NELFB

protein-coding

negative elongation factor complex member B, the group of Negative elongation factor complex members

Gene summary

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]).[supplied by OMIM, Mar 2008]

Previous symbols:

COBRA1

MANE transcript

NM_015456.5

Inheritance

—

ClinVar variants

U:93B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.35

Max pathogenic AF

—

Genomic locus

chr9:137,255,327-137,273,542

External References & Databases

Ensembl (ENSG00000188986)

Transcript & Mutation Effects

hg38 • Region Span ~18.2 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 NELFB variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 81

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015456.5. 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			4 clinvar	1 clinvar		5
missense			80 clinvar	1 clinvar		81
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			8 clinvar			8
Total	0	0	93	2	0	95

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015456.5	RefSeq	NP_056271.3	13	MANE Select
ENST00000343053.6	Ensembl	ENSP00000339495.6	13	MANE Select
ENST00001136993.1	Ensembl	ENSP00000807798.1	13	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

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

Gene / Model

Organism

Observed Phenotype

nelfb

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

Molecular Function

RNA binding
protein binding

Cellular Component

nucleoplasm
cytoplasm
NELF complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000343053
Coding exons: 13
Length: 18374
Individuals with no LoFs: 125724
Homozygous LoFs: 0
Heterozygous LoFs: 19
Defined: 125743
p: 0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.66	271	360	0.753	0.0000227	3751
Missense (PolyPhen)		85	128.05	0.6638		1340
Synonymous	-1.41	196	172	1.14	0.0000120	1188
Loss of Function	3.09	9	26.0	0.346	0.00000126	294

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00012	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0	0.0	absent
Other	0.00016	0.00016	rare

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. Binds RNA which may help to stabilize the NELF complex on nucleic acid. In vitro, binds weakly to the HIV-1 TAR RNA which is located in the long terminal repeat (LTR) of HIV-1. May be able to induce chromatin unfolding. {ECO:0000269|PubMed:10199401, ECO:0000269|PubMed:12612062, ECO:0000269|PubMed:23884411, ECO:0000269|PubMed:27282391}.;

Recessive Scores

pRec: 0.275

Intolerance Scores

RVIS EVS: -1.35
RVIS percentile EVS: 4.56

Essentials

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

Gene Damage Prediction

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