IL27RA

protein-coding

interleukin 27 receptor subunit alpha, the group of Interleukin receptors|Fibronectin type III domain containing

Gene summary

In mice, CD4+ helper T-cells differentiate into type 1 (Th1) cells, which are critical for cell-mediated immunity, predominantly under the influence of IL12. Also, IL4 influences their differentiation into type 2 (Th2) cells, which are critical for most antibody responses. Mice deficient in these cytokines, their receptors, or associated transcription factors have impaired, but are not absent of, Th1 or Th2 immune responses. This gene encodes a protein which is similar to the mouse T-cell cytokine receptor Tccr at the amino acid level, and is predicted to be a glycosylated transmembrane protein. [provided by RefSeq, Jul 2008]

MANE transcript

NM_004843.4

Inheritance

ClinVar variants

U:92B:14

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.64

Max pathogenic AF

—

Genomic locus

chr19:14,031,762-14,053,218

External References & Databases

Ensembl (ENSG00000104998)

Transcript & Mutation Effects

hg38 • Region Span ~21.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Epstein-Barr virus infectionMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0005111

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to IL27RA variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 95

not providedTotal: 8

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004843.4. 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	2 clinvar	5
missense			87 clinvar	9 clinvar	1 clinvar	97
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	92	11	3	106

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004843.4	RefSeq	NP_004834.1	14	MANE Select
ENST00000263379.4	Ensembl	ENSP00000263379.1	14	MANE Select
ENST00000855328.1	Ensembl	ENSP00000525387.1	14	Standard
ENST00000855328.2	Ensembl	ENSP00000525387.1	14	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Jak-STAT signaling pathway - Homo sapiens (human)
Th17 cell differentiation - Homo sapiens (human)
JAK-STAT-Core
Interleukin-12 family signaling
Signaling by Interleukins

Biological Process

positive regulation of T-helper 1 type immune response
negative regulation of type 2 immune response
immune response
cell surface receptor signaling pathway
positive regulation of interferon-gamma production

Molecular Function

transmembrane signaling receptor activity
cytokine receptor activity
cytokine binding
interleukin-27 receptor activity

Cellular Component

plasma membrane
integral component of plasma membrane
external side of plasma membrane
receptor complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000263379
Coding exons: 14
Length: 21184
Individuals with no LoFs: 125629
Homozygous LoFs: 0
Heterozygous LoFs: 119
Defined: 125748
p: 0.000473

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.12	310	371	0.836	0.0000209	4022
Missense (PolyPhen)		41	72.644	0.5644		899
Synonymous	1.14	139	157	0.885	0.00000941	1357
Loss of Function	2.03	24	37.4	0.642	0.00000199	360

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.00044	0.00043	rare
Ashkenazi Jewish	0.0052	0.0047	notable
East Asian	0.00027	0.00027	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00035	0.00033	rare
South Asian	0.00031	0.00029	rare
Other	0.00035	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Receptor for IL27. Requires IL6ST/gp130 to mediate signal transduction in response to IL27. This signaling system acts through STAT3 and STAT1. Involved in the regulation of Th1- type immune responses. Also appears to be involved in innate defense mechanisms. {ECO:0000269|PubMed:14764690}.;

Recessive Scores

pRec: 0.194

Intolerance Scores

LoFtool: 0.873
RVIS EVS: -0.09
RVIS percentile EVS: 47.12

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.904

Gene Damage Prediction

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