NELFE

protein-coding

negative elongation factor complex member E, the group of RNA binding motif containing|MicroRNA protein coding host genes|Negative elongation factor complex members

Gene summary

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. [provided by RefSeq, Jul 2008]

Previous symbols:

RDBP

MANE transcript

NM_002904.6

Inheritance

—

ClinVar variants

U:57B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.32

Max pathogenic AF

—

Genomic locus

chr6:31,952,087-31,959,038

External References & Databases

Ensembl (ENSG00000204356)

Transcript & Mutation Effects

hg38 • Region Span ~7.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NELFE variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 52

not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002904.6. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	1 clinvar		2
missense			52 clinvar	3 clinvar		55
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	57	4	0	61

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 45 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002904.6	RefSeq	NP_002895.3	10	MANE Select
ENST00000375429.8	Ensembl	ENSP00000364578.3	10	MANE Select
ENST00000375425.10	Ensembl	ENSP00000364574.5	11	Standard
ENST00000375425.9	Ensembl	ENSP00000364574.5	11	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
nelfe	Danio rerio	Structure: hematopoietic multipotent progenitor cell Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

nelfe

Danio rerio

Structure: hematopoietic multipotent progenitor cell

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Initiation of transcription and translation elongation at the HIV-1 LTR
Disease
Formation of the HIV-1 Early Elongation Complex
Gene expression (Transcription)
Formation of HIV-1 elongation complex containing HIV-1 Tat

Biological Process

transcription by RNA polymerase II
transcription elongation from RNA polymerase II promoter
negative regulation of transcription elongation from RNA polymerase II promoter
positive regulation of transcription by RNA polymerase II
positive regulation of histone H3-K4 methylation

Molecular Function

chromatin binding
RNA binding
protein binding

Cellular Component

nucleus
nucleoplasm
plasma membrane
nuclear body
NELF complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000375429
Coding exons: 10
Length: 7024
Individuals with no LoFs: 125737
Homozygous LoFs: 0
Heterozygous LoFs: 11
Defined: 125748
p: 0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.57	177	246	0.719	0.0000162	2451
Missense (PolyPhen)		23	39.97	0.57544		460
Synonymous	0.998	71	82.5	0.860	0.00000438	758
Loss of Function	3.32	9	27.9	0.322	0.00000218	236

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000059	0.000058	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.000055	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000046	0.000044	rare
South Asian	0.000078	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: 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. The NELF complex is involved in HIV-1 latency possibly involving recruitment of PCF11 to paused RNA polymerase II. Provides the strongest RNA binding activity of the NELF complex and may initially recruit the NELF complex to RNA. Binds to the HIV-1 TAR RNA which is located in the long terminal repeat (LTR) of HIV-1. {ECO:0000269|PubMed:10199401, ECO:0000269|PubMed:11940650, ECO:0000269|PubMed:12612062, ECO:0000269|PubMed:18303858, ECO:0000269|PubMed:27282391, ECO:0000305}.;

Recessive Scores

pRec: 0.109

Intolerance Scores

RVIS EVS: -0.01
RVIS percentile EVS: 53.51

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): E

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium