical association)	0.560
	NELFCD	psi-mi:“MI:0915”(physical association)	0.560
KLF11	NELFCD	psi-mi:“MI:0915”(physical association)	0.560
NUP58	NELFCD	psi-mi:“MI:0915”(physical association)	0.560
NELFCD	SPRED1	psi-mi:“MI:0915”(physical association)	0.560
ARAF	NELFCD	psi-mi:“MI:0915”(physical association)	0.550
NELFCD	ARAF	psi-mi:“MI:0915”(physical association)	0.550

BioGRID (156): NELFCD (Two-hybrid), NELFCD (Affinity Capture-MS), NELFCD (Affinity Capture-MS), NELFCD (Synthetic Growth Defect), NELFCD (Affinity Capture-MS), NELFCD (Affinity Capture-MS), NELFCD (Affinity Capture-MS), NELFCD (Affinity Capture-MS), NELFCD (Affinity Capture-MS), NELFCD (Affinity Capture-MS), NELFCD (Affinity Capture-MS), NELFCD (Affinity Capture-MS), NELFCD (Affinity Capture-MS), NELFCD (Affinity Capture-MS), NELFCD (Affinity Capture-MS)

ESM2 similar proteins: A0JP85, A1A5H6, A2AGH6, A5GFY4, A5YKK6, B1AY13, B4KJ11, E9Q8I9, O75448, O94915, O95155, P55824, Q0KK59, Q23658, Q24134, Q2PW47, Q2QCI8, Q4V8B3, Q5F3M0, Q5RCU2, Q5RFA0, Q5TBA9, Q60PC0, Q6GLR7, Q6GYQ0, Q6PI53, Q6ZQ08, Q7ZYV9, Q80TJ1, Q80X82, Q80YV3, Q8BHR2, Q8BL99, Q8IXH7, Q8R0Z2, Q8R1A4, Q922L6, Q92797, Q93074, Q96N67

Diamond homologs: A5GFY4, Q24134, Q5RFA0, Q8IXH7, Q922L6

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
NELFCD	“form complex”	NELF	binding
UBE3A	“down-regulates quantity by destabilization”	NELFCD	ubiquitination
SRC	“down-regulates activity”	NELFCD	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 69 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
Abortive elongation of HIV-1 transcript in the absence of Tat	10	92.0×	1e-15
FGFR2 mutant receptor activation	6	84.6×	9e-10
Signaling by FGFR2 IIIa TM	6	66.8×	4e-09
Formation of the Early Elongation Complex	10	62.2×	4e-14
Formation of the HIV-1 Early Elongation Complex	10	62.2×	4e-14
HIV Transcription Elongation	10	62.2×	4e-14
Pausing and recovery of Tat-mediated HIV elongation	9	61.4×	7e-13
Tat-mediated HIV elongation arrest and recovery	9	61.4×	7e-13

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	53
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2812 predictions. Top by Δscore:

Variant	Effect	Δscore
20:58981368:AGGT:A	donor_loss	1.0000
20:58981370:G:T	donor_loss	1.0000
20:58981371:T:G	donor_loss	1.0000
20:58986081:A:AG	acceptor_gain	1.0000
20:58986082:T:G	acceptor_gain	1.0000
20:58986085:A:AG	acceptor_gain	1.0000
20:58986087:CAACA:C	acceptor_loss	1.0000
20:58986088:AACAG:A	acceptor_loss	1.0000
20:58986089:ACAGC:A	acceptor_loss	1.0000
20:58986091:A:AG	acceptor_gain	1.0000
20:58986091:AG:A	acceptor_loss	1.0000
20:58986092:G:GT	acceptor_gain	1.0000
20:58986204:AAGAG:A	donor_gain	1.0000
20:58986205:AGAG:A	donor_gain	1.0000
20:58986206:GAG:G	donor_gain	1.0000
20:58986206:GAGG:G	donor_gain	1.0000
20:58986209:GTAT:G	donor_gain	1.0000
20:58987705:CAG:C	acceptor_loss	1.0000
20:58987706:A:AG	acceptor_gain	1.0000
20:58987706:A:G	acceptor_loss	1.0000
20:58987706:AG:A	acceptor_gain	1.0000
20:58987707:G:GG	acceptor_gain	1.0000
20:58987707:GG:G	acceptor_gain	1.0000
20:58987707:GGT:G	acceptor_gain	1.0000
20:58987707:GGTGT:G	acceptor_gain	1.0000
20:58987814:A:T	donor_gain	1.0000
20:58987814:AGAGG:A	donor_loss	1.0000
20:58987815:GAG:G	donor_gain	1.0000
20:58987816:AGGT:A	donor_loss	1.0000
20:58987817:GGT:G	donor_loss	1.0000

AlphaMissense

3834 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000192574 (20:58982732 A>G,T), RS1000431225 (20:58985021 T>C), RS1000937329 (20:58985576 G>A), RS1000944399 (20:58990186 C>G,T), RS1001012695 (20:58980167 C>G,T), RS1001107340 (20:58980635 G>C,T), RS1001127079 (20:58980483 T>C), RS1001389545 (20:58985367 G>A), RS1001523023 (20:58986303 A>G), RS1001793977 (20:58982386 G>T), RS1001844087 (20:58993204 G>A,T), RS1002000711 (20:58986526 G>A), RS1002008241 (20:58981118 C>A,G,T), RS1002059236 (20:58980563 T>G), RS1002598934 (20:58983285 C>G,T)

Disease associations

OMIM: gene MIM:605297 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002067_1	Response to diuretic therapy in hypertension	6.000000e-08
GCST004599_214	Mean platelet volume	8.000000e-27
GCST004616_155	Platelet distribution width	6.000000e-27
GCST90002395_605	Mean platelet volume	1.000000e-22

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007984	platelet component distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2273359	Efficacy	3	diuretics;hydrochlorothiazide;Thiazides;plain	Hypertension

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2273359	NELFCD	3	0.00	1	diuretics;hydrochlorothiazide;Thiazides;plain

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, decreases expression	2
Valproic Acid	affects expression, decreases expression	2
2,4,6-tribromophenol	decreases expression	1
decabromobiphenyl ether	decreases expression	1
tetrabromobisphenol A	decreases expression	1
manganese chloride	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
ICG 001	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	decreases expression, increases abundance, affects cotreatment	1
Carbamazepine	affects expression	1
Ivermectin	decreases expression	1
Lead	affects expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Methylcholanthrene	affects binding, increases reaction	1
Plant Extracts	affects cotreatment, increases expression	1
Smoke	increases abundance, increases expression	1
Thiram	decreases expression	1
tert-Butylhydroperoxide	decreases expression	1

Clinical trials (associated diseases)

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