LRWD1

Chr 7

leucine rich repeats and WD repeat domain containing 1

Also known as: CENP-33, ORCA

The protein encoded by this gene interacts with components of the origin recognition complex (ORC) and regulates the formation of the prereplicative complex. The encoded protein stabilizes the ORC and therefore aids in DNA replication. This protein is required for the G1/S phase transition of the cell cycle. In addition, the encoded protein binds to trimethylated histone H3 in heterochromatin and recruits the ORC and lysine methyltransferases, which help maintain the repressive heterochromatic state. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

0
Active trials
18
Pathogenic / LP
147
ClinVar variants
2
Pubs (1 yr)
-0.2
Missense Z
1.31
LOEUF
Clinical SummaryLRWD1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
18 Pathogenic / Likely Pathogenic· 121 VUS of 147 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.31LOEUF
pLI 0.000
Z-score 0.16
OE 0.97 (0.731.31)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.23Z-score
OE missense 1.03 (0.951.12)
408 obs / 395.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.97 (0.731.31)
00.351.4
Missense OE1.03 (0.951.12)
00.61.4
Synonymous OE1.31
01.21.6
LoF obs/exp: 31 / 32.0Missense obs/exp: 408 / 395.2Syn Z: -3.30

ClinVar Variant Classifications

147 submitted variants in ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic2
VUS121
Likely Benign7
Benign1
16
Pathogenic
2
Likely Pathogenic
121
VUS
7
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
16
0
16
Likely Pathogenic
0
0
2
0
2
VUS
0
117
4
0
121
Likely Benign
0
6
0
1
7
Benign
0
1
0
0
1
Total0124221147

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

View in ClinVar →

LRWD1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence