THSD7A

Chr 7

thrombospondin type 1 domain containing 7A

NCBI Gene: 221981ENSG00000005108UniProt: Q9UPZ6

Plays a role in actin cytoskeleton rearrangement

172
ClinVar variants
1
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— THSD7A
⚡
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
1 Pathogenic / Likely Pathogenic· 166 VUS of 172 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.21LOEUF
pLI 1.000
Z-score 8.06
OE 0.14 (0.09–0.21)
Highly constrained

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

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.60Z-score
OE missense 1.06 (1.00–1.11)
947 obs / 896.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.14 (0.09–0.21)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.06 (1.00–1.11)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.22
0≤1.21.6
LoF obs/exp: 14 / 101.7Missense obs/exp: 947 / 896.6Syn Z: -3.11

ClinVar Variant Classifications

172 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1
VUS166
Likely Benign5
1
Pathogenic
166
VUS
5
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
1
0
1
Likely Pathogenic
0
0
0
0
0
VUS
0
165
1
0
166
Likely Benign
0
3
0
2
5
Benign
0
0
0
0
0
Total016822172

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

View in ClinVar →

Protein Context — Lollipop Plot

THSD7A · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Primary Membranous Nephropathy.
Couser WG·Clin J Am Soc Nephrol
2017Review
Membranous Nephropathy: Core Curriculum 2021.
Alsharhan L et al.·Am J Kidney Dis
2021Review
Mechanisms of Primary Membranous Nephropathy.
Gu Y et al.·Biomolecules
2021Review
New 'Antigens' in Membranous Nephropathy.
Sethi S·J Am Soc Nephrol
2021Review
Membranous nephropathy: new pathogenic mechanisms and their clinical implications.
Hoxha E et al.·Nat Rev Nephrol
2022Review
Membranous nephropathy-diagnosis and identification of target antigens.
Sethi S et al.·Nephrol Dial Transplant
2024Review
Antigens in membranous nephropathy: discovery and clinical implications.
Sethi S et al.·Nat Rev Nephrol
2025Review
Autoantibody-triggered podocyte membrane budding drives autoimmune kidney disease.
Lahme K et al.·Cell
2026
Segmental membranous nephropathy.
Choung HYG et al.·Clin Exp Nephrol
2021Review
Dual-antigen membranous nephropathy.
Nasr SH et al.·Kidney Int
2026
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools