IL17RD

interleukin 17 receptor D, the group of Interleukin receptors|TIR domain containing

Basic information

Region (hg38): 3:57089981-57170306

Links

ENSG00000144730 ∙ NCBI:54756 ∙ OMIM:606807 ∙ HGNC:17616 ∙ Uniprot:Q8NFM7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Kallmann syndrome (Supportive), mode of inheritance: AD
• hypogonadotropic hypogonadism 18 with or without anosmia (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypogonadotropic hypogonadism 18, with or without anosmia	AD/Digenic	Audiologic/Otolaryngologic; Endocrine	In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required; Congenital hearing loss in individuals is typically (though not always) described as unilateral, and recognition and interventions related to speech and language development may be beneficial	Audiologic/Otolaryngologic; Dental; Endocrine; Musculoskeletal; Neurologic	23643382
Relatively complex genetic models of disease have been described (eg, involving variants in other FGF8-network-associated genes)

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IL17RD gene.

• not provided (111 variants)
• Inborn genetic diseases (36 variants)
• not specified (6 variants)
• Hypogonadotropic hypogonadism 18 with or without anosmia (5 variants)
• Delayed puberty (3 variants)
• Cerebral arteriovenous malformation (2 variants)
• Hypogonadotropic hypogonadism 18 with anosmia (1 variants)
• Hypogonadism (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IL17RD 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				25	4	29
missense		1	57	5	5	68
nonsense		1	1			2
start loss			1			1
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region			1			1
non coding			1	19	23	43
Total	0	2	62	49	32

Highest pathogenic variant AF is 0.0000657

Variants in IL17RD

This is a list of pathogenic ClinVar variants found in the IL17RD region.

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

Position	Type	Phenotype	Significance	ClinVar
3-57096401-GGGCGACCGC-G			Uncertain significance (Nov 09, 2023)
3-57096404-C-T			Uncertain significance (Jan 01, 2024)
3-57096405-G-A		not specified	Likely benign (Feb 15, 2022)
3-57096409-G-A		HYPOGONADOTROPIC HYPOGONADISM 18 WITH ANOSMIA, SUSCEPTIBILITY TO • IL17RD-related disorder	Uncertain significance (Feb 09, 2024)
3-57096475-T-C		not specified	Uncertain significance (Mar 01, 2024)
3-57096501-C-G		not specified	Uncertain significance (Mar 06, 2023)
3-57096501-C-T			Likely benign (Aug 28, 2022)
3-57096615-TA-T			Benign (Aug 30, 2018)
3-57096631-C-T			Benign (Dec 24, 2018)
3-57096633-C-T			Likely benign (Oct 21, 2018)
3-57097501-A-C			Benign (Aug 09, 2018)
3-57097612-G-A			Likely benign (Mar 02, 2023)
3-57097625-G-A			Uncertain significance (Nov 22, 2023)
3-57097629-G-A			Likely benign (Jul 07, 2023)
3-57097655-G-A		not specified	Uncertain significance (Apr 12, 2022)
3-57097670-A-T		not specified	Uncertain significance (Mar 07, 2024)
3-57097684-C-A		not specified	Uncertain significance (Apr 22, 2022)
3-57097686-C-T		not specified	Uncertain significance (Sep 29, 2022)
3-57097691-G-A			Likely benign (Dec 31, 2019)
3-57097694-G-A		not specified	Uncertain significance (May 06, 2023)
3-57097717-T-C		IL17RD-related disorder	Likely benign (Apr 20, 2020)
3-57097725-G-A			Uncertain significance (Jun 25, 2022)
3-57097731-T-C		IL17RD-related disorder	Benign/Likely benign (May 18, 2022)
3-57097735-C-A		IL17RD-related disorder	Likely benign (Jul 01, 2019)
3-57097757-G-A			Uncertain significance (Jan 15, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IL17RD	protein_coding	protein_coding	ENST00000296318	13	80325

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000105	0.999	125572	0	37	125609	0.000147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.278	415	431	0.962	0.0000264	4795
Missense in Polyphen		108	112.74	0.95796		1338
Synonymous	0.0166	191	191	0.998	0.0000136	1431
Loss of Function	3.01	16	35.3	0.453	0.00000192	406

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000305	0.000301
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000556	0.0000544
Finnish	0.0000471	0.0000462
European (Non-Finnish)	0.000198	0.000194
Middle Eastern	0.0000556	0.0000544
South Asian	0.000165	0.000163
Other	0.000168	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Feedback inhibitor of fibroblast growth factor mediated Ras-MAPK signaling and ERK activation. May inhibit FGF-induced FGFR1 tyrosine phosphorylation. Regulates the nuclear ERK signaling pathway by spatially blocking nuclear translocation of activated ERK without inhibiting cytoplasmic phosphorylation of ERK. Mediates JNK activation and may be involved in apoptosis. Might have a role in the early stages of fate specification of GnRH-secreting neurons (By similarity). {ECO:0000250, ECO:0000269|PubMed:12807873, ECO:0000269|PubMed:12958313, ECO:0000269|PubMed:15239952}.
• Pathway: IL17 signaling pathway;Pathways Affected in Adenoid Cystic Carcinoma;MAP2K and MAPK activation;Signal Transduction;EGFR1;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;FGF signaling pathway (Consensus)

Recessive Scores

• pRec: 0.124

Intolerance Scores

• loftool: 0.690
• rvis_EVS: -0.17
• rvis_percentile_EVS: 40.63

Haploinsufficiency Scores

• pHI: 0.675
• hipred: Y
• hipred_score: 0.619
• ghis: 0.492

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.242

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Il17rd
• Phenotype: cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; normal phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; immune system phenotype

Zebrafish Information Network

• Gene name: il17rd
• Affected structure: posterior lateral line primordium
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: MAPK cascade;cytokine-mediated signaling pathway
• Cellular component: Golgi membrane;nucleoplasm;Golgi apparatus;plasma membrane;integral component of membrane
• Molecular function: interleukin-17 receptor activity