GIPC2

Chr 1

GIPC PDZ domain containing family member 2

Also known as: SEMCAP-2, SEMCAP2

The GIPC2 protein enables identical protein binding activity and is found in extracellular exosomes. This gene shows minimal constraint against loss-of-function variants (pLI near 0, LOEUF 1.59), and no definitive disease associations with GIPC2 mutations have been established in the provided data.

Summary from RefSeq
Research Assistant →
0
Active trials
5
Pubs (1 yr)
15
P/LP submissions
0%
P/LP missense
1.59
LOEUF
DN
Mechanism· predicted
Clinical SummaryGIPC2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
15 unique Pathogenic / Likely Pathogenic· 48 VUS of 69 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.59LOEUF
pLI 0.000
Z-score -0.03
OE 1.01 (0.661.59)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.27Z-score
OE missense 1.06 (0.941.20)
173 obs / 163.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.01 (0.661.59)
00.351.4
Missense OE1.06 (0.941.20)
00.61.4
Synonymous OE1.00
01.21.6
LoF obs/exp: 13 / 12.9Missense obs/exp: 173 / 163.3Syn Z: -0.00
DN
0.6842th %ile
GOF
0.6247th %ile
LOF
0.3647th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

69 submitted variants in ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic1
VUS48
Likely Benign1
14
Pathogenic
1
Likely Pathogenic
48
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
14
0
14
Likely Pathogenic
0
0
1
0
1
VUS
0
38
10
0
48
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total03925064

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

View in ClinVar →

Protein Context — Lollipop Plot

GIPC2 · 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.

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Clinical Literature
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