ILDR1

protein-coding

immunoglobulin like domain containing receptor 1

Gene summary

This gene encodes a protein that contains an immunoglobulin-like domain. The encoded protein may function as a multimeric receptor at the cell surface. The expression of this gene may be a diagnostic marker for cancer progression. Alternatively spliced transcript variants encoding multiple protein isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

Previous symbols:

DFNB42

MANE transcript

NM_001199799.2

Inheritance

ClinVar variants

P:43U:189B:74

Top phenotype

Deafness, autosomal recessive 42

gnomAD constraint

pLI —, LoF o/e 0.75

Max pathogenic AF

—

Genomic locus

chr3:121,987,323-122,022,247

External References & Databases

Ensembl (ENSG00000145103)

Transcript & Mutation Effects

hg38 • Region Span ~34.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

nonsyndromic genetic hearing lossDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0019497

Submitter: ClinGen

The ILDR1 gene has been associated with autosomal recessive nonsyndromic hearing loss using the ClinGen Clinical Validity Framework as of 10/20/2017. This association was made using case-level data and experimental data. At least 13 variants (missense, nonsense, frameshift, splice site) have been reported in humans. ILDR1 was first associated with this disease in humans as early as 2011 (Borck et al.). Association is seen in at least 15 probands in 4 publications (21255762, 23226338, 22903915, 27344577). Variants in this gene segregated with disease in more than 4 additional family members. More evidence is available in the literature, but the maximum score for genetic evidence and experimental evidence (18 pts.) has been reached. The mechanism for disease is biallelic LOF (21255762, 23226338, 22903915, 27344577, 25819842, 24990150). This gene-disease association is supported by mouse and zebrafish models as well as expression and protein interaction studies (21255762, 23239027, 25822906, 25819842, 24990150). In summary, ILDR1 is definitively associated with autosomal recessive nonsyndromic hearing loss. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Hearing Loss Working Group on 11/21/2017.

autosomal recessive nonsyndromic hearing loss 42DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0012326

Submitter: G2P

autosomal recessive nonsyndromic hearing loss 42STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012326

Submitter: Labcorp Genetics (formerly Invitae)

hearing loss, autosomal recessiveSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0019588

Submitter: Orphanet

autosomal recessive nonsyndromic hearing loss 42STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012326

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Deafness, autosomal recessive 42AR

Manifestation: Audiologic/Otolaryngologic

Intervention: Audiologic/Otolaryngologic

Rationale: Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development

Refs: 15641023; 21255762; 23226338

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ILDR1 variants in ClinVar

14 Conditions Cataloged

not providedTotal: 223

Inborn genetic diseasesTotal: 97

not specifiedTotal: 68

Autosomal recessive nonsyndromic hearing loss 42Total: 46

ILDR1-related disorderTotal: 41

ILDR1-related disordersTotal: 9

Hearing loss, autosomal recessiveTotal: 5

Hearing impairmentTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001199799.2. 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			2 clinvar	53 clinvar	1 clinvar	56
missense	1 clinvar	2 clinvar	185 clinvar	15 clinvar	5 clinvar	208
nonsense	7 clinvar	10 clinvar				17
start loss	1 clinvar	1 clinvar				2
frameshift	7 clinvar	14 clinvar	1 clinvar			22
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	16	27	189	68	6	306

Highest pathogenic variant AF is 0.00017511881

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 30 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001199799.2	RefSeq	NP_001186728.1	8	MANE Select
ENST00000344209.10	Ensembl	ENSP00000345667.5	8	MANE Select
NM_001199800.2	RefSeq	NP_001186729.1	6	Standard
NM_175924.4	RefSeq	NP_787120.1	7	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
ildr1b	Danio rerio	Structure: posterior lateral line primordium Quality: disorganized abnormal

Gene / Model

Organism

Observed Phenotype

ildr1b

Danio rerio

Structure: posterior lateral line primordium

Quality: disorganized

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

receptor-mediated endocytosis
protein homooligomerization
positive regulation of peptide hormone secretion
cellular response to leukemia inhibitory factor

Molecular Function

identical protein binding
high-density lipoprotein particle receptor activity

Cellular Component

cytosol
plasma membrane
integral component of membrane
protein-containing complex
tricellular tight junction

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000344209
Coding exons: 8
Length: 34882
Individuals with no LoFs: 125666
Homozygous LoFs: 0
Heterozygous LoFs: 82
Defined: 125748
p: 0.000326

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.256	347	334	1.04	0.0000211	3528
Missense (PolyPhen)		138	141.32	0.9765		1484
Synonymous	-0.350	137	132	1.04	0.00000758	1093
Loss of Function	1.28	22	29.5	0.746	0.00000173	291

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.00031	0.00030	rare
East Asian	0.00022	0.00022	rare
Finnish	0.00051	0.00051	rare
European (Non-Finnish)	0.00033	0.00033	rare
South Asian	0.00059	0.00059	rare
Other	0.00066	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Putative membrane receptor.;

Recessive Scores

pRec: 0.0989

Intolerance Scores

LoFtool: 0.951
RVIS EVS: -0.02
RVIS percentile EVS: 52.28

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0624

Gene Damage Prediction

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