IL12RB2

protein-coding

interleukin 12 receptor subunit beta 2, the group of Interleukin receptors|Fibronectin type III domain containing

Gene summary

The protein encoded by this gene is a type I transmembrane protein identified as a subunit of the interleukin 12 receptor complex. The coexpression of this and IL12RB1 proteins was shown to lead to the formation of high-affinity IL12 binding sites and reconstitution of IL12 dependent signaling. The expression of this gene is up-regulated by interferon gamma in Th1 cells, and plays a role in Th1 cell differentiation. The up-regulation of this gene is found to be associated with a number of infectious diseases, such as Crohn's disease and leprosy, which is thought to contribute to the inflammatory response and host defense. Several transcript variants encoding different isoforms and non-protein coding transcripts have been found for this gene. [provided by RefSeq, Apr 2012]

MANE transcript

NM_001374259.2

Inheritance

ClinVar variants

P:1U:396B:170

Top phenotype

IL12RB2-related disorder

gnomAD constraint

pLI —, LoF o/e 0.5

Max pathogenic AF

—

Genomic locus

chr1:67,307,364-67,398,724

External References & Databases

Ensembl (ENSG00000081985)

Transcript & Mutation Effects

hg38 • Region Span ~91.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

immunodeficiency diseaseLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0021094

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to IL12RB2 variants in ClinVar

4 Conditions Cataloged

not providedTotal: 597

not specifiedTotal: 147

IL12RB2-related disorderTotal: 28

Developmental delay, impaired speech, and behavioral abnormalities, with or without seizuresTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001374259.2. 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			3 clinvar	134 clinvar	4 clinvar	141
missense			356 clinvar	24 clinvar	6 clinvar	386
nonsense			10 clinvar	1 clinvar		11
start loss						0
frameshift			16 clinvar	1 clinvar		17
splice donor/acceptor (+/-2bp)		1 clinvar	11 clinvar			12
Total	0	1	396	160	10	567

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 47 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001374259.2	RefSeq	NP_001361188.1	15	MANE Select
ENST00000674203.2	Ensembl	ENSP00000501329.1	15	MANE Select
NM_001258214.1	RefSeq	NP_001245143.1	14	Standard
NM_001258215.1	RefSeq	NP_001245144.1	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Jak-STAT signaling pathway - Homo sapiens (human)
Inflammatory bowel disease (IBD) - Homo sapiens (human)
Th1 and Th2 cell differentiation - Homo sapiens (human)
Pathways in cancer - Homo sapiens (human)
Cytokine-cytokine receptor interaction - Homo sapiens (human)

Biological Process

cell surface receptor signaling pathway
positive regulation of cell population proliferation
peptidyl-tyrosine phosphorylation
response to lipopolysaccharide
interferon-gamma production

Molecular Function

cytokine receptor activity
protein kinase binding
cytokine binding

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: ENST00000262345
Coding exons: 15
Length: 89537
Individuals with no LoFs: 125645
Homozygous LoFs: 0
Heterozygous LoFs: 103
Defined: 125748
p: 0.000410

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.221	429	442	0.970	0.0000227	5647
Missense (PolyPhen)		97	106.54	0.91048		1396
Synonymous	-0.964	180	164	1.10	0.00000878	1679
Loss of Function	3.12	22	44.4	0.495	0.00000226	520

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00074	0.00074	rare
Latino/Admixed American	0.00029	0.00029	rare
Ashkenazi Jewish	0.00011	0.000099	rare
East Asian	0.00054	0.00054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00046	0.00046	rare
South Asian	0.00046	0.00046	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Receptor for interleukin-12. This subunit is the signaling component coupling to the JAK2/STAT4 pathway. Promotes the proliferation of T-cells as well as NK cells. Induces the promotion of T-cells towards the Th1 phenotype by strongly enhancing IFN-gamma production.;

Recessive Scores

pRec: 0.192

Intolerance Scores

LoFtool: 0.739
RVIS EVS: 0.96
RVIS percentile EVS: 90.19

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.231

Gene Damage Prediction

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