ROR1

Chr 1AR

receptor tyrosine kinase like orphan receptor 1

Also known as: NTRKR1, dJ537F10.1

The protein is a receptor tyrosine kinase-like orphan receptor that modulates neurite growth in the central nervous system and is crucial for spiral ganglion neurons to innervate auditory hair cells in the inner ear. Mutations cause autosomal recessive deafness (deafness, autosomal recessive 108). The gene is highly constrained against loss-of-function variants (pLI = 0.996, LOEUF = 0.267), indicating that complete loss of protein function is likely pathogenic.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

?Deafness, autosomal recessive 108MIM #617654
AR
1
Active trials
81
Pubs (1 yr)
23
P/LP submissions
0%
P/LP missense
0.27
LOEUF· LoF intol.
Mechanism
Clinical SummaryROR1
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Gene-Disease Validity (ClinGen)
nonsyndromic genetic hearing loss · ARLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
23 unique Pathogenic / Likely Pathogenic· 188 VUS of 318 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.27LOEUF
pLI 0.996
Z-score 4.79
OE 0.12 (0.060.27)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.17Z-score
OE missense 0.73 (0.670.80)
373 obs / 511.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.12 (0.060.27)
00.351.4
Missense OE0.73 (0.670.80)
00.61.4
Synonymous OE0.90
01.21.6
LoF obs/exp: 4 / 34.3Missense obs/exp: 373 / 511.2Syn Z: 1.09

ClinVar Variant Classifications

318 submitted variants in ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic1
VUS188
Likely Benign55
Benign24
Conflicting1
22
Pathogenic
1
Likely Pathogenic
188
VUS
55
Likely Benign
24
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
22
0
22
Likely Pathogenic
0
0
1
0
1
VUS
2
175
11
0
188
Likely Benign
0
3
9
43
55
Benign
0
1
14
9
24
Conflicting
1
Total21795752291

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

View in ClinVar →

Protein Context — Lollipop Plot

ROR1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Literature
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