IL31RA

interleukin 31 receptor A, the group of Interleukin receptors|Fibronectin type III domain containing

Basic information

Region (hg38): 5:55851356-55922854

Links

ENSG00000164509 ∙ NCBI:133396 ∙ OMIM:609510 ∙ HGNC:18969 ∙ Uniprot:Q8NI17 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• amyloidosis, primary localized cutaneous, 2 (Limited), mode of inheritance: AD
• familial primary localized cutaneous amyloidosis (Supportive), mode of inheritance: AD
• amyloidosis, primary localized cutaneous, 2 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Amyloidois, primary localized cutaneous, 2	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Dermatologic	19663869; 19690585

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IL31RA gene.

• Inborn genetic diseases (25 variants)
• not provided (10 variants)
• Amyloidosis, primary localized cutaneous, 2 (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IL31RA gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2	5	7
missense			20	2	2	24
nonsense						0
start loss			1			1
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			1	1	3	5
Total	0	0	22	5	10

Variants in IL31RA

This is a list of pathogenic ClinVar variants found in the IL31RA region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-55851603-G-C		IL31RA-related disorder	Likely benign (Jun 06, 2019)
5-55851624-G-A			Benign/Likely benign (Feb 01, 2024)
5-55851629-A-G			Uncertain significance (-)
5-55853555-C-T			Likely benign (Nov 01, 2022)
5-55859560-C-G		not specified	Uncertain significance (Mar 07, 2024)
5-55859574-C-T		Amyloidosis, primary localized cutaneous, 2	Benign (Aug 19, 2021)
5-55859576-C-T			Benign (Jun 18, 2018)
5-55868872-A-G		not specified	Uncertain significance (Jan 22, 2024)
5-55872304-A-G		IL31RA-related disorder	Benign (Feb 26, 2019)
5-55872398-A-T		not specified	Uncertain significance (Jun 03, 2022)
5-55872424-A-G		not specified	Uncertain significance (Jan 04, 2022)
5-55872429-A-G			Benign (Mar 09, 2018)
5-55883136-C-T		not specified	Uncertain significance (Feb 15, 2023)
5-55883163-C-T		not specified	Uncertain significance (Nov 12, 2021)
5-55883205-G-T		IL31RA-related disorder	Likely benign (Sep 17, 2019)
5-55883224-A-T		Amyloidosis, primary localized cutaneous, 2	Benign (Aug 19, 2021)
5-55890071-G-A			Benign (Dec 31, 2019)
5-55890072-G-A		IL31RA-related disorder • not specified	Conflicting classifications of pathogenicity (Apr 05, 2023)
5-55890098-C-A		not specified	Uncertain significance (May 23, 2023)
5-55896341-T-C		IL31RA-related disorder	Benign (Jan 02, 2020)
5-55896381-G-A		IL31RA-related disorder	Likely benign (Apr 08, 2019)
5-55896395-C-A		not specified	Uncertain significance (Jan 22, 2024)
5-55896395-C-T		not specified	Likely benign (Jun 12, 2023)
5-55896396-G-A			Likely benign (Feb 01, 2023)
5-55896407-G-A		not specified	Uncertain significance (Jul 26, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IL31RA	protein_coding	protein_coding	ENST00000447346	15	71472

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.20e-16	0.273	125680	0	68	125748	0.000270

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.824	353	399	0.884	0.0000219	5015
Missense in Polyphen		37	61.091	0.60566		826
Synonymous	-0.404	155	149	1.04	0.00000880	1435
Loss of Function	1.38	29	38.2	0.759	0.00000202	446

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000394	0.000394
Ashkenazi Jewish	0.00	0.00
East Asian	0.000326	0.000326
Finnish	0.000416	0.000416
European (Non-Finnish)	0.000283	0.000281
Middle Eastern	0.000326	0.000326
South Asian	0.000294	0.000294
Other	0.000655	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Associates with OSMR to form the interleukin-31 receptor which activates STAT3 and to a lower extent STAT1 and STAT5 (PubMed:11877449, PubMed:14504285, PubMed:15627637, PubMed:15194700). May function in skin immunity (PubMed:15184896). Mediates IL31-induced itch, probably in a manner dependent on cation channels TRPA1 and TRPV1 (By similarity). Positively regulates numbers and cycling status of immature subsets of myeloid progenitor cells in bone marrow in vivo and enhances myeloid progenitor cell survival in vitro (By similarity). {ECO:0000250|UniProtKB:Q8K5B1, ECO:0000269|PubMed:11877449, ECO:0000269|PubMed:14504285, ECO:0000269|PubMed:15184896, ECO:0000269|PubMed:15194700, ECO:0000269|PubMed:15627637}.
• Disease: DISEASE: Amyloidosis, primary localized cutaneous, 2 (PLCA2) [MIM:613955]: A primary amyloidosis characterized by localized cutaneous amyloid deposition. This condition usually presents with itching (especially on the lower legs) and visible changes of skin hyperpigmentation and thickening that may be exacerbated by chronic scratching and rubbing. Primary localized cutaneous amyloidosis is often divided into macular and lichen subtypes although many affected individuals often show both variants coexisting. Lichen amyloidosis characteristically presents as a pruritic eruption of grouped hyperkeratotic papules with a predilection for the shins, calves, ankles and dorsa of feet and thighs. Papules may coalesce to form hyperkeratotic plaques that can resemble lichen planus, lichen simplex or nodular prurigo. Macular amyloidosis is characterized by small pigmented macules that may merge to produce macular hyperpigmentation, sometimes with a reticulate or rippled pattern. In macular and lichen amyloidosis, amyloid is deposited in the papillary dermis in association with grouped colloid bodies, thought to represent degenerate basal keratinocytes. The amyloid deposits probably reflect a combination of degenerate keratin filaments, serum amyloid P component, and deposition of immunoglobulins. {ECO:0000269|PubMed:19690585}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: JAK-STAT-Core (Consensus)

Recessive Scores

• pRec: 0.239

Intolerance Scores

• loftool: 0.917
• rvis_EVS: 0.65
• rvis_percentile_EVS: 84.15

Haploinsufficiency Scores

• pHI: 0.0522
• hipred: N
• hipred_score: 0.123

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.444

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Il31ra
• Phenotype: homeostasis/metabolism phenotype; hematopoietic system phenotype; skeleton phenotype; immune system phenotype

Gene ontology

• Biological process: MAPK cascade;glandular epithelial cell differentiation;acute inflammatory response to antigenic stimulus;defense response;transmembrane receptor protein tyrosine kinase signaling pathway;JAK-STAT cascade;positive regulation of cell population proliferation;cytokine-mediated signaling pathway;monocyte differentiation;macrophage differentiation;T-helper 2 cell cytokine production;positive regulation of tyrosine phosphorylation of STAT protein;homeostatic process;negative regulation of macrophage activation;negative regulation of apoptotic process;positive regulation of transcription, DNA-templated;defense response to other organism
• Cellular component: plasma membrane;external side of plasma membrane;integral component of membrane;cell junction;axon;presynaptic membrane;receptor complex
• Molecular function: transcription coactivator activity;cytokine receptor activity;protein kinase binding;cytokine binding