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…

Primary Disease Associations & Inheritance

Deafness, autosomal recessive 42MIM #609646

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · nonsyndromic genetic hearing loss · AR · ClinGen 2017

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.06

LOEUF

LOF

Mechanism· G2P

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

Background carrier burden — how many people carry a rare variant somewhere in ILDR1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 53

796 rare PASS variants

Rare truncating (LoF)

1 in 660

139 rare PASS variants

Rare synonymous (reference)

1 in 120

300 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ILDR1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 51	1 in 950
South Asian	~43k	1 in 44	1 in 550
Remaining (unassigned)	~30k	1 in 40	1 in 350
European (Finnish)	~27k	1 in 130	1 in 470
Admixed American	~22k	1 in 47	1 in 1,100
African / African American	~21k	1 in 43	1 in 760
East Asian	~20k	1 in 71	1 in 1,000
Ashkenazi Jewish	~13k	1 in 170	1 in 870
Middle Eastern	~2,884	1 in 44	1 in 570

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 8 coding exons well covered in gnomAD exomes and genomes.? see exons ↓