ILDR1

Chr 3AR

immunoglobulin like domain containing receptor 1

Also known as: DFNB42, ILDR1alpha, ILDR1alpha', ILDR1beta

NCBI Gene: 286676 ENSG00000145103 UniProt: Q86SU0 OMIM: 609739

The ILDR1 protein maintains epithelial barrier function by recruiting tricellulin to tricellular tight junctions and is crucial for preserving the structural integrity of these junctions in auditory hair cells. Mutations cause autosomal recessive deafness (DFNB42), affecting hearing through disruption of inner ear epithelial barriers. The gene shows minimal constraint against loss-of-function variants (very low pLI score), consistent with its recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.061 OMIM phenotype

Clinical Summary— ILDR1

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Gene-Disease Validity (ClinGen)

nonsyndromic genetic hearing loss · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

35 unique Pathogenic / Likely Pathogenic· 175 VUS of 337 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.06LOEUF

pLI 0.000

Z-score 1.28

OE 0.75 (0.53–1.06)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.26Z-score

OE missense 1.04 (0.95–1.14)

347 obs / 333.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.75 (0.53–1.06)

0≤0.351.4

Missense OE?1.04 (0.95–1.14)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 22 / 29.5Missense obs/exp: 347 / 333.8Syn Z: -0.35

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveILDR1-related deafnessLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.75top 25%

GOF

0.6834th %ile

LOF

0.3647th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

337 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19

Likely Pathogenic16

VUS175

Likely Benign81

Benign21

Conflicting17

Pathogenic

Likely Pathogenic

175

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	18	1	0	0	19
Likely Pathogenic	14	2	0	0	16
VUS	1	167	6	1	175
Likely Benign	0	6	30	45	81
Benign	0	6	12	3	21
Conflicting	—				17
Total	33	182	48	49	329

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

19 pathogenic / likely-pathogenic (of 24) ClinVar copy-number / structural variants overlap ILDR1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →