IL7

protein-coding

interleukin 7, the group of Interleukins

Gene summary

The protein encoded by this gene is a cytokine important for B and T cell development. This cytokine and the hepatocyte growth factor (HGF) form a heterodimer that functions as a pre-pro-B cell growth-stimulating factor. IL7 is found to be a cofactor for V(D)J rearrangement of the T cell receptor beta (TCRB) during early T cell development. This cytokine can be produced locally by intestinal epithelial and epithelial goblet cells, and may serve as a regulatory factor for intestinal mucosal lymphocytes. IL7 plays an essential role in lymphoid cell survival, and in the maintenance of naive and memory T cells. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional splice variants have been described but their presence in normal tissues has not been confirmed. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can be a potent inducer of proinflammatory cytokines and chemokines which may defend against the infection, but may also mediate destructive lung injury. Elevated serum IL7 levels, together with several other circulating cytokines and chemokines, has been found to be associated with the severity of Coronavirus Disease 19 (COVID-19). [provided by RefSeq, Jul 2020]

MANE transcript

NM_000880.4

Inheritance

ClinVar variants

P:3U:22B:4

Top phenotype

Immunodeficiency 130 with HPV-related verrucosis

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr8:78,675,743-78,805,523

External References & Databases

Ensembl (ENSG00000104432)

Transcript & Mutation Effects

hg38 • Region Span ~129.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

epidermodysplasia verruciformisSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009176

Submitter: Orphanet

immunodeficiency 130 with HPV-related verrucosisLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0032667

Submitter: G2P

combined immunodeficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0015131

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Immunodeficiency 130 with HPV-related verrucosisAR

Manifestation: Allergy/Immunology/Infectious; Dermatologic; Oncologic

Intervention: Allergy/Immunology/Infectious; Oncologic

Rationale: Individuals have been described with susceptibility to certain infections as well as potential increased risk of skin cancer, and awareness may allow prompt diagnosis and management of sequeleae

Refs: 25981006

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to IL7 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 22

Epidermodysplasia verruciformis, susceptibility to, 5Total: 5

IL7-related disorderTotal: 4

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000880.4. 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	2 clinvar		3
missense			19 clinvar	1 clinvar	1 clinvar	21
nonsense	1 clinvar					1
start loss	1 clinvar					1
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	3	0	22	3	1	29

Highest pathogenic variant AF is 6.8473264e-7

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 24 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000880.4	RefSeq	NP_000871.1	6	MANE Select
ENST00000263851.9	Ensembl	ENSP00000263851.4	6	MANE Select
NM_001199886.2	RefSeq	NP_001186815.1	5	Standard
NM_001199887.2	RefSeq	NP_001186816.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

PI3K-Akt signaling pathway - Homo sapiens (human)
Jak-STAT signaling pathway - Homo sapiens (human)
Pathways in cancer - Homo sapiens (human)
Hematopoietic cell lineage - Homo sapiens (human)
Cytokine-cytokine receptor interaction - Homo sapiens (human)

Biological Process

positive regulation of cytokine-mediated signaling pathway
T cell lineage commitment
humoral immune response
cell-cell signaling
positive regulation of cell population proliferation

Molecular Function

cytokine activity
interleukin-7 receptor binding
protein binding
growth factor activity

Cellular Component

extracellular region
extracellular space
collagen-containing extracellular matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000263851
Coding exons: 6
Length: 129781
Individuals with no LoFs: 125294
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 125295
p: 0.00000399

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.705	67	85.3	0.785	0.00000400	1178
Missense (PolyPhen)		9	20.084	0.44812		310
Synonymous	0.372	27	29.6	0.913	0.00000134	299
Loss of Function	2.67	0	8.31	0.00	3.48e-7	120

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Hematopoietic growth factor capable of stimulating the proliferation of lymphoid progenitors. It is important for proliferation during certain stages of B-cell maturation.;

Recessive Scores

pRec: 0.496

Intolerance Scores

LoFtool: 0.140
RVIS EVS: 0.21
RVIS percentile EVS: 67.72

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.903

Gene Damage Prediction

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