WDR7

Chr 18

WD repeat domain 7

Also known as: TRAG

The protein forms the beta subunit of rabconnectin-3 and regulates calcium-dependent exocytosis of neurotransmitters by controlling Rab3 small G proteins. Mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability, seizures, and movement abnormalities. This gene is highly constrained against loss-of-function variants in the general population.

Summary from RefSeq
Research Assistant →
0
Active trials
6
Pubs (1 yr)
68
P/LP submissions
0%
P/LP missense
0.18
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryWDR7
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.
📋
ClinVar Variants
66 unique Pathogenic / Likely Pathogenic· 180 VUS of 280 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.18LOEUF
pLI 1.000
Z-score 7.44
OE 0.10 (0.060.18)
Highly constrained

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

Missense Constraint
2.48Z-score
OE missense 0.76 (0.710.81)
639 obs / 841.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.10 (0.060.18)
00.351.4
Missense OE0.76 (0.710.81)
00.61.4
Synonymous OE0.96
01.21.6
LoF obs/exp: 8 / 79.6Missense obs/exp: 639 / 841.8Syn Z: 0.50
DN
0.3793th %ile
GOF
0.4184th %ile
LOF
0.75top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.18

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

280 submitted variants in ClinVar

Classification Summary

Pathogenic64
Likely Pathogenic2
VUS180
Likely Benign7
Benign5
64
Pathogenic
2
Likely Pathogenic
180
VUS
7
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
64
0
64
Likely Pathogenic
0
0
2
0
2
VUS
1
172
7
0
180
Likely Benign
0
3
0
4
7
Benign
0
0
1
4
5
Total1175748258

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

View in ClinVar →

Protein Context — Lollipop Plot

WDR7 · 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
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗